Glossary of Terms

A way for one gene to make different versions of a protein.

Alternative splicing allows a single gene to be used in multiple ways, producing different RNA and protein forms depending on how its exons are combined. This is especially important in the brain. Reduced HNRNPC can disturb alternative splicing in many other brain-related genes.

A pattern where one changed copy of a gene is enough to cause a condition.

Autosomal dominant inheritance means that having a variant in just one of the two copies of a gene can be sufficient to cause a condition. If a parent has an autosomal dominant HNRNPC variant, each child has a 50% chance of inheriting it. However, many HNRNPC cases are de novo, with no prior family history.

Also known as: ADHD-like symptoms

Challenges with focusing, sitting still, or controlling impulses.

Attention difficulties can include trouble concentrating, restlessness, and impulsivity. Some individuals with HNRNPC-related RNDD show attention-deficit/hyperactivity disorder (ADHD)–like features and may benefit from behavioral strategies, school accommodations, and in some cases medication.

Also known as: Petit mal seizures

Brief seizures causing staring spells and loss of awareness.

Absence seizures are a type of seizure that causes a brief lapse in awareness, often appearing as a staring spell that lasts only a few seconds. The person may blink rapidly or make small movements but does not fall or convulse. After the seizure, they typically resume normal activity with no memory of the episode. Absence seizures are most common in children.

An irregularly shaped cornea or lens causing blurred vision.

Astigmatism is a common refractive error caused by an irregular curvature of the cornea (the clear front surface of the eye) or the lens inside the eye. Instead of being round like a basketball, the eye is shaped more like a football, which causes light to focus at multiple points rather than one, resulting in blurred or distorted vision at all distances. Astigmatism is easily corrected with glasses or contact lenses.

Also known as: Aortic root enlargement, Dilated aortic root

Enlargement of the first portion of the aorta where it connects to the heart.

Aortic root dilation is a condition in which the aortic root, the portion of the aorta that connects directly to the heart, becomes abnormally enlarged. This can increase the risk of aortic valve problems and aortic dissection. Regular monitoring with echocardiography may be recommended for individuals with known aortic root dilation.

Also known as: ASD, Hole in the heart

A hole in the wall between the two upper chambers of the heart.

An atrial septal defect (ASD) is a congenital heart defect in which there is a hole in the septum (wall) that divides the two upper chambers (atria) of the heart. This allows oxygen-rich blood from the left atrium to mix with oxygen-poor blood in the right atrium. Small ASDs may close on their own or cause no symptoms, while larger ones may require surgical repair.

Also known as: Cerebellar ataxia, Coordination problems

A lack of muscle coordination affecting movement, balance, and speech.

Ataxia refers to a group of disorders affecting coordination, balance, and speech. It is caused by damage to or dysfunction of the cerebellum, the part of the brain that controls movement coordination. People with ataxia may have difficulty with walking, hand movements, eye movements, and speech. Ataxia can be present from birth in genetic conditions or develop over time due to various causes.

Also known as: ASD, Autism, Autistic traits

A developmental condition affecting social communication and behavior.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by differences in social communication and interaction, along with restricted and repetitive patterns of behavior, interests, or activities. The term 'spectrum' reflects the wide variation in challenges and strengths possessed by each person with autism. ASD is frequently observed in individuals with HNRNP-related disorders and other genetic conditions affecting brain development.

Also known as: Attention deficit hyperactivity disorder, Attention difficulties, Hyperactivity

A neurodevelopmental disorder affecting attention, impulse control, and activity levels.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental condition characterized by persistent patterns of inattention, hyperactivity, and impulsivity that interfere with functioning or development. Symptoms may include difficulty focusing, trouble staying organized, fidgeting, excessive talking, and acting without thinking. ADHD is commonly observed in children with genetic neurodevelopmental conditions.

Also known as: Speech apraxia, Dyspraxia of speech, Childhood apraxia of speech, CAS

A motor speech disorder affecting the ability to coordinate movements needed for speech.

Apraxia of speech is a motor speech disorder in which the brain has difficulty coordinating the muscle movements necessary for speech. The person knows what they want to say, but their brain has trouble planning and sequencing the movements required to produce the words. In children, this is called childhood apraxia of speech (CAS). It is different from muscle weakness and requires specialized speech therapy.

Also known as: Almond eyes

Eyes with an elongated, oval shape resembling an almond.

Almond-shaped eyes describe an eye shape that is elongated and tapers at both the inner and outer corners, resembling the shape of an almond. While this is a normal variation in many populations, it is also noted as a characteristic facial feature in certain genetic conditions. Clinicians may note this feature as part of a comprehensive physical examination.

Also known as: AKS, HNRNPK-related disorder

A rare genetic condition caused by variants in the HNRNPK gene affecting development.

Au-Kline syndrome (AKS) is a rare genetic condition caused by changes in the HNRNPK gene. It affects how a child grows, learns, and develops. Children with this condition almost always have low muscle tone, developmental delays, and learning differences. Many also share recognizable facial features, and some have heart, kidney, or bone differences. The condition is named after the researchers who first described it.

Also known as: Dysautonomia, Autonomic nervous system dysfunction

Problems with the automatic body functions like sweating and temperature regulation.

Autonomic dysfunction refers to problems with the autonomic nervous system, which controls automatic body functions like heart rate, blood pressure, sweating, digestion, and temperature regulation. Symptoms can include difficulty regulating body temperature, abnormal sweating, constipation, and other digestive issues. Many children with HNRNP disorders may experience some degree of autonomic dysfunction.

Also known as: Nasal alae, Nostrils

The outer flared parts of the nose forming the nostrils.

The alae nasi (singular: ala nasi) are the lateral cartilaginous wings of the nose that form the sides of the nostrils. In clinical descriptions, terms like 'thick alae nasi' or 'hypoplastic alae nasi' may be used to describe variations in the size or shape of these structures. Thicker or broader alae nasi may be noted as a facial feature in certain genetic conditions.

Also known as: ASM, Anticonvulsant, Antiepileptic drug, AED

Medications used to prevent or reduce the occurrence of seizures.

Anti-seizure medications (ASMs) are drugs used to prevent or reduce the frequency and severity of seizures in people with epilepsy. There are many different ASMs, and the choice of medication depends on the type of seizures, age, other health conditions, and potential side effects. Some individuals may need multiple medications or combinations to achieve good seizure control.

Also known as: AAC, Alternative communication

Methods and tools that help people communicate when speech is difficult.

Augmentative and alternative communication (AAC) encompasses various methods, devices, and strategies that support or replace spoken communication for individuals who have difficulty speaking. AAC can range from low-tech options like picture boards and sign language to high-tech devices with speech-generating capabilities. For many individuals with HNRNPU-NDD who have limited or no speech, AAC can significantly improve their ability to communicate and express their needs and thoughts.

Also known as: Short fingers, Short toes

Unusually short fingers or toes.

Brachydactyly refers to fingers or toes that are shorter than typical due to shortened bones. There are several types, depending on which bones are affected. Brachydactyly is usually a minor physical finding and typically does not cause significant functional problems.

Also known as: Flat head syndrome

A head shape that is wider and shorter from front to back.

Brachycephaly describes a head shape that is proportionally wider and shorter than typical, often appearing somewhat flattened at the back. It can result from positioning (positional brachycephaly) or from early fusion of skull bones (craniosynostosis). Mild positional brachycephaly is common and usually improves on its own.

Also known as: Narrow eye openings

Abnormally narrow horizontal eye openings.

Blepharophimosis refers to an eyelid condition where the horizontal opening of the eyes is narrower than typical. This can give the appearance of smaller eyes. It is often present from birth and can occur as part of certain genetic syndromes. The condition may affect vision if severe, and surgical correction is sometimes considered.

Also known as: Split tongue, Grooved tongue

A tongue that appears split, grooved, or divided.

A bifid tongue is a tongue that appears split, deeply grooved, or divided, either partially or along its full length. This can range from a mild groove to a more pronounced division. In Au-Kline syndrome, some individuals may have a large or deeply grooved tongue that sometimes appears split or bifid. This feature may affect feeding in infancy but often does not cause long-term problems.

Also known as: Split uvula, Cleft uvula

A uvula that is split or divided into two parts.

A bifid uvula is a minor variation where the uvula (the small tissue that hangs down at the back of the throat) is split or divided into two parts. It is often considered a mild form of cleft palate and may be associated with submucous cleft palate. A bifid uvula is usually discovered incidentally and typically does not cause significant problems, though it may be associated with certain genetic conditions.

Also known as: Inflexibility, Rigid thinking

Difficulty adapting to changes in routine or unexpected situations.

Behavioral rigidity refers to difficulty being flexible with routines, rules, or expectations. Children with behavioral rigidity may become upset when plans change, insist on doing things in a particular way, or struggle to transition between activities. This is commonly seen in children with autism spectrum disorder and can be addressed through behavioral strategies and therapies.

Also known as: CNV

A change where a stretch of DNA is missing or duplicated.

Copy number variants are deletions or duplications of larger sections of DNA that may include one or more genes. When a CNV affects HNRNPC, it can reduce the number of working copies of the gene and lead to similar symptoms as smaller variants.

Also known as: CLIP-seq, eCLIP

A method to find where RNA-binding proteins attach to RNA.

CLIP sequencing is a set of techniques that allow researchers to see which RNA molecules a particular RNA-binding protein, such as HNRNPC, physically binds to. Enhanced CLIP (eCLIP) provides high-resolution maps of these binding sites, helping to identify downstream target genes.

The thick band of nerve fibers connecting the two halves of the brain.

The corpus callosum is a large bundle of nerve fibers that connects the left and right hemispheres of the brain, allowing them to communicate. Some individuals are born with an absent (agenesis), thin (hypoplasia), or abnormally shaped corpus callosum. This can affect how the brain processes information and may be associated with developmental challenges.

A finger that curves sideways, usually the pinky finger.

Clinodactyly is a condition in which a finger, most commonly the fifth finger (pinky), curves to the side rather than growing straight. It results from abnormal development of the finger bones. Clinodactyly is usually a minor finding that does not affect hand function and can occur on its own or as part of various genetic conditions.

Also known as: Ocular coloboma

A gap or notch in part of the eye from incomplete development.

A coloboma is a gap or missing piece in one of the structures of the eye, such as the iris, retina, or optic nerve. It occurs when the eye does not close completely during fetal development. Colobomas can vary in size and location, and their effect on vision depends on which part of the eye is involved.

A small eye combined with a gap in eye structures.

Colobomatous microphthalmia is a condition in which the eye is both abnormally small (microphthalmia) and has a coloboma (a gap in one of the eye structures). This combination occurs when eye development is significantly disrupted during early pregnancy. The impact on vision varies depending on the size of the eye and the location of the coloboma.

The strip of tissue that separates the nostrils.

The columella is the fleshy tissue at the base of the nose that separates the two nostrils. Variations in its appearance, such as a long or hanging columella, can be observed in some genetic conditions as a minor facial feature difference.

The part of the brain that controls balance and coordination.

The cerebellum is located at the back of the brain, below the cerebrum. It plays a key role in coordinating voluntary movements, balance, posture, and motor learning. Abnormalities in the cerebellum can lead to difficulties with coordination, balance, and fine motor skills.

The narrow middle part of the cerebellum.

The cerebellar vermis is the narrow, central region of the cerebellum that connects its two hemispheres. It plays an important role in coordinating movements of the trunk and legs and in maintaining balance. Anomalies of the cerebellar vermis, such as hypoplasia (underdevelopment), can be associated with coordination difficulties and are seen in some neurodevelopmental conditions.

Also known as: Bent finger

A finger that is permanently bent at the middle joint.

Camptodactyly is a condition in which one or more fingers are bent at the middle joint and cannot be fully straightened. It most commonly affects the fifth finger (pinky). The condition is usually present from birth or develops during childhood and may be mild or more pronounced. It can occur on its own or as part of various genetic conditions.

A decrease in the size of the cerebellum over time.

Cerebellar atrophy refers to the progressive loss of neurons and tissue in the cerebellum, the part of the brain responsible for coordinating movement and balance. This can lead to problems with coordination, balance, walking, and fine motor skills. Cerebellar atrophy can be seen on brain MRI and may be caused by various genetic or acquired conditions.

Also known as: CVI, Cerebral visual impairment

A vision problem caused by the brain's inability to process visual information.

Cortical visual impairment (CVI) is a visual impairment caused by problems in the brain rather than the eyes. The eyes may be healthy and function normally, but the brain has difficulty interpreting and processing visual information. CVI is one of the leading causes of visual impairment in children and can range from mild to severe. It is often associated with neurological conditions and brain abnormalities.

Also known as: CP

A group of disorders affecting movement and muscle tone caused by brain damage.

Cerebral palsy is a group of permanent movement disorders that appear in early childhood and are caused by abnormal development or damage to the parts of the brain that control movement, balance, and posture. It can cause stiff muscles (spasticity), uncontrolled movements, and problems with coordination. The severity varies widely from mild to severe, and it may be associated with other neurological conditions.

Also known as: Cupid's bow lip, Exaggerated Cupid's bow

The double curve of the upper lip resembling the bow of Cupid.

The Cupid's bow refers to the shape of the upper lip border, which typically has a double curve resembling the bow of the mythological figure Cupid. In some genetic conditions, including Au-Kline syndrome, the Cupid's bow may be more pronounced or exaggerated, giving the upper lip a wide 'M' shape. This is one of several facial features that may be noted during clinical evaluation.

Also known as: Undescended testicles, Undescended testes

A condition where one or both testicles have not descended into the scrotum.

Cryptorchidism is a condition in which one or both testicles fail to descend from the abdomen into the scrotum before birth or during the first few months of life. It is one of the most common genital abnormalities in male infants. If the testicle does not descend on its own, surgery (orchiopexy) is typically performed to move it into the scrotum, usually during the first year of life.

Also known as: Palatoschisis

An opening or split in the roof of the mouth.

A cleft palate is a birth difference where there is an opening or split in the roof of the mouth (palate). It occurs when the tissue that makes up the roof of the mouth does not join completely during pregnancy. Cleft palate can affect feeding, speech development, and hearing. Treatment typically involves surgery to close the opening, often performed in the first year of life, along with speech therapy and other supportive care.

Also known as: Early skull fusion

A condition where skull bones fuse together too early.

Craniosynostosis is a birth defect in which one or more of the joints (sutures) between the bones of a baby's skull close prematurely, before the brain is fully formed. This can cause problems with normal brain and skull growth, leading to an abnormally shaped head. Depending on which sutures are affected and how severely, treatment may involve surgery to allow the brain room to grow normally.

Also known as: CHD, Heart defect, Congenital heart disease

A heart problem present at birth.

Congenital heart defects are structural problems with the heart that are present from birth. They can affect the heart walls, valves, or blood vessels. CHDs range from simple (like small holes in the heart that may close on their own) to complex conditions requiring surgery. Many genetic conditions, including Au-Kline syndrome, are associated with an increased risk of congenital heart defects, making cardiac screening important.

Also known as: Agenesis of the corpus callosum, ACC

A condition where the corpus callosum fails to develop.

Agenesis of the corpus callosum (ACC) is a condition present from birth in which the corpus callosum, the bundle of nerve fibers connecting the two hemispheres of the brain, fails to develop partially or completely. This can occur as an isolated finding or as part of various genetic syndromes. The effects can range from mild to significant, affecting learning, behavior, and coordination. Some individuals with ACC have few symptoms while others may have more significant developmental challenges.

Also known as: Arnold-Chiari malformation, Chiari I malformation

A condition where brain tissue extends into the spinal canal.

Chiari malformation is a condition in which brain tissue, specifically part of the cerebellum, extends below the skull into the upper spinal canal. This occurs when part of the skull is too small or misshapen, pressing on the brain and pushing it downward. Chiari malformation can cause headaches, neck pain, balance problems, and other neurological symptoms. Severity ranges from asymptomatic to requiring surgical treatment.

A new genetic change that appears for the first time in a child.

A de novo variant is a genetic change that is not present in either parent but arises in the egg, sperm, or early embryo. Many individuals with HNRNPC-related RNDD have de novo variants, meaning the condition was not inherited but started with them.

A branching extension of a neuron that receives signals.

Dendrites are tree-like branches extending from neurons that receive input from other brain cells. The shape and number of dendrites influence how well neurons can communicate. Reduced or altered dendritic growth has been observed when HNRNPC levels are not properly balanced in model systems.

A pediatrician who specializes in child development and behavior.

Developmental pediatricians focus on developmental delays, learning differences, and behavioral challenges. They can help coordinate care, recommend therapies, and support school planning for children with HNRNPC-related RNDD.

Also known as: Hypomyelination

Slower-than-expected coating of nerve fibers in the brain.

Delayed myelination occurs when the insulating coating around nerve fibers develops more slowly than typical. This can be seen on brain MRI, where certain areas may appear different than expected for a child's age. Delayed myelination may contribute to developmental delays, though many children show improvement over time as myelination progresses.

Also known as: Distal underdevelopment

Underdevelopment of the end parts of limbs, such as fingers or toes.

Distal hypoplasia refers to the incomplete development or underdevelopment of the distal (end) portions of body parts, particularly the fingers and toes. This can affect the size, shape, or structure of these body parts and may be present from birth as part of various genetic conditions.

Also known as: Difficulty swallowing, Swallowing disorder

Difficulty or discomfort when swallowing food or liquids.

Dysphagia is a condition characterized by difficulty or discomfort when swallowing. It can affect the ability to safely swallow food, liquids, or saliva, and may increase the risk of choking or aspiration (food entering the airway). Dysphagia can result from problems with the muscles or nerves involved in swallowing and may require modified diets, therapy, or in some cases, tube feeding.

Also known as: Dystonic movements

A movement disorder causing sustained muscle contractions and abnormal postures.

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions that cause repetitive movements, abnormal postures, or both. The movements are often twisting and may affect a single body part (focal dystonia) or multiple areas (generalized dystonia). Dystonia can occur on its own or as a symptom of various neurological and genetic conditions.

Also known as: Regression, Skill loss

Loss of previously acquired developmental skills.

Developmental regression refers to the loss of skills or abilities that a child had previously acquired, such as language, motor skills, or social abilities. This can be particularly distressing for families. Regression can occur in various neurodevelopmental conditions and may happen suddenly or gradually. The specific pattern and timing of regression can sometimes help identify the underlying cause.

Also known as: Skill plateau

A period where developmental progress slows or stops without losing skills.

A developmental plateau refers to a period during which a child's acquisition of new developmental skills significantly slows or temporarily stops, without the loss of previously gained skills. Unlike regression, the child maintains their current abilities but does not progress as expected. Plateaus may be followed by periods of renewed skill acquisition.

Also known as: Methylation, Epigenetic modification

Chemical markers on DNA that affect how genes are turned on or off.

DNA methylation is a type of chemical modification where methyl groups are added to DNA molecules. This 'chemical tagging' affects how genes are expressed without changing the DNA sequence itself. Some genetic conditions, including Au-Kline syndrome, have distinctive DNA methylation patterns (called episignatures) that can be detected through blood testing and help confirm a diagnosis, especially when genetic testing results are uncertain.

Also known as: DEE

A condition where both development and brain function are affected by epileptic activity.

Developmental and epileptic encephalopathy (DEE) describes conditions where developmental delays are present (sometimes even before seizures begin) and are worsened by epileptic activity. The term recognizes that both the underlying genetic cause and the seizures contribute to developmental challenges. HNRNPU-related disorder is classified as DEE54, indicating it is the 54th genetic cause identified in this category.

Also known as: MAE, Myoclonic-astatic epilepsy

A childhood epilepsy syndrome with myoclonic-atonic seizures.

Doose syndrome, also known as myoclonic-astatic epilepsy (MAE), is a type of childhood epilepsy characterized by myoclonic-atonic seizures where a brief muscle jerk is followed by sudden loss of muscle tone, causing falls. It typically begins in previously healthy children between ages 2-5 years. Some children with Doose syndrome respond well to treatment and have a good developmental outcome, while others may have ongoing challenges.

Also known as: Long head, Scaphocephaly

A head shape that is longer and narrower than typical.

Dolichocephaly describes a head shape that is proportionally longer from front to back and narrower from side to side than typical. The head appears elongated when viewed from above. It can result from positioning in the womb or during infancy, or from early fusion of certain skull sutures (craniosynostosis). Mild dolichocephaly is often a normal variation that does not cause health problems.

A coding piece of a gene that is kept in the final RNA message.

Exons are the segments of a gene that remain after splicing and are joined together to form the final RNA code used to build a protein. Changes in how exons are included or skipped can alter the resulting protein's structure and function.

A condition where a person has repeated, unprovoked seizures.

Epilepsy is diagnosed when someone has more than one unprovoked seizure over time. Not all individuals with HNRNPC-related RNDD have epilepsy, but for those who do, medications and neurological care can help manage seizures.

Services for young children with developmental delays, often started before age 3.

Early intervention programs provide therapy and support services during the first years of life, when the brain is especially adaptable. Starting early intervention after an HNRNPC-related RNDD diagnosis can help children develop important skills as soon as possible.

Also known as: Electroencephalogram, Electroencephalography

A test that records electrical activity in the brain.

An electroencephalogram (EEG) is a medical test that measures and records electrical activity in the brain using small electrodes attached to the scalp. It is commonly used to diagnose and monitor epilepsy and seizure disorders, as well as other brain conditions. EEG abnormalities can indicate underlying neurological issues even when seizures are not actively occurring.

Also known as: Atopic dermatitis, Dermatitis

A condition causing itchy, inflamed, and irritated skin.

Eczema, also called atopic dermatitis, is a chronic skin condition characterized by dry, itchy, and inflamed skin. It often appears as red, scaly patches and can occur anywhere on the body. Eczema is common in children and often runs in families, particularly those with allergies or asthma. Treatment typically includes moisturizers, avoiding triggers, and sometimes medicated creams.

Also known as: DNA methylation signature, Methylation signature

A distinctive pattern of DNA methylation associated with a specific condition.

An episignature is a unique pattern of DNA methylation that is characteristic of a specific genetic condition. These patterns can be detected through specialized blood tests and serve as a diagnostic biomarker. Episignatures are particularly useful for confirming diagnoses when genetic variants are of uncertain significance or when clinical features are mild. Au-Kline syndrome has a well-established episignature that helps confirm the diagnosis.

Also known as: EE

A severe type of epilepsy where frequent seizures contribute to brain dysfunction.

Epileptic encephalopathy refers to a group of severe epilepsy syndromes in which frequent seizures and abnormal electrical activity in the brain contribute to cognitive and developmental difficulties beyond what would be expected from the underlying cause alone. The seizure activity itself appears to worsen brain function. Early and effective seizure control is important to try to minimize developmental impact.

A DNA change that shifts the reading frame of a gene.

A frameshift variant occurs when DNA bases are added or removed in a way that shifts the 'reading frame' of the gene. This usually leads to a completely altered and often nonfunctional protein, often with an early stop signal.

Also known as: Dysmorphic features

Subtle differences in facial appearance that can be seen in some genetic conditions.

Some genetic conditions are associated with characteristic facial appearances. In HNRNPC-related RNDD, reported features are generally mild and may include a thin upper lip, smooth philtrum (the groove between nose and upper lip), or other subtle traits. These differences do not affect a child's abilities or personality.

Also known as: Prominent fingertip pads, Persistent fetal pads

Soft, rounded padding on the fingertips that persists after birth.

Fetal fingertip pads are soft, fleshy pads on the tips of the fingers that are normally present in developing fetuses. In most people, these pads flatten out before or shortly after birth. When they remain prominent, they are called persistent fetal fingertip pads and can be a minor physical finding in some genetic conditions, including HNRNPC-related RNDD.

Also known as: Soft spot, Fontanel

The soft spots on a baby's head where skull bones have not yet fused.

Fontanelles are soft, membrane-covered gaps between the bones of an infant's skull. The most noticeable is the anterior fontanelle at the top of the head. These spaces allow the skull to be flexible during birth and accommodate rapid brain growth in early life. They gradually close as the skull bones fuse, typically by 12–18 months of age. A large fontanelle may close later than expected.

Also known as: FTT

When a child does not gain weight or grow as expected.

Failure to thrive describes a pattern in which a child's weight or growth rate is significantly below what is expected for their age. It can result from feeding difficulties, absorption problems, increased calorie needs, or underlying medical conditions. Early identification and supportive interventions such as feeding therapy and nutritional support can help improve outcomes.

Also known as: Fever seizures

Seizures triggered by fever, most common in young children.

Febrile seizures are convulsions or seizures that occur in young children (typically between 6 months and 5 years of age) in association with a fever. They are usually brief and do not cause lasting harm. While frightening for parents, simple febrile seizures do not typically indicate epilepsy, though children with certain genetic conditions may have a higher risk of developing epilepsy later.

Also known as: Thick lower lip, Prominent lower lip

A lower lip that appears fuller or more prominent than average.

A full lower lip is a facial feature where the lower lip appears thicker or more prominent. While this is a normal variation in facial features, it may be noted by clinicians as part of a pattern of distinctive features associated with certain genetic conditions. It is typically observed alongside other facial characteristics during clinical evaluation.

Also known as: Prominent forehead

A forehead that appears unusually prominent or protrudes forward.

Frontal bossing refers to a forehead that appears more prominent than typical, often protruding forward. It can be associated with various genetic conditions or may occur as part of normal variation. Frontal bossing itself does not cause health problems but is noted during physical examination as it may be part of a recognizable pattern of features associated with certain conditions.

Also known as: mutation, DNA change

A change in the DNA sequence of a gene.

A genetic variant is any difference in the DNA sequence compared with the typical sequence. Some variants are harmless, while others can affect how a gene works. Disease-causing variants in HNRNPC can change the amount or function of the HNRNPC protein.

The genetic makeup of an individual, specifically the variants present in their DNA.

Genotype refers to the specific set of genetic variants a person carries, typically for a particular gene or set of genes. For example, knowing someone's genotype for HNRNPK means knowing which specific DNA variant they have in that gene. The genotype is what is inherited and can be identified through genetic testing.

Also known as: genotype-phenotype relationship

The relationship between specific genetic variants and the observable features they cause.

Genotype-phenotype correlation describes how specific genetic variants (genotype) relate to the medical and developmental features seen in individuals (phenotype). For example, in Au-Kline syndrome, researchers have found that individuals with loss-of-function variants often have more heart and kidney complications, while those with missense variants may have milder medical involvement. Understanding these correlations helps predict outcomes and guide clinical care.

Also known as: GDD

Delays in reaching multiple early milestones, such as motor, speech, and learning skills.

Global developmental delay describes children who are slower than expected to reach a range of milestones across several areas, including movement, language, problem-solving, and social skills. It is one of the most common early signs in HNRNPC-related RNDD.

Also known as: Whole genome sequencing, WGS

A test that reads almost all of a person's DNA.

Genome sequencing analyzes nearly the entire DNA sequence, including exons, introns, and regions between genes. It can detect variants that may be missed by more targeted tests and is increasingly used when conditions like HNRNPC-related RNDD are suspected but not yet explained.

A healthcare professional who explains genetic conditions and testing.

Genetic counselors are trained to help families understand complex genetic information, testing options, and what a diagnosis means for medical care and family planning. They are valuable partners for families affected by HNRNPC-related RNDD.

Seizures that affect both sides of the brain at once.

Generalized seizures are seizures that involve both hemispheres of the brain from the start. They can take various forms, including tonic-clonic seizures (with muscle stiffening and jerking), absence seizures (staring spells), or myoclonic seizures (brief muscle jerks). Generalized seizures may cause loss of consciousness and can vary in severity.

Also known as: GERD, Reflux, Acid reflux

When stomach contents flow back up into the esophagus.

Gastroesophageal reflux occurs when stomach acid and contents flow backward from the stomach into the esophagus (the tube connecting the mouth to the stomach). This can cause discomfort, spitting up, and sometimes feeding difficulties. Many infants have some reflux, but persistent or severe reflux may require dietary changes, positioning strategies, or medication.

Also known as: Gonadal mosaicism

A condition where a genetic change exists in some egg or sperm cells of a parent.

Germline mosaicism occurs when a parent has a genetic variant in some of their egg or sperm cells but not in their other body cells. This means the parent may not show signs of the condition, yet can still pass the variant to their children. Germline mosaicism explains how some de novo (new) genetic conditions can occasionally recur in siblings, even when neither parent appears to carry the variant in their blood.

Also known as: Gastrostomy tube, Feeding tube, PEG tube

A tube placed through the abdomen directly into the stomach for feeding.

A gastrostomy tube (G-tube) is a tube inserted through the abdomen directly into the stomach to provide nutrition, fluids, or medications when a person cannot eat or drink enough by mouth. It may be placed when there are swallowing difficulties, failure to thrive, or aspiration risk. G-tubes can be temporary or long-term and allow individuals to receive adequate nutrition while protecting the airway.

Also known as: Growth hormone, GH therapy, Human growth hormone

Treatment with synthetic growth hormone to promote growth.

Growth hormone therapy involves daily injections of synthetic human growth hormone to treat children who are not growing at normal rates due to various causes, including genetic conditions. It can help increase height and improve body composition. The decision to use growth hormone therapy is made carefully by endocrinologists after thorough evaluation of the underlying cause of poor growth.

Also known as: Heterogeneous nuclear ribonucleoprotein C

A gene that helps cells process RNA, especially in the brain.

HNRNPC is a gene that provides instructions for making a protein involved in RNA processing and regulation. It helps the cell correctly edit and prepare RNA messages before they are used to make proteins. Because the brain depends heavily on precise RNA control during development, changes in HNRNPC can affect how the brain grows and functions.

Also known as: HNRNPC-RNDD, HNRNPC-related RNDD

A genetic condition caused by changes in the HNRNPC gene that affect brain development.

HNRNPC-related neurodevelopmental disorder is a genetic condition in which changes (variants) in one copy of the HNRNPC gene lead to challenges in development, learning, and behavior. Children may show global developmental delay, intellectual disability, speech and motor delays, low muscle tone, and sometimes seizures or sleep and attention difficulties.

When one working copy of a gene is not enough for normal function.

Haploinsufficiency occurs when a person has one normal copy and one non-working or partially working copy of a gene, and the single healthy copy does not produce enough protein for typical function. In HNRNPC-related RNDD, the problem appears to be that the level of HNRNPC protein is too low, not that it is entirely absent.

Also known as: Low muscle tone

Reduced muscle tone, making the body feel floppy or less firm.

Hypotonia is a condition where muscles have less tension than usual. Children with hypotonia may feel floppy when held and may take longer to develop motor skills. Many individuals with HNRNPC-related RNDD have low muscle tone, especially in early childhood.

A nonprofit organization dedicated to families affected by HNRNP-related conditions.

The HNRNP Family Foundation supports families living with HNRNPC-related RNDD and other HNRNP-related disorders. It focuses on education, community-building, advocacy, and promoting research aimed at better treatments and quality of life.

Also known as: High palate

A roof of the mouth that is more arched than typical.

A high-arched palate refers to the roof of the mouth being more curved or dome-shaped than usual. This anatomical variation can occur on its own or as part of certain genetic conditions. While often a minor finding, a very high palate may occasionally contribute to feeding difficulties in infancy or speech articulation differences.

A birth difference where the urethral opening is not at the tip of the penis.

Hypospadias is a congenital condition in males where the opening of the urethra (the tube that carries urine out of the body) is located on the underside of the penis rather than at the tip. It is one of the most common birth differences affecting males and can often be corrected with surgery, typically in early childhood.

Also known as: Hammer toe, Hammertoe deformity

A toe deformity where the toe bends downward at the middle joint.

Hammertoe is a foot deformity in which one or more toes become bent at the middle joint, causing them to curl downward instead of pointing forward. This can cause pain, calluses, and difficulty wearing shoes. Hammertoes can develop due to muscle imbalances, nerve problems, or as part of various genetic conditions affecting muscle tone and development.

Also known as: Swollen kidney, Dilated kidney

Swelling of the kidney due to urine not draining properly.

Hydronephrosis is a condition where one or both kidneys become swollen because urine cannot drain properly from the kidney to the bladder. It can be detected before birth on prenatal ultrasound or discovered later in life. The severity ranges from mild to severe, and treatment depends on the underlying cause. Hydronephrosis is commonly seen in several genetic conditions, including Au-Kline syndrome.

Also known as: Pain insensitivity, Decreased pain sensitivity

Reduced sensitivity to painful stimuli.

High pain tolerance refers to a reduced response to painful stimuli, where an individual may not react as expected to injuries or painful medical procedures. This can be concerning as it may delay recognition of illness or injury. High pain tolerance is observed in some individuals with neurodevelopmental conditions and may be related to differences in sensory processing or autonomic nervous system function.

Also known as: Heterogeneous nuclear ribonucleoprotein U, hnRNP U

A gene that encodes an important DNA- and RNA-binding protein.

HNRNPU is a gene located on chromosome 1q44 that provides instructions for making heterogeneous nuclear ribonucleoprotein U. This protein plays multiple essential roles including nuclear chromatin organization, telomere-length regulation, mRNA alternative splicing and stability, and mitotic cell cycle regulation. It is expressed strongly in the cerebellum and fetal brain. Changes in HNRNPU can cause HNRNPU-related neurodevelopmental disorder.

Also known as: HNRNPU-NDD, HNRNPU-RNDD, DEE54, Developmental and epileptic encephalopathy 54

A genetic condition caused by changes in the HNRNPU gene affecting brain development.

HNRNPU-related neurodevelopmental disorder is a genetic condition caused by changes (variants) in the HNRNPU gene. It is characterized by developmental delay and intellectual disability – typically moderate to severe – with speech and language delay. Most affected individuals have seizures, often beginning before age 2. Other features may include hypotonia, feeding difficulties, behavioral issues, and nonspecific dysmorphic features.

Also known as: High muscle tone, Increased muscle tone, Muscle rigidity

Abnormally high muscle tone causing stiffness.

Hypertonia refers to abnormally increased muscle tone, causing muscles to feel stiff or rigid. It can make movement difficult and may lead to contractures (permanent tightening) if not managed. While many children with HNRNPU-NDD initially have hypotonia (low muscle tone), some may develop hypertonia over time, which can lead to spasticity. Physical therapy is important for managing tone abnormalities.

Also known as: Hyperopia, Farsightedness, Far-sightedness, Long-sightedness

A vision condition where close objects appear blurry.

Hypermetropia, commonly called farsightedness, is a refractive error in which distant objects may be seen more clearly than close objects. It occurs when the eyeball is too short or the cornea has too little curvature, causing light to focus behind the retina rather than on it. Hypermetropia is very common and is easily corrected with glasses, contact lenses, or surgery.

A non-coding piece of a gene that is usually removed during splicing.

Introns are sequences in a gene that are transcribed into RNA but then removed during the splicing process. While introns themselves do not code for protein, their presence and removal are tightly regulated, and errors in this process can disrupt normal gene expression.

A small deletion in a gene that removes amino acids but keeps the reading frame intact.

An in-frame deletion is a genetic change where a small number of DNA bases is deleted in multiples of three, so the overall reading frame of the gene is preserved. The resulting protein is shorter but not completely disrupted. In HNRNPC, a recurring in-frame deletion has been found to reduce the amount of HNRNPC protein.

Also known as: ID

Lifelong challenges with learning and everyday reasoning skills.

Intellectual disability involves limitations in intellectual functioning (such as reasoning, problem-solving, and learning) and in adaptive behavior (everyday life skills). In HNRNPC-related RNDD, intellectual disability can range from mild to severe, and many children benefit from tailored educational support.

Also known as: IEP

A customized school plan for students with special educational needs.

An IEP is a legally binding document in many school systems that outlines a student's learning goals and the supports, accommodations, and services they will receive. Children with HNRNPC-related RNDD who qualify can use an IEP to get tailored help in school.

Also known as: Hypermobile joints, Double-jointed

Joints that move beyond the normal range of motion.

Joint hypermobility refers to joints that can extend beyond the typical range of motion, sometimes called being 'double-jointed.' While many people with hypermobile joints have no problems, some may experience joint pain, dislocations, or fatigue. Joint hypermobility can occur on its own or as part of various genetic conditions affecting connective tissue.

A research method that partially reduces the level of a gene's protein.

Knockdown refers to experimental techniques that lower, but do not completely remove, the amount of a protein produced by a gene. In HNRNPC research, knockdown mimics haploinsufficiency and helps scientists understand how reduced HNRNPC affects neurons.

Also known as: Keto diet for epilepsy

A high-fat, low-carbohydrate diet used to help control seizures.

The ketogenic diet is a specialized high-fat, adequate-protein, low-carbohydrate diet that has been used since the 1920s to help control seizures, particularly in children whose seizures do not respond well to medications. The diet changes how the body uses energy, producing ketones that may help reduce seizure activity. It requires careful medical supervision and monitoring by a dietitian.

Also known as: LoF variant

A DNA change that reduces or eliminates the function of a gene.

Loss-of-function variants are changes in DNA that prevent the gene from making a fully working protein. This can happen through early stop signals, large deletions, or severe disruptions of the gene's structure. Many HNRNPC variants appear to act by reducing how much functioning protein is available.

Also known as: LGS

A severe form of childhood epilepsy with multiple seizure types.

Lennox-Gastaut syndrome (LGS) is a severe form of epilepsy that typically begins in early childhood. It is characterized by multiple types of seizures that are often difficult to control, cognitive impairment, and a specific abnormal EEG pattern. Children with LGS may have tonic (stiffening), atonic (drop), and atypical absence seizures. It can develop from West syndrome or other causes.

A DNA change that swaps one building block of a protein for another.

A missense variant is a single DNA change that results in one amino acid (protein building block) being replaced by another. Depending on where this happens in the protein, it may have little effect or significantly alter the protein's shape or function.

Slower development of movement skills like sitting, walking, or using hands.

Motor delay refers to a child reaching physical milestones such as rolling, sitting, crawling, walking, or using their hands later than typical. Both fine (small movements) and gross (large movements) motor skills can be affected in HNRNPC-related RNDD.

Also known as: MRI, Brain MRI

A scan that uses magnets to create detailed pictures of the brain.

MRI is a non-invasive imaging technique that provides detailed views of the brain's structure. In some individuals with HNRNPC-related RNDD, brain MRI may show differences in brain size or structure, while in others it may appear typical.

A laboratory mouse that carries a genetic change similar to a human condition.

Mouse models are used in research to study how specific genetic changes affect development and behavior. By altering HNRNPC levels in mice, scientists can observe effects on brain development and test potential therapies in the future.

Also known as: Myelin

The process of coating nerve fibers to help signals travel faster.

Myelination is the process by which nerve fibers in the brain and nervous system become coated with myelin, a fatty substance that acts like insulation on electrical wires. Proper myelination allows nerve signals to travel quickly and efficiently. Delayed myelination means this coating process is slower than expected, which can affect development.

Also known as: Metacarpal bones

The five long bones in the palm of the hand.

The metacarpals are the five long bones that make up the palm of the hand, connecting the wrist to the fingers. Differences in metacarpal size or shape, such as small or shortened metacarpals, can be a minor skeletal finding in some genetic conditions.

Also known as: Metatarsus varus

A foot shape where the front part curves inward.

Metatarsus adductus is a common foot condition in which the front half of the foot turns inward. It is often noticed at birth and may result from positioning in the womb. Many cases improve on their own or with stretching exercises, though some may require casting or other treatment.

Also known as: Small head

A head size that is smaller than expected for age and sex.

Microcephaly means the head circumference is significantly smaller than average for a child's age and sex. It can be present at birth (congenital) or develop later. Microcephaly may indicate that the brain is smaller than expected, which can be associated with developmental differences. The degree of impact varies widely depending on the underlying cause.

Also known as: Large head

A head size that is larger than expected for age and sex.

Macrocephaly means the head circumference is significantly larger than average for a child's age and sex. It can be a normal family trait or may be associated with certain medical conditions. In some cases, macrocephaly is related to increased fluid in the brain or to differences in brain growth.

Also known as: Nearsightedness, Near-sightedness

A vision condition where distant objects appear blurry.

Myopia, commonly called nearsightedness, is a refractive error in which close objects can be seen clearly but distant objects appear blurry. It occurs when the eyeball is too long or the cornea has too much curvature. Myopia is very common and is easily corrected with glasses, contact lenses, or surgery.

Also known as: Microphthalmos, Small eye

An eye that is abnormally small.

Microphthalmia is a condition in which one or both eyes are abnormally small. The degree can range from mildly reduced size to severely underdeveloped. Vision in the affected eye may be reduced or absent, depending on severity. Microphthalmia can occur alone or with other eye abnormalities such as coloboma.

A genetic condition affecting the macula and central vision.

Macular dystrophy is a group of inherited eye disorders that affect the macula, the central part of the retina responsible for sharp, detailed vision. These conditions typically cause progressive loss of central vision while peripheral (side) vision usually remains intact. The age of onset and rate of progression vary depending on the specific type.

Also known as: Mitral valve abnormalities

Structural or functional differences in the heart's mitral valve.

Mitral valve anomalies refer to various structural or functional abnormalities of the mitral valve, which separates the left atrium and left ventricle of the heart. These can include mitral valve prolapse (where the valve bulges back into the atrium), regurgitation (leaking), or stenosis (narrowing). Mitral valve anomalies may require monitoring or treatment depending on their severity.

A condition that affects how the brain grows and functions over time.

A neurodevelopmental disorder is a condition that begins early in life and affects how the brain develops. It can influence learning, movement, speech, behavior, and social skills. Neurodevelopmental disorders are lifelong, but supportive therapies and accommodations can greatly improve quality of life.

Also known as: Nerve cell

A cell that carries messages in the brain and nervous system.

Neurons are specialized brain cells that send and receive signals. They connect to each other through long branches and junctions called synapses. Proper growth, branching, and connection of neurons are essential for learning, memory, and behavior. HNRNPC plays a role in how neurons develop and connect.

The process by which young brain cells move to their correct positions.

During brain development, immature neurons must move from where they are born to their final location. This process is called neuronal migration. Disruptions in genes like HNRNPC can slow or alter this migration, potentially affecting brain structure and function.

A doctor who specializes in the brain and nervous system.

A neurologist is a physician who diagnoses and treats conditions affecting the brain, spinal cord, and nerves. For children with HNRNPC-related RNDD, a neurologist may help evaluate seizures, movement differences, and other neurological symptoms.

How a condition changes over time without specific treatments.

Natural history describes the typical course of a condition from infancy through adulthood—how symptoms appear, change, and stabilize. Collecting natural history data in HNRNPC-related RNDD helps researchers understand long-term outcomes and plan future clinical trials.

Also known as: NMD

A quality-control process that destroys faulty RNA messages.

Nonsense mediated decay (NMD) is a cellular surveillance mechanism that identifies and destroys RNA messages containing errors, particularly those with premature stop signals. This prevents the cell from making incomplete or harmful proteins. Some HNRNPC variants trigger NMD, while others escape it, which may influence the severity or pattern of symptoms.

Also known as: NLS

A tag on a protein that tells it to go into the cell's nucleus.

A nuclear localization signal (NLS) is a short sequence of amino acids within a protein that acts like a postal code, directing the protein to be transported into the nucleus of the cell. The nucleus is the control center where DNA is stored and genes are regulated. If the NLS is disrupted by a mutation, the protein may not reach the nucleus and cannot perform its normal function.

Also known as: Involuntary eye movement

Involuntary, repetitive eye movements.

Nystagmus is a condition in which the eyes make repetitive, uncontrolled movements, often from side to side but sometimes up and down or in a circular pattern. These movements can affect vision, balance, and coordination. Nystagmus can be present from birth (congenital) or develop later due to various neurological or eye conditions.

Also known as: Unable to walk, Wheelchair-dependent

Unable to walk independently.

Non-ambulatory describes individuals who are unable to walk independently and may require a wheelchair, walker, or other assistive devices for mobility. This can result from various causes including muscle weakness, motor planning difficulties, balance problems, or skeletal abnormalities. Many individuals who are non-ambulatory can still achieve mobility and independence with appropriate supports and equipment.

Also known as: Bridge of the nose

The bony upper part of the nose between the eyes.

The nasal bridge is the bony part of the nose between the eyes, where glasses typically rest. Clinicians may describe it as 'broad,' 'flat,' 'depressed,' or 'prominent' when evaluating facial features. A broad nasal bridge, where the distance between the eyes at the top of the nose appears wider than typical, is noted in some genetic conditions including Au-Kline syndrome.

A research method that increases the amount of a protein made by a gene.

Overexpression occurs when a gene is engineered to produce more protein than usual. Studies of HNRNPC show that both too little and too much protein can disturb neuronal development, suggesting that proper balance is critical.

Also known as: OT

Therapy that supports daily living skills, coordination, and sensory needs.

Occupational therapists help children build fine motor skills, self-care skills (like feeding and dressing), and coping strategies for sensory challenges. OT can be very helpful for children with HNRNPC-related RNDD.

Also known as: Overriding toes

A condition where one toe overlaps another.

Overlapping toes is a condition in which one toe lies on top of or crosses over an adjacent toe. The fifth toe (pinky toe) overlapping the fourth toe is most common. This condition may be present at birth or develop over time, and can occur as part of various genetic conditions or due to structural foot differences.

Also known as: Optic nerve abnormalities, Optic nerve hypoplasia

Structural or functional differences in the optic nerve.

Optic nerve anomalies refer to various structural or functional abnormalities of the optic nerve, which transmits visual information from the eye to the brain. These can include optic nerve hypoplasia (underdevelopment), optic atrophy (damage), or other structural differences. Optic nerve anomalies can affect vision to varying degrees and may be detected through eye examination or brain imaging.

Also known as: Oral motor dysfunction, Oral motor problems

Difficulty coordinating the muscles used for eating and speaking.

Oromotor dysfunction refers to problems with the coordination of muscles in the mouth, tongue, and throat that are used for eating, drinking, and speaking. It can cause difficulties with sucking, chewing, swallowing, and speech articulation. Children with oromotor dysfunction may benefit from feeding therapy and speech therapy to improve these skills and ensure safe feeding.

A working molecule in cells that performs specific jobs.

Proteins are the main functional molecules in cells. They carry out tasks such as building structures, sending signals, and regulating other processes. Genes store the recipes for proteins, and when a gene is altered, the resulting protein can be missing, reduced in amount, or working differently, which can lead to disease.

The observable physical, developmental, or behavioral characteristics of an individual.

Phenotype refers to the traits and characteristics that can be observed or measured in a person, such as physical features, developmental milestones, medical conditions, or behavioral patterns. While genotype describes what is in someone's DNA, phenotype describes what is expressed or seen. The phenotype is influenced by both genotype and environmental factors.

Also known as: Physiotherapy, PT

Therapy that supports strength, balance, and movement.

Physical therapy focuses on gross motor skills, including crawling, walking, balance, and coordination. For children with hypotonia or motor delays related to HNRNPC, PT can improve mobility and independence.

A secure database where families can share information about a rare condition.

A patient registry gathers medical and developmental information from many individuals with the same rare condition, such as HNRNPC-related RNDD. Registries help researchers see patterns, improve care guidelines, and design clinical trials, while giving families a way to contribute to progress.

Also known as: PMG

A brain malformation with too many small folds on the brain surface.

Polymicrogyria is a condition in which the surface of the brain has an excessive number of small, irregular folds (gyri) instead of the normal pattern of folds. This occurs when brain development is disrupted, often early in pregnancy. Polymicrogyria can affect motor skills, speech, and learning, depending on which parts of the brain are involved.

Also known as: Sunken chest, Funnel chest

A chest wall shape where the breastbone is sunken inward.

Pectus excavatum is a condition in which the breastbone (sternum) and attached ribs grow inward, creating a sunken or concave appearance of the chest. It is usually present from birth or develops during childhood growth spurts. Most cases are mild and cosmetic, though severe cases can sometimes affect heart or lung function.

Also known as: Pigeon chest

A chest wall shape where the breastbone protrudes outward.

Pectus carinatum is a condition in which the breastbone (sternum) and ribs grow outward, creating a protruding or pointed appearance of the chest. It typically becomes noticeable during the adolescent growth spurt. Like pectus excavatum, it is usually a cosmetic concern rather than a functional problem.

The vertical groove between the nose and upper lip.

The philtrum is the vertical groove or indentation that runs from the base of the nose to the center of the upper lip. Variations in the philtrum's length or depth (such as a smooth or short philtrum) can be a minor finding noted in some genetic conditions. These differences are usually cosmetic and do not affect function.

Also known as: Paralog

Genes that arose from a shared ancestor and perform similar functions.

Paralogues are genes within the same organism that evolved from a common ancestral gene through duplication. They often perform similar but not identical functions. For example, HNRNPH1 and HNRNPH2 are paralogues located on different chromosomes that both help control RNA splicing in neurons. Mutations in either gene can cause related but distinct neurodevelopmental conditions.

Also known as: High arch feet, Cavus foot

An abnormally high arch of the foot.

Pes cavus is a foot condition characterized by an abnormally high arch that doesn't flatten with weight-bearing. This can cause problems with balance and walking, and may lead to foot pain, calluses, and ankle instability. Pes cavus can be present from birth or develop over time, and may occur as part of various neurological or genetic conditions.

Also known as: Pigeon chest, Keel chest

A chest wall deformity where the breastbone protrudes outward.

Pectus carinatum is a chest wall deformity in which the breastbone (sternum) and ribs push outward, creating a protruding or 'pigeon chest' appearance. It is the opposite of pectus excavatum (sunken chest). The condition is usually noticed during childhood or adolescence and may worsen during growth spurts. It can occur on its own or as part of various genetic conditions.

Also known as: Palpebral fissures, Eye opening

The opening between the upper and lower eyelids.

The palpebral fissure is the elliptical opening between the upper and lower eyelids that exposes the eye. Clinicians may measure or describe the palpebral fissures as part of evaluating facial features. Terms like 'short palpebral fissures' (smaller eye openings) or 'long palpebral fissures' (larger eye openings) may be used to describe variations that can be associated with certain genetic conditions.

Also known as: PDA

A heart condition where a blood vessel doesn't close properly after birth.

Patent ductus arteriosus (PDA) is a congenital heart defect in which the ductus arteriosus, a blood vessel that is needed before birth to bypass the lungs, fails to close after birth as it should. This allows oxygen-rich and oxygen-poor blood to mix, which can strain the heart. Small PDAs may close on their own or cause no problems, while larger ones may need medication or surgical treatment.

Also known as: HNRNP-related neurodevelopmental disorders

A group of neurodevelopmental conditions linked to HNRNP genes.

RNDD stands for HNRNP-related neurodevelopmental disorders. These are a family of rare genetic conditions caused by changes in genes that code for heterogeneous nuclear ribonucleoproteins (HNRNPs), which are important regulators of RNA. HNRNPC-related RNDD is one member of this larger group.

Also known as: Ribonucleic acid

The 'messenger' molecule that carries instructions from DNA to make proteins.

RNA is a molecule that helps transfer the genetic information stored in DNA into actual working proteins. DNA is like the master blueprint, and RNA is like a copy of one page of that blueprint that the cell uses to build a specific protein. Genes like HNRNPC help control how these RNA messages are handled.

Also known as: RBP

A protein that attaches to RNA to control how it is used.

An RNA-binding protein is a protein that physically attaches to RNA molecules and helps control how they are processed, edited, transported, or broken down. HNRNPC is one such RNA-binding protein and plays a key role in how RNA is shaped into final instructions for making other proteins.

Also known as: RNA-seq

A laboratory method for measuring which genes are turned on and how.

RNA sequencing is a research technique used to read and count RNA molecules in a cell. It helps scientists see which genes are active and how splicing patterns change. In HNRNPC-related research, RNA-seq helps identify which other genes are affected when HNRNPC levels are low.

A test to see if restoring a gene's function can improve symptoms in models.

In a rescue experiment, researchers try to correct or compensate for a genetic defect in a model system (like cells or mice) to see if the abnormal features improve. This helps confirm that the gene truly causes the observed problems and can point toward future treatment strategies.

Damage or disease affecting the retina at the back of the eye.

Retinopathy refers to any disease or damage to the retina, the light-sensitive tissue at the back of the eye that sends visual signals to the brain. Various conditions can cause retinopathy, affecting vision to different degrees depending on the type and severity.

Also known as: Rett's syndrome

A rare genetic neurological disorder affecting brain development, primarily in females.

Rett syndrome is a rare genetic disorder that affects brain development, causing progressive loss of motor skills and speech after initial normal development. It primarily affects females and is usually caused by mutations in the MECP2 gene. Symptoms typically appear between 6-18 months of age and may include repetitive hand movements, breathing problems, and seizures. Some individuals with HNRNPH2-RNDD present with features similar to Rett syndrome.

Also known as: Hyporeflexia, Diminished reflexes

Weaker than normal reflexes when tested.

Reduced reflexes, also called hyporeflexia, refers to diminished or absent reflex responses when tested by a doctor (such as the knee-jerk reflex). This can indicate problems with the nerves, muscles, or the connections between them. Reduced reflexes are noted in some individuals with neurodevelopmental conditions and may be associated with hypotonia (low muscle tone).

Also known as: Drug-resistant epilepsy, Intractable seizures

Seizures that do not respond well to standard medications.

Refractory seizures, also called drug-resistant or intractable seizures, are seizures that continue despite treatment with appropriate anti-seizure medications. Generally, seizures are considered refractory when two or more medications have been tried at adequate doses without achieving seizure control. Alternative treatments such as the ketogenic diet, newer medications, or sometimes surgery may be considered.

Also known as: RNA splicing

The process where extra pieces are cut out of RNA before it makes a protein.

Splicing is a normal cellular process in which non-coding sections (introns) are removed from RNA and coding sections (exons) are joined together. This editing step is essential so that the RNA can provide accurate instructions to make a working protein. HNRNPC helps guide which pieces are kept or removed.

Also known as: Language delay

Slower development of spoken language compared with peers.

Speech delay means that a child is later than expected in using words, phrases, or sentences. Children with HNRNPC-related RNDD often experience delayed speech and may benefit from early and ongoing speech therapy.

A temporary burst of abnormal electrical activity in the brain.

A seizure is a sudden, brief episode that can cause changes in awareness, movement, or behavior due to abnormal electrical activity in the brain. Some individuals with HNRNPC-related RNDD experience seizures and may be diagnosed with epilepsy.

Problems with falling asleep, staying asleep, or having restful sleep.

Sleep difficulties can be common in children with neurodevelopmental conditions. These may include frequent awakenings, difficulty falling asleep, or early morning waking. Good sleep hygiene and, when needed, medical guidance can help improve sleep patterns.

The connection point where two neurons communicate.

A synapse is a small gap where one neuron sends signals to another using chemical messengers. Healthy synapse formation and function are crucial for learning and memory. Genes involved in RNA processing, like HNRNPC, can indirectly influence synapse development through their effects on many other genes.

Also known as: Speech and language therapy

Therapy that supports communication, understanding, and speaking.

Speech therapy helps children develop skills in understanding language, producing speech, and using communication tools if needed. Many children with HNRNPC-related RNDD benefit from early and ongoing speech therapy.

Also known as: Brain malformations, Brain abnormalities

Differences in the structure or shape of the brain visible on imaging.

Structural brain anomalies are differences in the physical structure of the brain that can be seen on imaging studies like MRI. These may include changes in the size of certain brain regions, abnormalities in how brain tissue is organized, or differences in fluid-filled spaces. Many individuals with HNRNPC-related RNDD have some form of structural brain anomaly, though these can vary widely in type and severity.

Also known as: Sandal gap deformity, Wide first toe space

An unusually wide space between the big toe and second toe.

A sandal gap refers to an increased space between the first toe (big toe) and the second toe, resembling the space created by a sandal strap. This is a minor physical finding that can be present at birth and is observed in various genetic conditions. It does not typically cause functional problems.

Also known as: Skeletal differences, Bone abnormalities

Differences in the bones or skeletal system.

Skeletal anomalies refer to a wide range of differences in the development or structure of bones. These can include differences in bone size, shape, or number, and may affect the spine, skull, limbs, or other parts of the skeleton. In HNRNPC-related RNDD, skeletal differences are observed in about one-third of individuals.

Also known as: Crossed eyes, Squint, Eye misalignment

A condition where the eyes do not align properly.

Strabismus is a condition in which the eyes do not look in the same direction at the same time. One eye may turn inward, outward, upward, or downward while the other eye looks straight ahead. Strabismus can be constant or intermittent and may affect depth perception. Treatment options include glasses, eye exercises, or surgery, depending on the type and cause.

Also known as: Curvature of the spine

An abnormal sideways curve of the spine.

Scoliosis is a condition in which the spine curves sideways in an S or C shape instead of running straight. It can range from mild to severe. Mild scoliosis may not require treatment, while more significant curves may need bracing or surgery. Scoliosis can occur on its own or as part of genetic conditions.

Also known as: Webbed fingers, Webbed toes, Fused digits

A condition where two or more fingers or toes are joined together.

Syndactyly is a congenital condition in which two or more fingers or toes are fused or webbed together. It can range from a thin skin connection to complete fusion including bones. Syndactyly is one of the most common congenital hand and foot differences and can occur on its own or as part of various genetic syndromes. Treatment may involve surgical separation depending on the severity and functional impact.

Also known as: Spastic muscles, Muscle stiffness

Abnormal muscle tightness due to prolonged muscle contraction.

Spasticity is a condition in which muscles are continuously contracted, causing stiffness or tightness that can interfere with movement and speech. It is caused by damage to the nerve pathways within the brain or spinal cord that control muscle movement. Spasticity may affect any muscle group and can range from mild to severe. Treatment options include physical therapy, medications, and sometimes surgery.

Also known as: SIB, Self-harm behavior

Behaviors that cause physical harm to oneself.

Self-injurious behavior (SIB) refers to actions that cause physical harm to one's own body, such as head banging, biting, scratching, or hitting oneself. In individuals with neurodevelopmental conditions, these behaviors may occur as a form of communication, sensory stimulation, or response to frustration. Understanding the underlying causes and implementing appropriate behavioral and environmental interventions can help reduce these behaviors.

Also known as: Stereotypical movements, Stereotyped movements, Repetitive movements

Repetitive, purposeless movements or behaviors.

Stereotypies are repetitive, seemingly purposeless movements, postures, or vocalizations such as hand flapping, body rocking, head nodding, or finger movements. They are common in individuals with autism spectrum disorder and other neurodevelopmental conditions. While often harmless, stereotypies may sometimes interfere with daily activities or social interactions.

Also known as: Small stature, Growth delay

Height significantly below average for age and sex.

Short stature refers to height that is significantly below the typical range for a person's age and sex, usually defined as below the 3rd percentile on growth charts. It can have many causes including genetic conditions, hormone deficiencies, chronic illness, or nutritional factors. Evaluation by an endocrinologist can help determine the cause and whether treatment options like growth hormone therapy may be appropriate.

Also known as: Valproate, Valproic acid, Depakote, Epilim

A commonly used anti-seizure medication.

Sodium valproate is a medication widely used to treat epilepsy and control various types of seizures. It works by stabilizing electrical activity in the brain. In HNRNPU-related neurodevelopmental disorder, sodium valproate is often used as a first-line treatment and is frequently effective. However, it requires monitoring of liver function and may not be appropriate for women of childbearing age due to risks to developing babies.

Also known as: Obstructive sleep apnea, OSA

A sleep disorder where breathing repeatedly stops and starts.

Sleep apnea is a potentially serious sleep disorder in which breathing repeatedly stops and starts during sleep. The most common type, obstructive sleep apnea, occurs when throat muscles relax and block the airway. Symptoms include loud snoring, episodes of stopped breathing observed by another person, gasping for air during sleep, and daytime tiredness. Sleep apnea can be evaluated with a sleep study and treated with various interventions including CPAP, positional therapy, or surgery.

Also known as: HNRNPQ, Synaptotagmin-binding cytoplasmic RNA-interacting protein

A gene that helps control RNA processing, especially in the brain.

SYNCRIP (also known as HNRNPQ) is a gene that provides instructions for making a protein involved in RNA processing and regulation. It is part of the HNRNP gene family and plays an important role in brain development, helping neurons form connections and communicate. Changes in SYNCRIP can cause SYNCRIP-related neurodevelopmental disorder.

Also known as: SYNCRIP-RNDD, HNRNPQ-RNDD, HNRNPQ-related disorder

A genetic condition caused by changes in the SYNCRIP gene affecting brain development.

SYNCRIP-related neurodevelopmental disorder is a genetic condition caused by changes in the SYNCRIP gene. It can cause a range of developmental and neurological differences that vary widely from person to person—some children are mildly affected while others experience more significant challenges. Common features include developmental delay, speech difficulties, autism spectrum disorder or autistic traits, and low muscle tone. Most cases occur spontaneously (de novo).

Also known as: Sensory processing differences, Sensory integration

How the brain receives and responds to information from the senses.

Sensory processing refers to how the nervous system receives, organizes, and responds to sensory information from the environment (sight, sound, touch, taste, smell, movement, and body awareness). Some children have sensory processing differences, meaning they may be over-sensitive or under-sensitive to certain sensory inputs, or may seek out certain sensory experiences. Occupational therapy can help children with sensory processing challenges.

Genetic testing done on a child and both parents together.

Trio sequencing involves testing the child and both biological parents at the same time. This approach helps determine whether a genetic variant is inherited or de novo and can speed up diagnosis for conditions like HNRNPC-related RNDD.

Also known as: Thalamic

A deep brain structure that relays sensory information.

The thalamus is a structure deep in the center of the brain that acts as a relay station for sensory and motor signals. It helps process information from the senses and coordinates movement. Thalamic abnormalities refer to structural or functional differences in this region that can be identified on brain imaging.

Also known as: Grand mal seizures, Generalized tonic-clonic seizures

Seizures involving muscle stiffening followed by rhythmic jerking.

Tonic-clonic seizures, previously called grand mal seizures, are a type of generalized seizure that involves two phases: the tonic phase (when muscles stiffen) and the clonic phase (when muscles rhythmically contract and relax, causing jerking movements). These seizures typically cause loss of consciousness and may be followed by confusion or fatigue. They can be associated with various types of epilepsy and genetic conditions.

Also known as: Tremors, Shaking

Involuntary, rhythmic shaking of a body part.

A tremor is an involuntary, rhythmic muscle contraction leading to shaking movements in one or more parts of the body. Tremors most commonly affect the hands but can also involve the arms, head, face, voice, trunk, or legs. They can occur at rest or during movement and may be caused by neurological conditions, medications, or other factors.

Also known as: Tapering fingers, Long tapered fingers

Fingers that become progressively narrower toward the tips.

Tapered fingers describe a finger shape where the digits gradually become narrower from the base toward the fingertips, giving an elongated, slender appearance. This can be a normal variation or may be associated with various genetic conditions. Tapered fingers are sometimes noted along with other hand differences during clinical evaluation.

Also known as: VUS

A genetic change where it's not yet clear if it causes disease.

A variant of uncertain significance is a DNA change that has been found, but there is not enough scientific evidence to say whether it is harmless or disease-causing. As more families and data are collected, some VUS in HNRNPC may be reclassified.

Also known as: Brain ventricles, Cerebral ventricles

Fluid-filled spaces inside the brain.

The ventricles are a system of connected, fluid-filled cavities within the brain. They produce and contain cerebrospinal fluid (CSF), which cushions and protects the brain. The size and shape of ventricles can vary, and abnormally large ventricles (ventriculomegaly) may be seen in some genetic conditions.

Also known as: Enlarged ventricles, Large ventricles

Abnormally enlarged fluid-filled spaces in the brain.

Ventriculomegaly refers to enlargement of the brain's ventricles, the fluid-filled cavities that hold cerebrospinal fluid. This finding can be seen on brain MRI or prenatal ultrasound. While mild ventriculomegaly may have no symptoms, more significant enlargement can be associated with developmental differences. It is one of the structural brain anomalies observed in some individuals with HNRNPC-related RNDD.

Also known as: Vertebra, Spinal bones

The individual bones that make up the spine.

Vertebrae are the small bones stacked on top of each other to form the spinal column (backbone). They protect the spinal cord and provide structure for the body. Vertebral anomalies may include differences in the shape, number, or fusion of these bones.

Also known as: Vertebral anomalies, Spinal segmentation defects

Abnormalities in how the bones of the spine are formed.

Vertebral segmentation anomalies are differences in how the vertebrae (bones of the spine) form during fetal development. This can include vertebrae that are fused together, partially formed, or abnormally shaped. These differences may be seen on X-ray or other imaging and can range from having no symptoms to causing scoliosis or other spinal problems. Regular monitoring may be recommended.

Also known as: VSD, Hole in the heart

A hole in the wall between the two lower chambers of the heart.

A ventricular septal defect (VSD) is a congenital heart defect in which there is a hole in the septum (wall) that separates the two lower chambers (ventricles) of the heart. This allows oxygen-rich blood from the left ventricle to mix with oxygen-poor blood in the right ventricle. Small VSDs may close on their own and cause few problems, while larger ones may require surgical repair.

Also known as: WES

A test that reads the protein-coding parts of nearly all genes.

Whole exome sequencing is a genetic test that examines the exons (protein-coding regions) of thousands of genes at once. It is commonly used to identify rare genetic variants that cause neurodevelopmental disorders, including HNRNPC-related RNDD.

Also known as: Infantile spasms

A type of severe epilepsy in infants with characteristic spasms and EEG pattern.

West syndrome is a severe form of epilepsy that typically begins in the first year of life. It is characterized by infantile spasms (sudden, brief stiffening movements, often occurring in clusters), a specific abnormal EEG pattern called hypsarrhythmia, and developmental regression or delay. West syndrome can have many underlying causes, including genetic conditions, and requires prompt treatment to try to preserve development.

Also known as: Cerebral white matter

The tissue in the brain that contains nerve fibers connecting different brain regions.

White matter is the tissue in the brain made up of nerve fibers (axons) covered in myelin, which gives it a whitish appearance. These fibers connect different regions of the brain and allow them to communicate with each other. White matter abnormalities on brain imaging can indicate problems with these connections and may be associated with developmental or neurological conditions.

Also known as: X-linked, X-linked disorder

A pattern of inheritance where the gene is located on the X chromosome.

X-linked inheritance is a pattern of genetic inheritance in which the gene responsible for a condition is located on the X chromosome. Because females have two X chromosomes (XX) and males have one X and one Y chromosome (XY), X-linked conditions often affect males more severely than females. Females may be carriers or have milder symptoms because they have a second X chromosome that may compensate. X-linked conditions can be dominant or recessive.