SYNCRIP/HNRNPQ-Related Neurodevelopmental Disorder
SYNCRIP-related neurodevelopmental disorder (also called HNRNPQ-RNDD) is a rare genetic condition caused by changes in the SYNCRIP gene, which plays an important role in how the brain develops and communicates. As part of the HNRNP gene family, SYNCRIP helps control how RNA is processed inside cells—a key step in making proteins that support learning, movement, and brain growth. The condition can vary widely from person to person, with some children mildly affected while others experience more significant challenges.
The Gene
SYNCRIP (also known as HNRNPQ) is a gene that helps control how RNA is processed inside cells. It's part of the larger HNRNP family of genes that regulate the messages cells use to build proteins. SYNCRIP is particularly important in the brain, where it helps neurons develop, communicate, and form the connections needed for learning and movement.
Why It Matters for the Brain
When one copy of SYNCRIP doesn't work properly, cells may not process RNA correctly. This can affect how the brain develops and functions. The good news is that most children with SYNCRIP-RNDD have mild to moderate challenges, and many make significant progress with the right therapies and support.
Most variants are de novo, meaning neither parent carries the variant—it occurs as a new, spontaneous change. This means the chance of it happening again in the same family is generally very low. Diagnosis requires genetic testing, usually through whole exome sequencing, genome sequencing, or multigene neurodevelopmental panels.
Variant types observed:
- Loss-of-function variants
- Missense variants
- Frameshift variants
- Splice site variants
Brain development
SYNCRIP is particularly important in the developing brain, where it helps neurons form connections and communicate with each other. Reduced function can affect learning, movement, and behavior.
Learning & Development
~90%Most children have developmental delay/intellectual disability ranging from borderline to moderate. Fine and gross motor delays are common, such as later walking and coordination difficulties. Speech delays are common and may be complicated by speech apraxia. Children continue to learn and develop throughout childhood with appropriate support.
Speech & Communication
~85%Speech delay is very common. Some children speak in short sentences, while others use only a few words or rely on alternative communication (AAC). Speech therapy, including AAC devices, can make a significant difference.
Behavior & Social Differences
~80%Many children have autism spectrum disorder or autistic characteristics. Attention difficulties and ADHD are frequently seen. Some children exhibit sensory differences, anxiety, or behavioral rigidity. Sleep disturbances or challenges have also been reported.
Muscle Tone & Movement
~40%Hypotonia (low muscle tone) is common, especially in infancy. Some children develop mild balance or gait differences. Joint hypermobility may also be present. Physical and occupational therapy help improve strength and coordination.
Seizures
~30%Some children experience seizures, including absence seizures or febrile seizures. Others may have abnormal EEG findings without obvious clinical seizures. Often, children with SYNCRIP-RNDD are diagnosed with seizures or epilepsy in early to mid childhood. Neurological evaluation is recommended.
Brain Differences
MRI findings, when present, may include structural brain differences, Chiari malformation, ventricular enlargement, or abnormalities in white matter or corpus callosum. Not all children have MRI findings.
Physical Features
Physical features are subtle and vary between children. Because these features are mild and inconsistent, they do not define the condition.
- Mildly deep-set eyes
- Abnormal palpebral fissures
- Polymicrogyria
- Prominent or protruding ears
- Thin or full lips
- Full cheeks
- Subtle hand/feet differences such as sandal gap
Eyes & Vision
~40%Eye and vision differences have been observed among individuals with SYNCRIP-RNDD.
- Strabismus
- Near sightedness or far sightedness
- Astigmatism
- Nystagmus
- Optic nerve anomalies
Kidney & Urinary System
~30%Kidney anomalies have been observed.
- Chronic kidney disease
- Neurogenic bladder
Growth
Children may have typical growth, short stature, or overgrowth/higher weight percentiles. Patterns vary widely even within the same family.
Other Possible Features
Not every child will experience these, but they have been reported in some cases.
- Feeding challenges in infancy
- Sleep disturbances
- Gastrointestinal concerns
- Hearing or vision issues
- Rare breathing differences
- Kidney or cardiac findings (rare)
Receiving a SYNCRIP-RNDD diagnosis can feel overwhelming, but you are not alone. While this is a rare condition, families and researchers are actively working together to understand it better. Every child is unique—the features described here represent what has been observed so far, and your child may experience a different combination. Most of the time, this condition occurs spontaneously (de novo), meaning parents did not pass the variant down and could not have predicted it.
- Speech delay is very common, but children often benefit greatly from speech therapy and communication devices (AAC).
- Many children have autism spectrum disorder or autistic characteristics, and autism-focused therapies can be very helpful.
- Hypotonia (low muscle tone) is common in infancy but often improves with physical therapy.
- Some children experience seizures, but not all—neurological monitoring is recommended.
- Early intervention and personalized care plans make a meaningful difference.
- Connect with other families through the HNRNP Family Foundation community.
Dr. Madelyn Gillentine
Rare Disease Geneticist & Clinical Genomics Scientist
HNRNP Family Foundation
Dr. Gillentine serves as Research Director at the HNRNP Family Foundation, where she leads efforts to understand SYNCRIP-related neurodevelopmental disorder and other HNRNP conditions. Her research focuses on expanding the clinical phenotype and advancing our understanding of these rare genetic conditions.
Join Our Research
We are running a Natural History Study for SYNCRIP-RNDD at the HNRNP Family Foundation. Your participation helps advance research and treatment development.
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