SYNCRIP/HNRNPQ-Related Neurodevelopmental Disorder
The SYNCRIP gene is also called HNRNPQ. This is because the gene was identified by multiple groups who called it different things. The official gene name is SYNCRIP.
SYNCRIP/HNRNPQ-Related Neurodevelopmental Disorder is caused by damaging genetic changes (variants) in the SYNCRIP gene.
Genetics
SYNCRIP/HNRNPQ-Related Neurodevelopmental Disorder follows an autosomal dominant inheritance pattern.
Most variants are loss-of-function and result in a nonfunctional protein product that leads to a decreased amount than necessary the of SYNCRIP/hnRNPQ protein that is needed for normal cellular function (haploinsufficiency).
Missense and insertion/deletion (indel) variants are rarer but have been reported more frequently with increased genomic testing. The mechanism of such variants is still unclear, but may include loss-of-function or gain-of-function. No significant differences have been observed across variant types.
To date, all variants reported in the medical literature are de novo, which means that they occurred for the first time in the affected person and were not inherited from a parent. However, we are aware of inherited variants that have yet to be published. These seem to be inherited from an affected parent, but their child may have differing/more severe clinical features.
Developmental Delay/Intellectual Disability
All HNRNPC-RNDD individuals have developmental delay/intellectual disability to date. This ranges from mild to moderate.
Motor
Most individuals with HNRNPC-RNDD have motor delay. One individual who has a large exon 1-3 deletion did not have gross motor delay, but other individuals had delayed walking, with first steps being up to 2.5 years old. All individuals have delays in fine motor skills.
Structural Brain Anomalies
Most individuals with HNRNPC-RNDD have structural brain anomalies. These are quite variable. The following have been reported:
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Abnormal ventricles, particulary large ventricles (ventriculomegaly)
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Absent cochlea (leading to hearing loss)
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Polymicrogyria
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Delayed myelination
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Cysts
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Thalamic volume loss
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Small sinuses
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Muscles
Over half of individuals with HNRNPC-RNDD have hypotonia (low muscle tone).
A small number of individuals with variants that escape nonsense mediated decay have hypermobile joints.
Hand and Feet Differences
About 60% of individuals with HNRNPC-RNDD have hand and/or feet differences. Reported differences include:
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fetal fingertip pads or prominent fingertip pads
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small metacarpals (bones of the hand)
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sandal gap between toes
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metatarsus adductus (front of the foot turns inward)
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clinodactyly (curved finger)
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brachydactyly (short fingers)
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short or small hands or feet
Hearing Loss
Almost half of individuals with HNRNPC-RNDD have eye and/or vision anomalies. These include:
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myopia (near-sightedness)
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colobomatous microphthalmia
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strabismus
Speech
All HNRNPC-RNDD individuals have speech delay or problems. Some individuals are nonverbal while some are delayed until 2-3 years old. Multiple people have articulation issues.
Behavioral Differences
Most individuals with HNRNPC-RNDD have behavioral differences. These include a happy demeanor, ADHD, autism spectrum disorder (ASD), and difficulty falling or staying asleep. Tics have also been reported.
Seizures
About a quarter of individuals with HNRNPC-RNDD have seizures. These have included:
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absence seizures
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generalized seizures
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epilepsy
Individuals with variants that escape nonsense mediated decay are more likely to have seizures.
Skeletal Differences
About a third of individuals with HNRNPC-RNDD have skeletal differences. Individuals with variants that escape nonsense mediated decay are more likely to have skeletal differences. Reported differences include:
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vertebrae anomalies
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thin ribs
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abnormal number of ribs
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pectus excavatum-carinatum
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tiba anomalies
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open anterior fontanelle
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short neck
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brachycephaly
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microcephaly
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macrocephaly
Eye and Vision Anomalies
Almost half of individuals with HNRNPC-RNDD have eye and/or vision anomalies. These include:
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myopia (near-sightedness)
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colobomatous microphthalmia
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strabismus
SYNCRIP/HNRNPQ Research
Here are the most up to date research papers on SYNCRIP/HNRNPQ-Related Neurodevelopmental Disorder
In this publication, Dr. Maddie Gillentine lead our team to further define the features of SYNCRIP/HNRNPQ-Related Neurodevelopmental Disorder.
You can read the article here:
