Knobloch Syndrome in Siblings with Posterior Fossa Malformations Along with Cerebellar Midline Cleft Abnormality Caused by Biallelic COL18A1 Mutation: Case-Based Review
| Autor: | Shruti Pande, Minal Kekatpure, Venkatraman Bhat, Jyoti Matalia, Katta M. Girisha, Siddaramappa J. Patil |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
Pathology medicine.medical_specialty Occipital encephalocele Ataxia business.industry Retinal detachment Knobloch syndrome medicine.disease 03 medical and health sciences Epilepsy 0302 clinical medicine Pediatrics Perinatology and Child Health 030221 ophthalmology & optometry Polymicrogyria medicine medicine.symptom Abnormality business Genetics (clinical) Exome sequencing 030304 developmental biology |
| Zdroj: | J Pediatr Genet |
| Popis: | Knobloch syndrome (KS) is an autosomal recessive disorder caused by biallelic pathogenic variants in COL18A1. KS clinically manifests with the typical eye findings (high myopia, vitreoretinal degeneration, retinal detachment, and lens subluxation), variable neurological findings (occipital encephalocele, polymicrogyria, cerebellar malformations, epilepsy, and intellectual disability), and the other uncommon clinical manifestations. Literature review of all KS patients (source PubMed) was done with special reference to cerebellar abnormalities. Here, we report two siblings with typical KS with posterior fossa malformations and novel cerebellar midline cleft abnormality analyzed by whole exome sequencing. Known pathogenic homozygous variant c.2908C > T; (p.Arg970Ter) in exon 26 of COL18A1 was found as a cause for KS. These two siblings presented with early-onset severe ocular manifestations, facial dysmorphism, and variable central nervous system manifestations along with novel cerebellar midline cleft abnormality. The presence or absence of structural brain malformations and genotypes does not absolutely predict cognitive functions in KS patients. However, the presence of posterior fossa abnormality may be predictive for the development of ataxia in later life and needs further studies. |
| Databáze: | OpenAIRE |
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