Polymicrogyria in cases of pathogenic variants in COL18A1 gene, associated with Knobloch syndrome type 1
Keywords:
Knobloch syndrome, COL18A1, PolymicrogyriaAbstract
Knobloch syndrome is a rare and clinically heterogeneous autosomal recessive disease caused by mutations in the COL18A1 gene, that is located on the long arm of chromosome 21 (chr 21q22.3). The gene encodes collagen XVIII, which is an important component of basement membranes. Pathogenic variants of COL18A1 are found in homozygotes and compound heterozygotes.
Knobloch syndrome is characterized by typical ocular abnormalities and cranial dysraphism. Besides these features, central nervous system involvement is rare, although there are increasing reports of concomitant migration disorders, delayed psycho-motor development and epilepsy.
We present a case of a 2 years and 4 months old boy with speech delay, ataxia, large amplitude horizontal nystagmus and occipital dermal sinus. MRI of the brain shows bilateral polymicrogyria, enlarged cysterna magna, spinocerebellar hypoplasia and occipital dermal sinus. Exome sequencing identified two likely pathogenic variants in the COL18A1 gene in a heterozygous state, suggesting that the boy is a compound heterozygote.
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