Polymicrogyria and Schizencephaly

Gene: COL18A1

Green List (high evidence)

Knobloch syndrome is a rare, autosomal recessive, developmental disorder characterized by stereotyped ocular abnormalities with or without occipital skull deformities (encephalocele, bone defects, cutis aplasia). Several patients have been found to have brain malformations, although these are relatively rare and not traditionally considered a hallmark feature of Knobloch syndrome.

In additional to more typical features of Knobloch syndrome, the following patients had these brain malformations:

PMID: 25456301 – 3 unrelated patients with polymicrogyria, 1 unrelated patient with cerebellar vermian atrophy. All with homozygous frameshift variants in COL18A1 (consanguineous parents in each case)

PMID: 19160445 – 2 affected siblings with polymicrogyria, both with homozygous frameshift variant in COL18A1

PMID: 17546652 – 1 patient with pachygyria/polymicrogyria and heterotopic hypersignals, with a homozygous splicing variant in COL18A1

At least 5 unrelated families have been described with biallelic loss of function variants in COL18A1 and malformations of cortical development in addition to typical features of Knobloch syndrome. Recommended for green status.

Created: 28 Apr 2020, 1:39 a.m. | Last Modified: 28 Apr 2020, 1:39 a.m.

Panel Version: 0.45

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Knobloch syndrome, type 1 MIM# 267750

Publications

• PMID: 25456301
• 19160445
• 17546652