OMIM ID:
Knobloch Syndrome 2
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
In an 18 month infant, ectopia lentis, cataract, and myopia with poor vision were noted. This individual subsequently developed retinal degeneration and a serous retinal detachment.
Systemic Features
Only one patient has been reported. While the clinical signs resemble Knobloch 1 syndrome, brain imaging does not reveal malformations in this syndrome. The only systemic sign, in addition to an occipital encephalocele, is a minor delay in fine motor skills.
Genetics
Inheritance
This autosomal recessive disorder results from homozygous loss of function mutations in the ADAMTS18 gene (16q23.1). The gene product has been found in the lens and retina in the murine eye.
Mutations in ADAMTS18 have also been found in the syndrome of Micorcornea, Myopia, Chorioretinal atrophy, and Telecanthus. It may also be responsible for a retinal dystrophy.
Knobloch 2 syndrome was identified in a single female born to consanguineous parents.
This disorder is separate to Knobloch 1 syndrome (267750) based on the causative mutations. A third type, KNO3, has been proposed since the Knobloch clinical features were found in a 4-generation consanguineous Pakistani family but the phenotype mapped to 17q11.2.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.