Knobloch Syndrome 2

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 [1], 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

This autosomal recessive disorder results from homozygous loss of function mutations in the ADAMTS18 [2] gene (16q23.1). The gene product has been found in the lens and retina in the murine eye.

Mutations in ADAMTS18 [3] have also been found in the syndrome of Micorcornea, Myopia, Chorioretinal atrophy, and Telecanthus [4]. 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 [1] (267750 [5]) 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.

Treatment

Treatment Options:

The skull defect can be closed and the lenses can be removed if indicated.

References

Article Title:

The ADAMTS18 gene is responsible for autosomal recessive early onset severe retinal dystrophy [6]

Peluso I, Conte I, Testa F, Dharmalingam G, Pizzo M, Collin RW, Meola N, Barbato S, Mutarelli M, Ziviello C, Barbarulo AM, Nigro V, Melone MA; European Retinal Disease Consortium, Simonelli F, Banfi S. The ADAMTS18 gene is responsible for autosomal recessive early onset severe retinal dystrophy. Orphanet J Rare Dis. 2013 Jan 28;8:16.

PubMed ID:

23356291

Identification of ADAMTS18 as a gene mutated in Knobloch syndrome [7]

Aldahmesh MA, Khan AO, Mohamed JY, Alkuraya H, Ahmed H, Bobis S, Al-Mesfer S, Alkuraya FS. Identification of ADAMTS18 as a gene mutated in Knobloch syndrome. J Med Genet. 2011 Sep;48(9):597-601.

PubMed ID:

21862674

Mapping of a novel type III variant of Knobloch syndrome (KNO3) to chromosome 17q11.2 [8]

Khaliq S, Abid A, White DR, Johnson CA, Ismail M, Khan A, Ayub Q, Sultana S, Maher ER, Mehdi SQ. Mapping of a novel type III variant of Knobloch syndrome (KNO3) to chromosome 17q11.2. Am J Med Genet A. 2007 Dec 1;143A(23):2768-74.

PubMed ID:

17975799