Knobloch Syndrome 3
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
High myopia and marked nystagmus are cardinal ocular findings. Night blindness leads to symptoms between 2 and 4 years of age. Vision loss leads to complete blindness by age 15 to 18. Visual acuity in young adults is often 20/400 to NLP. Cataracts with subluxated lenses, glaucoma, and chorioretinal atrophy are often present. Scattered pigment clumping, attenuation of the retinal vasculature, and prominent choroidal vessels can often be seen. Marked optic atrophy is usually present. Phthisis and band keratopathy may be seen in older individuals although no retinal detachments have been reported. The vitreous is described as degenerated in several patients and a vitreal hemorrhage was seen in one patient.
Systemic Features
This variant was identified in a four-generation consanguineous Pakistani family in which detailed information was obtained in 5 members. A hairless, purplish-red patch is usually present in the occipital-parietal region during infancy but becomes smaller as children grow. No encephalocele is present. Hearing loss and heart defects have not been reported. Intelligence is normal.
Genetics
Inheritance
This is an autosomal recessive condition resulting from a presumed homozygous mutation on chromosome 17 (17q11.2).
Other variants of Knobloch syndrome are Knobloch 1 (267750) caused by homozygous mutations in COL18A1 (21q22.3) and Knobloch 2 (608454) secondary to homozygous mutations in ADAMTS18 at 16q23.1.
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.