OMIM ID:
Cataracts, Hearing Loss, and Neurodegeneration
Defective Genes
Clinical Characteristics
Ocular Features
Congenital cataracts are the important ocular feature in this syndrome.
Systemic Features
Hearing loss is an important part of this syndrome. Severe hypomyelination and hypoplasia are seen on MRI. Marked developmental delay and early death are also seen. Reduced ceruloplasmin secretion and low serum copper are present.
Genetics
Inheritance
This is an autosomal recessive disorder resulting from homozygous or compound heterozygous mutations in SLC33A1 (3q25) encoding an acetylCoA transporter (AT-1). The defect in hepatic cells results in reduced ceruloplasmin secretion with low serum copper. Wilson disease (277900), Menkes disease (309400), and aceruloplasminemia (604290), other disorders of copper metabolism, have similar blood findings but due to different mechanisms.
Heterozygous mutations in SLC33A1 result in an autosomal dominant form of spastic paraplegia (SPG42) (612539). No ocular abnormalities have been reported in SPG42 though.
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.