OMIM ID:
Congenital Disorder of Glycosylation, Type Iq
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Colobomas (iris, choroid, and sometimes optic nerve), optic nerve hypoplasia and nystagmus have been reported. Visual acuity is variable depending upon the degree of nerve hypoplasia. The eyebrows may be highly arched, while downward slanting lid fissures, and hypertelorism may also be present.
Congenital cataracts, glaucoma and microphthalmia have been reported in several individuals.
Systemic Features
Onset of symptoms commonly begins in infancy with severe hypotonia while developmental delays soon become evident as most children do not achieve normal milestones. The amount of cognitive impairment is variable. Congenital cardiac defects, ichthyosis, and hypertrichosis may be present. The skin over the dorsum of the hands and feet often appears dark. Ataxia is sometimes present and MRIs may reveal vermal and cerebellar hypoplasia.
Facial dysmorphism is common. Low-set malformed ears, low hairline, depressed nasal bridge, redundant facial skin, decreased subcutaneous tissue, large mouth, thin lips, and long face have been noted.
There is considerable variation in clinical manifestations and longevity varies from infancy to adulthood.
Genetics
Inheritance
This glycosylation disorder is one of a number of rare hepatic/intestinal disorders caused by a deficiency in N-oligosaccharide synthesis. It is inherited in an autosomal recessive pattern as a result of mutations in SRD5A3 (4q12). Both homozygous and compound heterozygous genotypes have been reported. It is allelic to Kahrizi syndrome (612713) with a number of overlapping features including ocular colobomas and cognitive deficiencies.
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.