OMIM ID:
Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 3
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Deep-set eyes with highly arched eyebrows have been described and poor fixation can be present. Cortical visual impairment has been described.
Systemic Features
The neurologic abnormalities become evident soon after birth. Hypotonia and decreased reflexes may be present early and often there is little psychomotor development subsequently. Some patients have no or very little speech and may never sit, stand, or walk. However, there is considerable variation in the clinical picture and other individuals are able to walk and may live into the third decade. Brain imaging reveals a variety of abnormalities including cerebellar and cerebral hypoplasia. Respiratory difficulties and poor feeding are often present.
The facial dysmorphism may include brachycephaly with a broad forehead and narrowing of the temporal regions. The nose may be small and the mouth appears large in the presence of micrognathia and a thin upper lip.
Genetics
Inheritance
This is an autosomal recessive condition as the result of homozygous or compound heterozygous mutations in the TBCK gene (4q24).
Other similar conditions include IHPRF2 (616801) (with homozygous mutations in UNC80 and IHPRF1 (615419) (with homozygous mutations in NALCN) whose ocular features may include strabismus, nystagmus, and poor visual fixation.
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.