OMIM ID:
Encephalopathy, Early-Onset, With Brain Atrophy and Thin Corpus Callosum
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Optic atrophy is present in many patients and may be present early since lack of visual tracking or eye contact may be noted at birth. Sparse eyebrows, upslanting palpebral fissures, and hypertelorism have also been reported.
Systemic Features
Severe hypotonia is present at birth often causing respiratory distress in the neonate. Spasticity can develop later. Growth failure with progressive microcephaly is present in infants. Brain imaging often reveals diffuse atrophy of structures including the cerebellum, brainstem, spinal cord, and cerebrum. Tongue fasciculations have been observed. Micrognathia and widely spaced teeth are sometimes present. Several patients have died during infancy.
Genetics
Inheritance
Homozygous mutations in the TBCD (17q25.3) are responsible for this disorder.
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.