OMIM ID:
Encephalopathy, Progressive, Early-Onset, wtih Brain Atrophy and Spasticity
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Optic atrophy or cortical visual impairment with lack of visual tracking have been described in all patients.
Systemic Features
Microcephaly is evident at birth with global developmental delay and hearing loss. One patient of 3 reported in 2 unrelated families had brief flexion seizures at 5 months. Developmental regression and stagnation may become evident within the first months of life. The EEG showed a hypsarrhythmia pattern. Truncal hypotonia, spasticity, dystonia and/or myoclonus, scoliosis, and dysphagia are also features. Two of the three reported patients had seizures.
Brain MRI showed a pattern of pontine hypoplasia, partial agenesis of the corpus callosum, modified frontal gyri and diffuse cortical atrophy with enlarged ventricles have been described. The cerebellum seems to be spared.
Genetics
Inheritance
Homozygous or compound heterozygous mutations in the TRAPPC12 gene (2p25.3) were found in 3 children in 2 unrelated families with 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.