OMIM ID:
Neurodevelopmental Disorder with Progressive Microcephaly, Spasticity, and Brain Anomalies
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Examined patients have optic atrophy with nystagmus and roving eye movements.
Systemic Features
There are extensive and, in most cases, progressive CNS abnormalities resulting in severe neurodevelopmental deficits. Infants at birth have progressive truncal hypotonia and limb spasticity. Motor deficits result in little spontaneous movement, resulting in poor sucking, and respiratory difficulties. Language does not develop and there is profound mental retardation. Progressive microcephaly is a characteristic finding. There are often extrapyramidal signs such as rigidity and dystonic posturing.
Dysmorphic features include a short nose, high-arched palate, low-set and posteriorly rotated ears, micrognathia, postaxial polydactyly, hirsutism, pectus carinatum, contractures of large joints, and hyperextensibility of small joints.
Brain imaging shows a progressive leukoencephalopathy, cerebral and cerebellar atrophy, and delayed myelination. The corpus callosum is often thin and the ventricles appear enlarged. The lifespan is generally short with death occurring in infancy or early childhood.
Genetics
Inheritance
This autosomal recessive disorder results from homozygous mutations in the PLAA gene (9p21).
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.