OMIM ID:
Spastic Paraplegia with Psychomotor Retardation and Seizures
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The eyes are usually deeply set. Nothing is known regarding visual acuity. Strabismus is a common feature. Retinal dystrophy (not further described) has been reported in 4 of 8 patients described. The ERG in one individual was read as consistent with cone-rod dystrophy.
Systemic Features
Newborns are hypotonic and severe psychomotor retardation is evident a few months later. Truncal ataxia and progressive lower limb spasticity are seen later. Mobility is significantly impaired and many individuals are confined to bed or a wheelchair and never walk. Dysarthria is frequently present and some individuals have a neurosensory hearing loss. Myoclonic seizures may be evident. Kyphoscoliosis, macrocephaly, and various foot deformities have been described.
CT scans of the brain may show generalized cerebral atrophy and a hypoplastic corpus callosum. The ventricles may be enlarged and the EEG confirms the occurrence of myoclonic as well as tonic-clonic and focal epilepsy.
Genetics
Inheritance
This is an autosomal recessive disorder caused by homozygous or compound heterozygous mutations in the HACE1 gene (6q16).
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.