OMIM ID:
Spastic Paraplegia 5A
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Gaze-evoked nystagmus and saccadic pursuit movements are present in about 10% of patients. Optic atrophy was reported in one individual. Rare patients have been reported to have cataracts.
Systemic Features
This is a progressive disorder of neurological deterioration. Age of onset (mean 16.4 years) and rate of neurological dysfunction are highly variable. Gait difficulties are the most common presenting signs. Some gait ataxia is usually present. The lower limbs are more severely affected by spasticity and weakness and walking is often delayed with difficulty running and clumsiness in childhood. Some patients (38%) are wheelchair-bound after disease duration of more than 33 years. Dysphagia and dysarthria are uncommon.
Some sensory impairments such as impaired vibratory sense, decreased proprioception, and absent touch sensation in the lower extremities are frequently present. Urge incontinence of bladder and rectum is sometimes a feature.
Genetics
Inheritance
Bialllelic mutations in the CYP7B1 gene (8q12.3) have been identified in this disorder resulting in a marked accumulation of neurotoxic oxysterols in plasma and CSF.
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.