OMIM ID:
Spastic Paraplegia 15
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Yellowish flecks resembling those seen in fundus flavimaculatus are present, primarily in the macular area. These can be present in large numbers in homozygotes with the full neurological syndrome. Background retinal pigmentation appears clinically normal but fluorescein angiography shows a strikingly mottled picture with areas of hyper- and hypofluorescence. Retinal flecks have also been reported in heterozygous parents.
The central macula exhibits autofluorescence. Standard EOG and ERG recordings are normal but multifocal electroretinography shows subnormal responses in the macular area. Visual acuity is minimally impacted.
Systemic Features
This is a form of spastic paraplegia with progressive spasticity primarily affecting the lower limbs. Mental retardation (or at least cognitive impairment), dysarthria, a thin corpus callosum, and distal amyotrophy are often present. Hearing deficits have also been described. Some but not all patients have tremors, cerebellar ataxia, epilepsy and behavioral disturbances. Onset is between 10 and 19 years of age. Little is known about the rate of symptom progression.
Genetics
Inheritance
This is an autosomal recessive disorder resulting from mutations in the ZFYVE26 gene (14q24.1).
Spastic paraplegia 7 (607259) has similar neurological features but with ptosis, optic atrophy, and nystagmus. Congenital cataracts occur in addition to the neurological signs in spastic paraplegia 46 (614409) .
Other disorders with retinal flecks are described in Flecked Retina Syndromes.
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.