OMIM ID:
Spinocerebellar Ataxia, Autosomal Recessive 7
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Nystagmus and saccadic pursuit eye movements are common signs. Some patients complain of diplopia. No other ocular abnormalities are present.
Systemic Features
Symptoms have their onset in late childhood and are slowly progressive. Walking and balancing are difficult. Dysarthria, postural tremor, and limb ataxia are evident in adults. Fine motor movements are difficult and there is often a tremor in the hands. Deep tendon reflexes are abnormally brisk and extensor plantar responses are seen in some individuals. Vibration sense may be diminished. These signs are variable as is the rate of progression. Usually patients remain mobile and productive through the fourth decade of life. They may become wheelchair-bound by the fifth or sixth decade. There is no cognitive impairment.
Genetics
Inheritance
This is an autosomal recessive condition secondary to homozygous mutations in TPP1(11p15).
The same gene is mutated in neuronal ceroid lipofuscinosis 2 (CLN2, 204500), a far more serious condition with epilepsy, optic atrophy, retinal degeneration, and a rapidly progressive course leading to early death in many individuals. It has been suggested that mutations resulting in the more severe CLN2 phenotype completely or nearly completely abolish TPP1 enzyme activity whereas those that cause SCAR7 simply result in diminished activity.
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.