OMIM ID:
Kufor-Rakeb Syndrome
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Most patients have a supranuclear gaze paresis. Patients later may have dystonic oculogyric spasms.
Systemic Features
This is a rapidly progressive neurodegenerative disorder with juvenile onset. First signs of Parkinisonism are evident between the ages of 12 and 16 years of age. Within a year of onset severe motor handicaps develop along with some degree of dementia with aggression and visual hallucinations. Cognitive decline is often a feature. Fine tremors in the chin may be seen along with other extrapyramidal signs but these are not prominent in the limbs. Instead there is often rigidity and bradykinesia. Dysphagia, dysarthria, and ataxia are features in many patients. Peripheral sensory neuropathy and anosmia are present in some individuals.
Brain imaging often reveals generalized atrophy of the cerebellum, cerebral cortex, and brainstem.
Genetics
Inheritance
This condition results from homozygous or compound heterozygous mutations in the ATP13A2 gene (1p36.13).
Biallelic mutations in the same gene are also responsible for spastic paraplegia 78 (617225) with somewhat similar clinical features except for the general absence of Parkinsonism.
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.