SPG7-Related Neurologic Disorder

Excerpt

Clinical characteristics: The phenotypic spectrum of SPG7-related neurologic disorder includes uncomplicated spastic ataxia, complicated spastic ataxia, spinocerebellar ataxia, and isolated optic nerve atrophy. Although onset typically occurs in adulthood, it may start in infancy or as late as age 72 years. Initially the spastic paraplegia is typically characterized by insidiously progressive bilateral leg weakness and spasticity or cerebellar findings (ataxia, dysarthria, and dysphagia) or both. Other central nervous system findings include decreased visual acuity due to optic neuropathy, cognitive impairment, and dystonia. Peripheral nervous system involvement manifests as motor and sensory neuropathy, neuropathic pain, and amyotrophy. Associated musculoskeletal involvement includes pes cavus and scoliosis. Spasticity and ataxia are progressive and may result in wheelchair dependence.

Diagnosis/testing: The diagnosis of SPG7-related neurologic disorder is established in a proband with suggestive findings and biallelic pathogenic variants in SPG7 identified by molecular genetic testing.

Management: Treatment of manifestations: Multidisciplinary care by specialists in neurology, ophthalmology, low vision services, audiology, urology, physiatry, occupational therapy, physical therapy, orthopedics, feeding therapy and nutrition, speech-language therapy, social work, psychology, and clinical genetics.

Surveillance: Monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations with routinely scheduled evaluations by treating specialists.

Genetic counseling: SPG7-related neurologic disorder is inherited in an autosomal recessive manner. (Several studies have reported a single [heterozygous] pathogenic variant in SPG7 in individuals with SPG7-related neurologic disorder suggesting the possibility of autosomal dominant inheritance; however, the possibility of autosomal dominant inheritance remains controversial.) If both parents are known to be heterozygous for an SPG7 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being heterozygous, and a 25% chance of inheriting neither of the familial pathogenic variants. Once the SPG7 pathogenic variants have been identified in an affected family member, heterozygote testing for at-risk relatives and prenatal/preimplantation genetic testing for SPG7-related neurologic disorder are possible.