Spastic Paraplegia 15

Excerpt

Clinical characteristics: Spastic paraplegia 15 (SPG15), typically an early-onset complex hereditary spastic paraplegia, is characterized by progressive spasticity that begins in the lower extremities and is associated with several manifestations resulting from central and peripheral nervous system dysfunction. While onset of spasticity is typically in mid- to late childhood or adolescence (i.e., between ages 5 and 18 years), other manifestations, such as developmental delay or learning disability, may be present earlier, often preceding motor involvement. Individuals with adult onset have also been reported.

Diagnosis/testing: The diagnosis of SPG15 is established in a proband with suggestive findings and biallelic pathogenic variants in ZFYVE26 identified by molecular genetic testing. Findings suggestive of SP15 on brain MRI may include thinning of the corpus callosum and characteristic signal changes in the periventricular white matter, known as the "ears of the lynx" sign.

Management: Treatment of manifestations: At present, no treatment prevents, halts, or reverses neuronal degeneration in SPG15. Treatment is directed at reducing symptoms and preventing secondary complications. Multidisciplinary care involving a neurologist, clinical geneticist, developmental specialist, orthopedic surgeon/physiatrist, physical therapist, occupational therapist, speech and language pathologist, and feeding and nutrition team is recommended.

Surveillance: Affected individuals should be evaluated periodically (i.e., every 6-12 months) by an interdisciplinary team to assess disease progression, maximize ambulation and communication skills, and reduce other manifestations.

Genetic counseling: SPG15 is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a ZFYVE26 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the ZFYVE26 pathogenic variants have been identified in an affected family member, prenatal and preimplantation genetic testing are possible.