Patients with SPG23 show a conglomeration of clinical features such as cognitive impairment child-onset spastic paraplegia micrognathia, thin faces, patchy vitiligo, and other pigmentary abnormalities. The latter feature includes premature graying of body hair.
Three patient sibs (two brothers and one sister) were described by Abdallat et al. (1980) and Lison et al. (1981). These patients were born to first-cousin consanguineous parents. All patients had progressive spastic paraparesis and peripheral neuropathy, as well as disordered skin and hair pigmentation, including vitiligo, hyperpigmentation, numerous lentigines, and premature graying of body hair. Sural nerve biopsy showed axonal degeneration; skin biopsy showed abnormal epidermal pigmentation. The proband had diffusely depigmented hair and skin at birth. From the age of 6 months, patchy pigmentation developed, especially in exposed areas of the skin, and his hair developed irregular pigmentation. Progressive paraparesis was first noted at age 6 years. The face was thin with sharp features.
Farag et al. (1993) conducted a clinicogenetic assessment of 400 institutionalized mentally retarded (IQ less than 50) Kuwaiti patients during a 4-year period (1986-1990). One of the patients was found to be suffering from Lison syndrome.
Mukamel et al. (1985) described an inbred Palestinian family with four affected sibs, which have been followed up later by Blumen et al. (2003). All these sibs suffered severe disabling spastic paraparesis from early childhood, combined with abnormalities of skin and hair pigmentation. Blumen et al. (2003) performed a genome-wide linkage screen and managed to link SPG23 to a region of 25-cM on 1q24-q32 with a peak LOD score of 3.05. Molecular analysis showed allele homozygosity in all affected individuals.