Hereditary spastic paraplegia masqueraded by congenital melanocytic nevus syndrome: Dual pathogenesis of germline non-mosaicism and somatic mosaicism

Neurocutaneous disorders are caused by germline and/or somatic mutations and involve the integument and central nervous systems. Congenital melanocytic nevus syndrome is characterized by melanotic skin lesions caused by somatic mutations at codon 61 in NRAS. A large cutaneous lesion raises the risk of central nervous system involvement. We report an 8-year-old girl with a congenital giant pigmented nevus that covered almost her entire back. Despite the absence of any radiological evidence of intracranial melanosis, the patient exhibited progressive limb spasticity with preserved intellectual ability. An extensive genetic analysis identified a specific class of heterozygous germline mutation in SPAST, p.(Arg499His), which is responsible for hereditary spastic paraplegia with infantile onset. In addition, a known heterozygous somatic mutation in NRAS, p.(Gln61Lys) was detected in the cutaneous lesion. This observation recapitulates concomitant mosaicism and non-mosaicism within a single individual and suggests that the possibility of a dual genetic diagnosis should be considered when neurological decline is observed in a patient with a neurocutaneous disorder without any detectable intracranial lesions.