Spastic Quadriplegia Resulting From a Pathogenic Variant in the SPAST Gene: A First Report

The SPAST gene encodes spastin, a microtubule-severing protein. Pathogenic variants in this gene are commonly associated with autosomal dominant Spastic paraplegia type 4 (SPG4), a neurodegenerative disorder presenting with progressive lower limb spasticity. Severe phenotypes involving more extensive neurological impairment are rare.

We report the first known case of an adolescent with a rare pathogenic SPAST variant (NM_014946.4: c.1507C > T; NP_055761.2: p. [Arg503Trp]) presenting with spastic quadriplegia. Additional features included severe intellectual disability, absent speech, dysphagia, and epilepsy, manifestations infrequently reported in association with SPAST mutations. He was born prematurely at 32 weeks of gestation after a complicated antenatal period due to the development of preeclampsia at 23 weeks and gestational diabetes mellitus at 26 weeks.

The patient's clinical presentation represents one of the most severe phenotypes described in the literature for SPAST-related disorders. The identification of a genetic cause provided a more satisfactory and specific diagnosis than the previously presumed etiology of perinatal asphyxia. This case broadens the phenotypic spectrum of SPAST-related disease and highlights the role of genetic testing in the diagnostic workup of complex neurological conditions.

We report the first case of a pathogenic variant in the SPAST gene and quadriplegia and one of the most severe clinical phenotypes described in the literature in association with variants in this gene. This report underscores the importance of considering SPAST mutations in patients with atypical or severe neurodevelopmental presentations. Genetic diagnosis enables more accurate prognosis, individualized medical care, and appropriate genetic counseling for families.