p.Arg499His mutation in SPAST associated with infantile-onset complicated spastic paraplegia in a child with bilateral retinoblastoma: association or coincidence?

Case presentation: Patient was the first child of non-consanguineous parents whose father healthy, but mother had mild intellectual deficiency and spastic paraparethic gait that been attributed to cerebral palsy. At birth he presented congenital talipes equinovarus. He began crawl at 1yo never able walk independently despite orthopedic feet correction. 1yo, leukocoria in left eye noticed. Bilateral retinoblastoma diagnosed by age 2y 9m. submitted primary bilateral enucleation confirmed extra-ocular undifferentiated retinoblastoma. 3yo it noticed prominent forehead, underdeveloped supraorbital ridges, low set ears, triangular shaped face, tongue protrusion, long hand fingers, axial hypotonia, upper limb lower hypertonia, oral hypotonia tendon reflexes were 4+ globally, with unsustained knee clonus extension hallux. emitted guttural sounds only partially obey commands. His MRI showed post-surgical manipulation status both orbits hippocampal rotation. A genetic panel revealed a heterozygous pathogenic missense variant, c.1496G>A (p.Arg499His), confirming autosomal dominant hereditary paraplegia 4 (SPG4) diagnostic.