A rare case of the complex phenotype of hereditary spastic paraparesis due to a mutation in a novel gene variant

Abstract

Hereditary spastic paraplegia (HSP), is a heterogeneous group of corticospinal tract disorders leading to progressive lower limb weakness and spasticity. Recessive mutations in DDHD2 characteristically involve early onset delay in motor and cognitive milestones coupled with spasticity. The complex nature of HSP is always confounding for appropriate management. An 11-year-old boy was brought by his parents for developmental delay noticed from 7 months of age and was diagnosed to have possible spastic cerebral palsy initially. Due to increasing spasticity, he underwent tendon release surgery for achilles and iliopsoas at 4 years of age. Now, he presented to us with increasing stiffness in his lower limbs even after regular physical therapy and myoclonic jerks. He had severe spasticity in the lower limbs with a power of 4/5. His activities of daily living were restricted due to severe spasticity. The lower limb deep tendon reflexes are exaggerated with positive Babinski sign and Scissoring of gait. He also had a mild intellectual disability. He was started on symptomatic management with muscle relaxants. Clinical exome sequencing showed a novel homozygous nonsense variation in exon 6 of DDHD2 gene. Prenatal genetic counseling was given for the next pregnancy and hence chorionic villus sampling for the variant testing of the developing fetus was done. The reports revealed a heterozygous state and asymptomatic carrier, unlikely to be affected by DDHD2-associated phenotype (spastic paraplegia genes 54). HSP should be considered when there is global developmental delay and increasing spasticity in lower limbs despite rehabilitation therapies.