To highlight the wide clinical range of symptomatology for a family with SPG7 autosomal recessive mutation

To emphasize the utility of genetic testing in reaching a diagnosis of hereditary spastic paraperesis

Hereditary spastic paraplegia (SPG) is characterized by progressive weakness and spasticity of the lower limbs secondary to degeneration of the corticospinal axons. The condition is caused by a homozygous or compound heterozygous mutation in the paraplegin gene (SPG7; 602783) on chromosome 16q24.

Case Series:

We report a family from the North-West of Ireland with autosomal recessive SPG7, (c.1529C>T; p.Ala510Val) familial heterozygous variant.  The six affected family members presented with a broad spectrum of symptoms and variation in age of onset:

• Female sibling age 69 with a 12 year history of ataxia with gradual deterioration
• Female sibling age 67 with gait disturbance and lower limb rigidity suspected to have Parkinson’s disease
• Female sibling age 65 with a steady gait and facial dystonia
• Male sibling age 63 with ataxia
• Female sibling age 61 with mild balance issues
• Male sibling age 52 with gait difficulties and lower limb stiffness

Genetic testing has been carried out on 4 family members to date and confirms the presence of a heterozygous mutation in the paraplegin gene; SPG7.

The gene SPG7 encodes the protein paraplegin; an ATP-dependent proteolytic complex subunit, located at the inner mitochondrial membrane.  The protein complexes acts by regulating ribosomal activity and degrades misfolded proteins. An SPG7 follows an autosomal recessive mode of inheritance typically with variable clinical phenotypes as demonstrated by this family with 6 affected siblings (1).

This case series describes a wide-ranging clinical spectrum which is attributed to the SPG7 gene mutation.