A family with hereditary cerebellar ataxia finally confirmed as Gerstmann-Straussler-Scheinker syndrome with P102L mutation in PRNP gene

Abstract

Gerstmann-Straussler-Scheinker syndrome (GSS) is an exceedingly rare prion disease. There are only 3 case reports of GSS in China. Here we report the first GSS family in southern China. A 47-year-old female complained of unsteady gait and dysarthria. Seven other individuals presented similar symptoms in 3 generations of her family, and all died 4-6 years after onset. To detect causative mutations, we employed a gene analysis panel of hereditary diseases. This revealed a P102L mutation in the prion protein gene (PRNP) gene, which is commonly found in GSS featuring cerebellar ataxia. However, GSS is an uncommon cause of hereditary cerebellar ataxia that might be overlooked because many neurologists are unfamiliar with it. To avoid misdiagnosis in the patients with hereditary cerebellar ataxia, GSS should be taken into account if other causes are absent, especially in patients that have accompanying psychiatric symptoms and a short survival time.

Figure 1

- Family tree of the pedigree. Eight members across 3 generations were involved. All have died been dead except the proband.

Figure 2

- Magnetic resonance imaging (MRI) of the brain and spinal cord. Brain MRI showed existence of cavum vergae long arrow on panel (A), and relatively deep sulcuses short arrow on panels (A and B) suggesting mild diffuse brain atrophy (A, B). Intervertebral herniation in cervical 5/6 (C5/6) long arrow on panels (C and D) and C6/7 short arrow on panel (C) was detected by cervical spinal cord MRI, with mild degeneration of the associated spinal cord.

Figure 3

- Gene mapping of the patient. A missense mutation (C to T) was identified at nt 305 in one allele of the prion protein gene (PRNP), leading to a proline (Pro) to leucine (Leu) change at codon 102.