Early-onset hereditary spastic paraplegia: case report

Case presentation: Girl, 5 years old, she had not gestational and neonatal complications and her parents is consanguineous. She had neuropsychomotor developmental delay (NDD) and dysphagia for solids at 6 months. At 2 years old, she had cognitive impairment, motor delay with axial ataxia, appendicular hypotonia and dysmetria. Her symptoms progressively worsening associated with pyramidal signs. Cerebellar atrophy and increased arachnoid space in the posterior fossa were identified on her neuroimaging. Her whole genome sequencing identified a pathogenic variant c.395A>C,p.(Asp132Ala) in the EXOSC3 gene in homozygosity.

Discussion: The clinical features are compatible with Pontocerebellar hypoplasia (PCH) type 1B, autosomal recessive inheritance. Pathogenic variants in the EXOSC3 gene are responsible for 30% to 50% of patients with PHC. EXOSC3 gene associated PCH is characterized by abnormalities in the posterior fossa and degeneration of the anterior horn cells. At birth, the main clinical symptoms are hypotonia and poor feeding. Survival and symptom severity is variable and they depend on genotype. In this case, the onset of symptoms was in the first months of life with axial and appendicular hypotonia, dysphagia, early pyramidal and cerebellar signs and her survival was after early childhood. This case is classified as mild PCH after phenotype-genotype correlation and according to the report of other authors. However, it is important to note that the progression of spastic paraplegia may not have a favorable outcome.

Final comments: The phenotype of hereditary early-onset spastic paraplegia associated with the EXOSC3 gene was described in this report. Genetic tests are important for performing differential diagnosis for suspected cerebral palsy when there are no risk factors, in addition to prognostic guidance and genetic counseling.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
18 September 2023