RARS2 mutations in a sibship with infantile spasms

Area of Science:

• Genetics
• Neuroscience
• Developmental Biology

Background:

• Pontocerebellar hypoplasia (PCH) encompasses heterogeneous neurodevelopmental disorders.
• These conditions are defined by reduced brainstem and cerebellar volume.
• PCH type 6 (PCH6) is associated with mutations in the RARS2 gene.

Observation:

• Two male siblings presented with infantile clonic seizures.
• They later developed infantile spasms.
• Magnetic resonance imaging (MRI) revealed prominent isolated cerebellar hypoplasia/atrophy.

Findings:

• Whole exome sequencing identified compound heterozygous mutations in RARS2.
• One mutation was previously reported, and one was novel.
• This expands the known genotype-phenotype correlations for RARS2 mutations.

Implications:

• The findings broaden the electroclinical spectrum of PCH6.
• Infantile spasms are identified as a potential associated phenotype.
• This research aids in understanding PCH heterogeneity and RARS2-related disorders.