Multiple phenotypic traits including developmental impairment in a Chinese family with infantile convulsion and choreoathetosis syndrome: a case study expanding the clinical spectrum of prrt2-related syndrome.

BACKGROUND: Pathogenic heterozygous variants in the gene encoding proline-rich transmembrane protein 2 (PRRT2) have been recently identified as the major cause of familial infantile convulsion and choreoathetosis syndrome (OMIM#602,066), a spectrum of autosomal dominant paroxysmal neurological disorders, including self-limited infantile epilepsy (SeLIE) and infantile convulsion that can be isolated (IC) or associated with paroxysmal kinesigenic dyskinesia (PKD/IC). Incomplete penetrance of PRRT2 variants and variable phenotypes without developmental impairment have been widely reported in previous studies of this syndrome, but no studies to date have documented global development delay (GDD) with growth retardation (GR) occurred in a family with multiple phenotypes of this syndrome. CASE PRESENTATION: Here, using family-based whole-exome sequencing, we identified a pathogenic heterozygous PRRT2 variant (NM_145239.3: c.718C > T, p.Arg240*) in a 3-generation Chinese family of infantile convulsion and choreoathetosis syndrome. The variant was detected in five family members, of which two (pedigree III.1 and III.3) were diagnosed with PKD/IC, one (pedigree III.2) presented uncontrolled generalized/focal seizures with GDD and GR; the GR of this patient was aggravated with the progression of the epileptic condition; she was then diagnosed with IC and developmental impairment, one (pedigree II.2) was diagnosed with SeLIE, and one (pedigree II.3) was phenotypically unaffected and recognized as an obligate carrier. CONCLUSIONS: In conclusion, we reported a PRRT2-related syndrome family harboring multiple phenotypic features, including uncontrolled seizures with developmental impairment, which may potentially expand PRRT2-related clinical spectrum. Moreover, our findings suggest that children with PRRT2-related seizures/convulsions, especially those who suffer from uncontrolled multiple seizure types, should be aware of potential risks of having developmental impairment aggravation and need timely and effective antiepileptic medications.