1 - Serviço de Genética Médica, Hospital Dona Estefânia, Centro Hospitalar e Universitário de Lisboa Central, Lisboa, Portugal
2 - Serviço de Genética Médica, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
- European Human Genetics Virtual Conference 2021, virtual meeting, 28-31 de Augusto. Sob a forma de poster.
Resumo:
Introduction: Schuurs-Hoeijmakers Syndrome (SHS, OMIM #615009) is a rare cause of developmental delay with distinctive dysmorphic features. SHS is characterized by variable degrees of intellectual disability with language skills typically affected, hypotonia, epilepsy, behaviour issues, feeding difficulties, constipation, cryptorchidism, short stature, and structural malformations (cardiac, brain, ocular, kidney and skull anomalies). The majority of cases results from a de novo heterozygous
Methods: We inquired all Portuguese medical genetics departments, collected clinical data and compared with previous described cases.
Results: One patient, a 2-year-old male, presented with developmental delay, facial dysmorphisms, hypotonia, coloboma, cryptorchidism, plagiobrachycephaly and single umbilical artery. A second patient, a 4-year-old male, was referred for developmental delay, epilepsy, facial dysmorphisms, prenatal macrocephaly, congenital heart defect, cryptorchidism, umbilical hernia and prior history of constipation. In both cases, previous investigation was normal and molecular confirmation of SHS was obtained by exome sequencing that identified a de novo pathogenic variant in PACS1 c.607C>T p.(Arg203Trp).
The overall phenotypes were consistent with the reported cases, sharing the most frequent described clinical features such as dysmorphisms, intellectual disability, epilepsy, and congenital heart defects, but also less frequent features as umbilical hernia.
Conclusions: SHS is a distinct neurodevelopmental disorder with multiple congenital anomalies, and the identification of additional cases increases the current understanding of its clinical spectrum. To our knowledge, these cases represent the first molecular confirmed SHS patients in Portugal.
Palavras Chave: anomalias congénitas múltiplas, perturbação do neurodesenvolvimento, gene PACS, Síndrome de Schuurs-Hoeijmakers