ANUÁRIO DO HOSPITAL
DONA ESTEFÂNIA

1 - Serviço de Genética Médica, Hospital Dona Estefânia, Centro Hospitalar Universitário Lisboa Central, Lisboa
2 - Serviço de Genética Médica, Hospital Pediátrico, Centro Hospitalar Universitário de Coimbra, Coimbra
3 - Centro de Diagnóstico Pré-Natal, Maternidade Alfredo da Costa, Centro Hospitalar Universitário Lisboa Central, Lisboa

- Annual Meeting Sociedade Portuguesa de Genética Humana 2021 (Poster)

Introduction
Schaaf-Yang syndrome (SYS) (OMIM 615547) is an imprinted hereditary disease caused by pathogenic variants at MAGEL2 gene.
SYS is characterized by neonatal hypotonia, feeding difficulties, global developmental delay, joint contractures and respiratory distress. A minority of cases can be particularly hazardous.
Case Report
Healthy nonconsanguineous couple, with a healthy 9-year-old girl and previous termination of pregnancy at 18^th week of gestation (wog) due to fetal akinesia, cardiac and renal defects, bilateral overlapping digits, rocker-bottom feet and cystic hygroma in a male fetus. Was referred to our outpatient clinic during third pregnancy at 28^th wog, due to fetal akinesia, bilateral hydronephrosis, megacystis, polyhydramnios, retrognathia, overlapping left-hand digits, rocker-bottom feet and arthrogryposis in a female fetus. At 29 wog, a stillbirth was born. Fetal whole exome sequencing analysis detected a heterozygous pathogenic variant c.1996del p. (Gln666Serfs*36) at MAGEL2, segregation studies concluded inheritance from unaffected father, establishing SYS diagnosis. Molecular study of previous fetus was requested, and the same variant was present.
Discussion:
MAGEL2 is located in the Prader-Willi critical region 15q11-13. Pathogenic variants in the maternally imprinted/paternally expressed MAGEL2 gene present variable phenotypes, from mild contractures to fetal death. The imprinted nature of this condition can phenotypically skip generations if the mutation resides on the maternal chromosome. Male carriers of a MAGEL2 pathogenic variant have a 50% chance of having an affected child. Literature review reports 6 cases with c.1996delC pathogenic variant at MAGEL2. All cases resulted in fetal or perinatal death, due to severe arthrogryposis and fetal akinesia. These findings were consistent with our case report, and highlight the severity of this variant, bringing to attention the importance of parental testing, determination of the allelic location of the variant and the challenges for genetic counseling when imprinting disorders are present.

Palavras Chave: Imprinting disorders, Prenatal diagnosis, Schaaf-Yang syndrome