The adult phenotype of Schaaf-Yang syndrome

• Published in: Orphanet journal of rare diseases 2020-10, Vol.15 (1), p.1-294, Article 294
• Main Authors: Marbach, Felix, Elgizouli, Magdeldin, Rech, Megan, Beygo, Jasmin, Erger, Florian, Velmans, Clara, Stumpel, Constance T. R. M, Stegmann, Alexander P. A, Beck-Wödl, Stefanie, Gillessen-Kaesbach, Gabriele, Horsthemke, Bernhard, Schaaf, Christian P, Kuechler, Alma
• Format: Article
• Language: English
• Subjects: Adult phenotype; Adults; Aggressiveness; Autism; Autonomy; Behavior; Body weight gain; Children; Data collection; Families & family life; Feeding behavior; Food habits; Food intake; Genetic aspects; Genetic screening; Genotype & phenotype; Glucose; Growth hormones; Guardians; Intellectual disabilities; MAGEL2; Medical research; Obesity; Phenotypes; Prader-Willi syndrome; Questionnaires; Rare diseases; Schaaf-Yang syndrome; Sleep; Sleep apnea; Social research; Withdrawal
• ISSN: 1750-1172; 1750-1172
• DOI: 10.1186/s13023-020-01557-8

MAGEL2-associated Schaaf-Yang syndrome (SHFYNG, OMIM #615547, ORPHA: 398069), which was identified in 2013, is a rare disorder caused by truncating variants of the paternal copy of MAGEL2, which is localized in the imprinted region on 15q11.2q13. The phenotype of SHFYNG in childhood partially overlaps with that of the well-established Prader-Willi syndrome (PWS, OMIM #176270). While larger numbers of younger individuals with SHFYNG have been recently published, the phenotype in adulthood is not well established. We recruited 7 adult individuals (aged 18 to 36) with molecularly confirmed SHFYNG and collected data regarding the clinical profile including eating habits, sleep, behavior, personal autonomy, psychiatric abnormalities and other medical conditions, as well as information about the respective phenotypes in childhood. Within our small cohort, we identified a range of common features, such as disturbed sleep, hypoactivity, social withdrawal and anxiety, but also noted considerable differences at the level of personal autonomy and skills. Behavioral problems were frequent, and a majority of individuals displayed weight gain and food-seeking behavior, along with mild intellectual disability or borderline intellectual function. Classical symptoms of SHFYNG in childhood were reported for most individuals. Our findings indicate a high variability of the functional abilities and social participation of adults with SHFYNG. A high prevalence of obesity within our cohort was notable, and uncontrollable food intake was a major concern for some caregivers. The phenotypes of PWS and SHFYNG in adulthood might be more difficult to discern than the phenotypes in childhood. Molecular genetic testing for SHFYNG should therefore be considered in adults with the suspected diagnosis of PWS, if testing for PWS has been negative.