The role of obesity in the fatal outcome of Schaaf–Yang syndrome: Early onset morbid obesity in a patient with a MAGEL2 mutation

Schaaf–Yang syndrome (SYS) was recently identified as a genetic condition resembling Prader–Willi syndrome. It is caused by mutations on the paternal allele of the MAGEL2 gene, a gene that has been mapped in the Prader–Willi critical region. Here, we present an infant with SYS who sadly died because of the combination of hypotonia, sleep apnea, and obesity. A heterozygous premature stop mutation in MAGEL2 was identified in the patient. The main factors reported in the mortality of SYS are lethal arthrogryposis multiplex congenita, fetal akinesia, and pulmonary problems. Our clinical report indicates that obesity and its complications are an important additional factor in the mortality associated with SYS. Therefore, we advise to strictly monitor weight and intensively treat overweight and obesity in SYS.

[1]  A. Bayat,et al.  Chronic intestinal pseudo-obstruction syndrome and gastrointestinal malrotation in an infantwith schaaf-yang syndrome - Expanding the phenotypic spectrum. , 2018, European journal of medical genetics.

[2]  A. Latos-Bieleńska,et al.  Phenotype of two Polish patients with Schaaf–Yang syndrome confirmed by identifying mutation in MAGEL2 gene , 2018, Clinical dysmorphology.

[3]  S. Scherer,et al.  Chitayat-Hall and Schaaf-Yang syndromes:a common aetiology: expanding the phenotype of MAGEL2-related disorders , 2018, Journal of Medical Genetics.

[4]  Yajian Wang,et al.  Whole-exome Sequencing Helps the Diagnosis and Treatment in Children with Neurodevelopmental Delay Accompanied Unexplained Dyspnea , 2018, Scientific Reports.

[5]  N. Matsumoto,et al.  Three patients with Schaaf–Yang syndrome exhibiting arthrogryposis and endocrinological abnormalities , 2018, American journal of medical genetics. Part A.

[6]  C. Schaaf,et al.  Hormonal, metabolic and skeletal phenotype of Schaaf-Yang syndrome: a comparison to Prader-Willi syndrome , 2018, Journal of Medical Genetics.

[7]  J. Tavernier,et al.  The Prader-Willi syndrome proteins MAGEL2 and necdin regulate leptin receptor cell surface abundance through ubiquitination pathways , 2017, Human molecular genetics.

[8]  C. L. le Roux,et al.  Morbidity and mortality associated with obesity. , 2017, Annals of translational medicine.

[9]  J. Opitz,et al.  A De Novo Nonsense Mutation in MAGEL2 in a Patient Initially Diagnosed as Opitz-C: Similarities Between Schaaf-Yang and Opitz-C Syndromes , 2017, Scientific Reports.

[10]  J. Rosenfeld,et al.  The phenotypic spectrum of Schaaf-Yang syndrome – 18 new affected individuals from 14 families , 2016, Genetics in Medicine.

[11]  I. Gut,et al.  Truncating Mutations of MAGEL2, a Gene within the Prader-Willi Locus, Are Responsible for Severe Arthrogryposis. , 2015, American journal of human genetics.

[12]  Xuan Yuan,et al.  Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders , 2014, Science Translational Medicine.

[13]  B. Peters,et al.  Truncating mutations of MAGEL2cause Prader-Willi phenotypes and autism , 2013, Nature Genetics.

[14]  S. Isono.  Obstructive Sleep Apnea of Obese Adults: Pathophysiology and Perioperative Airway Management , 2009, Anesthesiology.

[15]  D. J. Driscoll,et al.  Prader-Willi syndrome. , 1984, Current problems in pediatrics.