TY - JOUR
T1 - Schaaf-Yang syndrome overview
T2 - Report of 78 individuals
AU - McCarthy, John
AU - Lupo, Philip J.
AU - Kovar, Erin
AU - Rech, Megan
AU - Bostwick, Bret
AU - Scott, Daryl
AU - Kraft, Katerina
AU - Roscioli, Tony
AU - Charrow, Joel
AU - Schrier Vergano, Samantha A.
AU - Lose, Edward
AU - Smiegel, Robert
AU - Lacassie, Yves
AU - Schaaf, Christian P.
N1 - Publisher Copyright:
© 2018 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc.
PY - 2018/12
Y1 - 2018/12
N2 - Schaaf-Yang Syndrome (SYS) is a genetic disorder caused by truncating pathogenic variants in the paternal allele of the maternally imprinted, paternally expressed gene MAGEL2, located in the Prader-Willi critical region 15q11-15q13. SYS is a neurodevelopmental disorder that has clinical overlap with Prader-Willi Syndrome in the initial stages of life but becomes increasingly distinct throughout childhood and adolescence. Here, we describe the phenotype of an international cohort of 78 patients with nonsense or frameshift mutations in MAGEL2. This cohort includes 43 individuals that have been reported previously, as well as 35 newly identified individuals with confirmed pathogenic genetic variants. We emphasize that intellectual disability/developmental delay, autism spectrum disorder, neonatal hypotonia, infantile feeding problems, and distal joint contractures are the most consistently shared features of patients with SYS. Our results also indicate that there is a marked prevalence of infantile respiratory distress, gastroesophageal reflux, chronic constipation, skeletal abnormalities, sleep apnea, and temperature instability. While there are many shared features, patients with SYS are characterized by a wide phenotypic spectrum, including a variable degree of intellectual disability, language development, and motor milestones. Our results indicate that the variation in phenotypic severity may depend on the specific location of the truncating mutation, suggestive of a genotype–phenotype association. This evidence may be useful in both prenatal and pediatric genetic counseling.
AB - Schaaf-Yang Syndrome (SYS) is a genetic disorder caused by truncating pathogenic variants in the paternal allele of the maternally imprinted, paternally expressed gene MAGEL2, located in the Prader-Willi critical region 15q11-15q13. SYS is a neurodevelopmental disorder that has clinical overlap with Prader-Willi Syndrome in the initial stages of life but becomes increasingly distinct throughout childhood and adolescence. Here, we describe the phenotype of an international cohort of 78 patients with nonsense or frameshift mutations in MAGEL2. This cohort includes 43 individuals that have been reported previously, as well as 35 newly identified individuals with confirmed pathogenic genetic variants. We emphasize that intellectual disability/developmental delay, autism spectrum disorder, neonatal hypotonia, infantile feeding problems, and distal joint contractures are the most consistently shared features of patients with SYS. Our results also indicate that there is a marked prevalence of infantile respiratory distress, gastroesophageal reflux, chronic constipation, skeletal abnormalities, sleep apnea, and temperature instability. While there are many shared features, patients with SYS are characterized by a wide phenotypic spectrum, including a variable degree of intellectual disability, language development, and motor milestones. Our results indicate that the variation in phenotypic severity may depend on the specific location of the truncating mutation, suggestive of a genotype–phenotype association. This evidence may be useful in both prenatal and pediatric genetic counseling.
KW - MAGEL2
KW - Schaaf-Yang syndrome
KW - autism spectrum disorder
KW - genotype–phenotype association
KW - neurodevelopment
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U2 - 10.1002/ajmg.a.40650
DO - 10.1002/ajmg.a.40650
M3 - Article
C2 - 30302899
AN - SCOPUS:85054566811
SN - 1552-4825
VL - 176
SP - 2564
EP - 2574
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 12
ER -