Yutaka Negishi1, Daisuke Ieda1, Ikumi Hori1, Yasuyuki Nozaki2, Takanori Yamagata2, Hirofumi Komaki3, Jun Tohyama4, Keisuke Nagasaki5, Hiroko Tada6, Shinji Saitoh7. 1. Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-Cho, Mizuho-Ku, Nagoya, 467-8601, Japan. 2. Department of Pediatrics, Jichi Medical University, Tochigi, Japan. 3. Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan. 4. Department of Child Neurology, Nishi-Niigata Chuo National Hospital, Niigata, Japan. 5. Division of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. 6. Department of Pediatrics, Chibaken Saiseikai Narashino Hospital, Narashino, Japan. 7. Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-Cho, Mizuho-Ku, Nagoya, 467-8601, Japan. ss11@med.nagoya-cu.ac.jp.
Abstract
BACKGROUND: Schaaf-Yang syndrome (SYS) is a newly recognized imprinting related syndrome, which is caused by a truncating variant in maternally imprinted MAGEL2 located in 15q11-q13. Yet, precise pathomechanism remains to be solved. We sequenced MAGEL2 in patients suspected Prader-Willi syndrome (PWS) to delineate clinical presentation of SYS. We examined 105 patients with clinically suspected PWS but without a specific PWS genetic alteration. Sanger sequencing of the entire MAGEL2 gene and methylation-specific restriction enzyme treatment to detect the parent of origin were performed. Clinical presentation was retrospectively assessed in detail. RESULTS: Truncating variants in MAGEL2 were detected in six patients (5.7%), including a pair of siblings. All truncating variants in affected patients were on the paternally derived chromosome, while the healthy father of the affected siblings inherited the variant from his mother. Patients with MAGEL2 variants shared several features with PWS, such as neonatal hypotonia, poor suck, and obesity; however, there were also unique features, including arthrogryposis and a failure to acquire meaningful words. Additionally, an episode of neurological deterioration following febrile illness was confirmed in four of the six patients, which caused severe neurological sequalae. CONCLUSIONS: SYS can be present in infants suspected with PWS but some unique features, such as arthrogryposis, can help discriminate between the two syndromes. An episode of neurological deterioration following febrile illness should be recognized as an important complication.
BACKGROUND:Schaaf-Yang syndrome (SYS) is a newly recognized imprinting related syndrome, which is caused by a truncating variant in maternally imprinted MAGEL2 located in 15q11-q13. Yet, precise pathomechanism remains to be solved. We sequenced MAGEL2 in patients suspected Prader-Willi syndrome (PWS) to delineate clinical presentation of SYS. We examined 105 patients with clinically suspected PWS but without a specific PWS genetic alteration. Sanger sequencing of the entire MAGEL2 gene and methylation-specific restriction enzyme treatment to detect the parent of origin were performed. Clinical presentation was retrospectively assessed in detail. RESULTS: Truncating variants in MAGEL2 were detected in six patients (5.7%), including a pair of siblings. All truncating variants in affected patients were on the paternally derived chromosome, while the healthy father of the affected siblings inherited the variant from his mother. Patients with MAGEL2 variants shared several features with PWS, such as neonatal hypotonia, poor suck, and obesity; however, there were also unique features, including arthrogryposis and a failure to acquire meaningful words. Additionally, an episode of neurological deterioration following febrile illness was confirmed in four of the six patients, which caused severe neurological sequalae. CONCLUSIONS: SYS can be present in infants suspected with PWS but some unique features, such as arthrogryposis, can help discriminate between the two syndromes. An episode of neurological deterioration following febrile illness should be recognized as an important complication.
Authors: Dai Yang-Li; Luo Fei-Hong; Zhang Hui-Wen; Ma Ming-Sheng; Luo Xiao-Ping; Liu Li; Wang Yi; Zhou Qing; Jiang Yong-Hui; Zou Chao-Chun Journal: Orphanet J Rare Dis Date: 2022-06-13 Impact factor: 4.303