Schaaf–Yang syndrome (SYS) is a rare genetic disorder that is caused by a heterozygous mutation in a paternal-expressed gene MAGEL2. Main signs of this disorder are: intellectual disability/developmental delay, autism spectrum disorder, hypogonadism, hypotonia in infancy with feeding problems, and distal arthrogryposis. Facial features are included short noses, dense eyebrows, and protruding jaw.
Signs and symptoms Symptoms of this disease are: Very frequent
Facial shape abnormality Undescended testis Feeding problems Hypotonia Flexion contracture Neurodevelopmental delay Frequent
Visceral obesity Temper tantrums Lack of pubertal development Autistic behavior Chronic constipation External genital hypoplasia Borderline/Mild Intellectual disability Kyphosis Scoliosis Sleep apnea Temperature regulation problems Failure to thrive Gastroesophageal reflux disease Hypogonadism Enlargement of cerebral ventricles Occasional
Almond-shaped eyes Atrial septal defect Hypothyroidism Central sleep apnea Downturned corners of mouth Thin nasal bridge Thin upper lip Seizure Abnormal dryness of the mouth Type 2 diabetes
Cause The cause of this disease are mutation in a gene MAGEL2 which is located on chromosome 15 (15q11.2) and that gene is expressed from paternal chromosome 15 and methylated on maternal chromosome 15. The MAGEL2 is a part of regulatory complex MUST, which consist of MAGEL2-USP7-TRIM27. This complex regulates WASH complex which function is to promotes endosomal actin polymerization. 50% of people with SYS inherited mutation from their father and remainder are de novo mutation (which means that mutation is new and none of the parents have it). MAGEL2-regulated WASH complex is important for the regulated secretion in the hypothalamus. MAGEL2 mutation causes decreased secretion of hormones, such as: oxytocin, AVP, somatostatin, thyrotropin-releasing hormone, growth hormone, and luteinizing hormone. Loss of that protein also showed neuronal activity loss in the hypothalamus and hippocampus of mice by disruptions of neuronal activity and changes in the synaptic excitation/inhibition balance through AMPA receptor trafficking defects.
Diagnosis SYS can be suspected by symptoms and subsequently can be diagnosed by genetic testing.
Treatment SYS doesn't have a cure. Although symptomatic management is available, It might be effective but it still doesn't alleviate overall impact of SYS, which leaves caregivers unsatisfied.
Prognosis Life expectancy of person with SYS can be reduced due to fatal complication. Survival into adulthood is possible and oldest patient with SYS is 36 years olds (at the time of article's publication).
History The first mention of SYS-like symptoms was described by Chitayat et al. (1990). Although the name was coined by Christian P Schaaf and Yaping Yang, who described SYS in details in 2013.
Prevalence The prevalence of SYS is < 1/1,000,000. Currently, it is estimated that about 250 people are diagnosed with SYS.
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