Schaaf–Yang syndrome
Schaaf–Yang syndrome 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
- Delay of Neurodevelopment
- Visceral obesity
- Temper tantrums
- Eye problems
- Lack of pubertal development
- Unusual behaviour
- Autistic behaviour
- Chronic constipation
- External genital hypoplasia
- Borderline/Mild Intellectual disability
- Kyphosis
- Scoliosis
- Sleep apnea
- Squint eye
- Temperature regulation problems
- Failure to thrive
- Gastroesophageal reflux disease
- Hypogonadism
- Enlargement of cerebral ventricles
- 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 II diabetes
Cause
The cause of this disease are mutation in a gene MAGEL2 which is located on chromosome 15 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.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.