Genetic basis:
• common form (60%): interstitial deletion of the paternally derived chromosome
• 30%: maternal uniparental disomy, with both abnormal genes maternally derived
• 10%: variety of microdeletions or point mutations
Clinical features:
(1) facial features:
(1a) almond-shaped eyes with antimongoloid slant
(1b) convergent squint (strabismus)
(1c) prominent epicanthic folds
(1d) narrow bifrontal diameter
(1e) cupid's-bow mouth with thin superior vermillion margin
(2) neonatal muscular hypotonia with poor sucking and feeding difficulties
(3) obesity starting in childhood, with possible morbid obesity in the adult
(4) hyperphagia and food seeking behavior
(6) behavioral problems starting in late childhood or adolescence, including obsessions, contrary behaviors, and habit disorders (skin picking, hair plucking, rectal picking, etc.)
(7) obstructive sleep apnea, with somnolescence during the day, occasionally progressing to cor pulmonale in the very obese
(8) mild-to-moderate mental retardation
(9) hypothalamic hypogonadism during late childhood and adolescence, with infertility
(10) short stature with small hands and feet
(11) poor muscle strength
Additional findings:
(1) isolated capabilities for achievement
(2) tenacious saliva
(3) high-pitched nasal voice
(4) hypothermia
(5) high pain threshold
(6) decreased bone density
(7) fair hair and skin color
(8) diabetes mellitus
Testing:
• high resolution chromosomes banding with FISH, using probes known to map within the region of 15q11q13
• methylation studies
