Non-cancerous syndromes | Phenotypes/clinical features | Molecular defects |
---|---|---|
ATR-X | Upswept frontal hair line; hypertelorism; epicanthic folds; flat nasal bridge; small triangular upturned nose; tented upper lip; everted lower lip; hypotonic facies | Mutations in ATRX gene, hypomethylation of specific repeat and satellite sequences |
Fragile X | Mild to severe intellectual disabilities; elongated face; large or protruding ears; macroorchidism; stereotypic movements (e.g., hand-flapping); social anxiety | Expansion and methylation of CGG repeat in FMR1 5′UTR, promoter methylation |
ICF | Hypertelorism; low-set ears; epicanthal folds; macroglossia | DNMT3B mutations, DNA hypomethylation |
Angelman | Severe intellectual and developmental disabilities; sleep disturbance; seizures; jerky movements (e.g., hand-flapping); frequent laughter or smiling; a happy behavior | Deregulation of one or more imprinted genes at 15q11–13 (maternal) |
Prader–Willi | Low muscle tone; short stature; incomplete sexual development; cognitive disabilities; chronic feeling of hunger leading to excessive eating and life-threatening obesity | Deregulation of one or more imprinted genes at 15q11–13 (paternal) |
Beckwith–Wiedemann | Macroglossia; macrosomia; midline abdominal wall defects; ear creases or ear pits; neonatal hypoglycemia | Deregulation of one or more imprinted genes at 11p15.5 (e.g., IGF2) |
Rett | Small hands and feet; decelerated rate of head growth; repetitive stereotyped hand movements (e.g., wringing and/or repeatedly putting hands into the mouth); gastrointestinal disorders; seizures; no verbal skills; scoliosis; growth failure; constipation | MeCP2 mutations |
Rubinstein–Taybi | Short stature; moderate to severe learning difficulties; broad thumbs and first toes; increased risk of developing benign and malignant tumors, leukemia, and lymphoma | Mutation in CREB-binding protein (histone acetylation) |
Coffin–Lowry | Abnormal growth; cardiac defects; kyphoscoliosis; auditory and visual abnormalities | Mutation in Rsk-2 (histone phosphorylation) |
Silver–Russel | Feeding problems; hypoglycemia; excessive sweating; triangular shaped face with a small jaw and a pointed chin that tends to lessen slightly with age; curved down mouth; blue tinge to the whites of the eyes in younger children; normal size of head circumference, disproportionate to a small body size; wide and late-closing fontanelle; clinodactyly; body asymmetric growth; precocious puberty; low muscle tone; gastroesophageal reflux disease; lack of subcutaneous fat; late closing of the opening between the heart hemispheres; constipation | Loss of methylation on the ICR1 paternal allele at the H19/IGF2 locus (11p15) |