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Table 2 Epigenetic hereditary traits contribution to developmental diseasesa

From: Epigenetic inheritance and the missing heritability

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)
  1. aPhenotype-genotype correlations were extracted from the OMIM databank (www.ncbi.nlm.nih.gov/omim)