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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)