Table 1 Major genetic imprinting disorders in humans

Prader–Willi syndrome (OMIM 176,270)

1/30,000–1/10,000

Neonatal hypotonia and poor suck, childhood-onset hyperphagia and severe obesity, developmental delay, hypogonadism, cognitive impairment, behavioral problems [37]

15q11–q13 (SNRPN, SNORD116)

Paternal deletion (65–70%), matUPD15 (20–30%), imprinting defect (1–5%)

Angelman syndrome (OMIM 105,830)

1/24,000–1/12,000

Developmental delay, severe intellectual disability, behavioral profile with happy demeanor, gait ataxia, microcephaly, seizure, characteristic electroencephalography [38]

15q11–q13 (UBE3A)

Maternal deletion (70–75%), gene mutation (5–10%), patUPD15 (1–2%), imprinting defects (1–3%)

Beckwith–Wiedemann syndrome (OMIM 130,650)

1/13,700–10,000

Pre/postnatal overgrowth, placental overgrowth, neonatal hypoglycemia, macroglossia, abdominal wall defects, predisposition to embryonal tumors [39]

11p15.5 (IGF2, CDKN1C)

Hypermethylation of H19/IGF2:IG-DMR causing biallelic expression of IGF2; hypomethylation of KCNQ1OT1:TSS-DMR causing CDKN1C silence, patUPD11, CDKN1C mutations

Silver–Russell syndrome (OMIM 180,860)

1/100,000–1/30,000

Severe IUGR, postnatal growth retardation, dysmorphism [40]

7p11.2 (MEST, GRB10)

MatUPD7 (5–10%), chromosomal rearrangements

11p15.5 (IGF2, H19)

Paternal hypomethylation (35–65%), matdup11p15, gene mutations

Pseudohypoparathyroidism type 1a (OMIM 103,580)

Unknown

Resistance to parathyroid hormone (hypocalcemia and hyperphosphatemia), abnormal growth patterns, dysmorphism, obesity, cognitive impairment

20q13 (GNAS)

Maternal inactivating gene mutations of GNAS

Pseudohypoparathyroidism 1b (OMIM 603,233)

Resistance to parathyroid hormone (hypocalcemia and hyperphosphatemia)

Maternal deletions, methylation defects within the GNAS complex locus, patUPD20

Transient neonatal diabetes mellitus (OMIM 601,410)

1/300,000

Neonatal hyperglycemia and IUGR

6q24 (PLAGL1, HYMAI)

PatUPD6 (40%), paternal duplication (32%), methylation defects (28%)

Temple syndrome (maternal UPD 14 syndrome) (OMIM 616,222)

Unknown

Prenatal and postnatal growth retardation, characteristic facies, premature puberty, obesity [41]

14q32 (DLK1, RTL1/GTL2)

MatUPD14, paternal deletion, aberrant methylation,

Kagami–Ogata syndrome (paternal UPD 14 syndrome) (OMIM 608,149)

Unknown

Polyhydramnios, placentomegaly, mental retardation, abdominal wall defects, dysmorphism [42]

PatUPD14, maternal deletion, aberrant methylation

Schaaf–Yang syndrome (OMIM 615,547)

Unknown

Developmental delay, intellectual disability, hypotonia, feeding difficulties, autism spectrum disorder [23]

15q11.2 (MAGEL2)

Paternal truncating gene mutations (100%)