Table 1 Overview on the molecular findings in the currently known IDs and their clinical characteristics

Transient Neonatal Diabetes Mellitus (TNDM)

1/300.000

601410

6q24: PLAGL1: alt-TSS

upd(6)pat

40 %

<1 %

IUGR, transient diabetes, hyperglycemia without ketoacidosis, macroglossia, omphalocele

paternal duplications

40 %

No

Up to 50 %

methylation defects

20 %

~50 %

Yes

<1 %

Upd(6)mat

Unknown

Chromosome 6, 6q16.1qter

upd(6)mat

Yes

Unknown

Silver-Russell syndrome (SRS; Russell-Silver Syndrome, RSS)

1/75.000-1/100.000

180860

7

upd(7)mat

~10 %

1 case^a

No

<1 %

IUGR/PNGR, small prematurely calcified placenta, rel. macrocephaly at birth, hemihypotrophy, prominent forehead, triangular face, feeding difficulties

11p15:

upd(11p15)mat

single case

Unknown

Rare

Genome-wide uniparental diploidy

single case

Yes

Rare

maternal duplication

<1 %

No

Up to 50 %

H19/IGF2: IG DMR

hypomethylation

>38 %^a

7-10 %

Yes

<1 %

CDKN1C

point mutations

1 family reported

No

In familial cases: up to 50 % in case of maternal transmission

IGF2

point mutations

1 family reported

No

Beckwith-Wiedemann syndrome (BWS; Wiedemann-Beckwith syndrome, EMG)

1/15.000

130650

11p15:

upd(11p15)pat

~20 %

Yes

<1 %

Pre- and postnatal overgrowth, organomegaly, macroglossia, omphalocele, neonatal hypoglycemia, hemihypertrophy, increased tumour risk

Genome-wide uniparental diploidy

~2 %

Yes

<1 %

chromosomal aberrations

2-4 %

No

Up to 50 %

IH19/IGF2: IG DMR; KCNQ1OT1: TSS-DMR

hypermethylation

5-10 %

Yes

unclear

hypomethylation

40-50 %

25 %

Yes

<1 %

CDKN1C

point mutations

5 % (sporadic) 40–50 % (families)

No

Up to 50 %

Kagami-Ogata syndrome (KOS14; upd(14)pat syndrome)

unknown

608149

14q32:

upd(14)pat

65 %

in case of RT

IUGR, polyhydramnion, abdominal and thoracal wall defects, bell-shaped thorax, coat-hanger ribs

MEG3/DLK1: IG DMR

maternal deletion

15 %

up to 50 %

MEG3: TSS DMR

aberrant methylation

20 %

<1 %

Temple syndrome (TS14; upd(14)mat syndrome)

unknown

616222

14q32:

upd(14)mat

78 %

In case of RT

IUGR/PNGR, neonatal hypotonia, feeding difficulties in infancy, truncal obesity, scoliosis, precocious puberty, small feed and hands

MEG3/DLK1: IG DMR

paternal deletion

10 %

Up to 50 %

MEG3: TSS DMR

aberrant methylation

12 %

1 case^a

<1 %

Prader-Willi syndrome (PWS)

1/25.000-1/10.000

176270

15q11-q13

paternal deletion

70 %

Up to 50 %

PNGR, mental retardation, neonatal hypotonia, hypogenitalism, hypopigmentation, obesity/hyperphagia

upd(15)mat

<30 %

In case of RT

aberrant methylation

~1 %

1 case

<1 %

Angelman syndrome (AS)

1/20.000-1/12.000

105830

15q11-q13:

maternal deletion

70 %

No

Up to 50 %

mental retardation, microcephaly, no speech, unmotivated laughing, ataxia, seizures, scoliosis

upd(15)pat

1-3 %

In case of RT

aberrant methylation

~4 %

Yes

<1 %

UBE3A

point mutations

10-15 %

No

In familial cases: up to 50 % in case of maternal transmission

Precocious puberty (central precocious puberty 2; cppb2)

Unknown

614356

15q11.2: MKRN3

point mutations

100 %

No

In familial cases: up to 50 % in case of paternal transmission

Early activation of the hypothalamic-pituitary-gonadal axis results in gonadotropin-dependent precocious puberty

Upd(16)mat

Unknown

Chromosome 16

upd(16)mat, often associated with chromosomal aberrations

Yes

<1 %

IUGR (40-85 %); heterogeneous, but no specific or unique symptoms

Pseudohypo-parathyroidism (PHP1B, PHP1C, PHP1A)

unknown

603233

20q13:

Maternally inherited deletions causing aberrant methylation

8.5 %

Up to 50 % in case of maternal transmission

Resistance to PTH and other hormones; Albright hereditary osteodystrophy, subcutaneous ossifications, feeding behaviour anomalies, abnormal growth patterns

612462

GNAS

isolated epimutations

42.5 %

12.5 %

<1 %

103580

upd(20)pat

2.5 %

12.5 %

<1 %

maternal and paternal heterozygous loss of function mutations in GNAS coding sequence

46.5 %

No

Up to 50 % in case of maternal transmission

Upd(20)mat syndrome

unknown

Chromosome 20

upd(20)mat

No

<1 %

IUGR, PNGR, feeding difficulties