Imprinting disorders and methylation disturbances in short children born SGA
| Syndrome [OMIM] . | Epigenetic defect . | Incidence . | Mean BW/BL SDS . | Clinical features besides SGA . | Treatment . |
|---|---|---|---|---|---|
| Silver-Russell syndrome [180860] | 11p15 LOM (30%-60%), upd(7)mat (5-10%), upd(20)mat, upd(16)mat act CDKN1C, HMAG2, PLAG1 and CNVs Exception # Paternal IGF2 mutation (see Table 1) | 1:30,000-100,000 | 11p15:−3.2/−4.5 UPD7:−2.3/−2.5 Clinical: −2.7/−1.8 | Relative macrocephaly, protruding forehead, body asymmetry, feeding problems and/or low BMI | GH effective (in label of registered GH treatment for short SGA) |
| Temple syndrome [616222] | 14q32 abnormalities: upd(14)mat, paternal microdeletions, hypomethylation of DLK1/GTL2 IG-DMR | < 100 cases | −1.9/−1.6 | Postnatal growth failure, hypotonia, delayed development of motor skills, feeding problems in infancy, early puberty, broad forehead, short nose with wide nasal tip, small hands and feet | Insufficient data |
| IMAGe syndrome [614732] | Maternally inherited activating mutations in CDKN1C | ≈ 15 cases | −2.0 to −4.0 | Relative macrocephaly at birth, no or mild intellectual disability, frontal bossing, low-set ears, flat nasal bridge, short nose, congenital adrenal hypoplasia, metaphyseal and/or epiphyseal dysplasia, male genital anomalies, early-onset type 1 DM | Insufficient data |
| Prader-Willi syndrome [176270] | Paternal 15q11.2q13 deletion (60%), upd(15)mat (40%), or imprinting center mutation (1-3%). Loss of SNRPN and NDN expression | 1:16.000 | −1.2/−1.1 | Diminished fetal activity, obesity, muscular hypotonia, intellectual disability, short stature, hypogonadotropic hypogonadism, small hands and feet | GH registered for PWS |
| Pseudohypopara-thyroidism type 1a/ca [103580] | Heterozygous GNAS1 mutation inherited from the mother | 1:150.000 | −0.6/−1.1 35% born SGA | Resistance to PTH and other hormones (TSH, LH, FSH and GHRH), Albright hereditary osteodystrophy (short stature, obesity, round face, subcutaneous ossifications, brachydactyly, mild intellectual disability) | Insufficient data |
| Pseudopseudo-hypoparathyroi-dism [612463]) | Heterozygous GNAS1 mutation inherited from the father | 1:150.000 | −2.7/−3.0 95% born SGA | Albright hereditary osteodystrophy without multiple hormone resistance and no hypocalcemia | Insufficient data |
| Syndrome [OMIM] . | Epigenetic defect . | Incidence . | Mean BW/BL SDS . | Clinical features besides SGA . | Treatment . |
|---|---|---|---|---|---|
| Silver-Russell syndrome [180860] | 11p15 LOM (30%-60%), upd(7)mat (5-10%), upd(20)mat, upd(16)mat act CDKN1C, HMAG2, PLAG1 and CNVs Exception # Paternal IGF2 mutation (see Table 1) | 1:30,000-100,000 | 11p15:−3.2/−4.5 UPD7:−2.3/−2.5 Clinical: −2.7/−1.8 | Relative macrocephaly, protruding forehead, body asymmetry, feeding problems and/or low BMI | GH effective (in label of registered GH treatment for short SGA) |
| Temple syndrome [616222] | 14q32 abnormalities: upd(14)mat, paternal microdeletions, hypomethylation of DLK1/GTL2 IG-DMR | < 100 cases | −1.9/−1.6 | Postnatal growth failure, hypotonia, delayed development of motor skills, feeding problems in infancy, early puberty, broad forehead, short nose with wide nasal tip, small hands and feet | Insufficient data |
| IMAGe syndrome [614732] | Maternally inherited activating mutations in CDKN1C | ≈ 15 cases | −2.0 to −4.0 | Relative macrocephaly at birth, no or mild intellectual disability, frontal bossing, low-set ears, flat nasal bridge, short nose, congenital adrenal hypoplasia, metaphyseal and/or epiphyseal dysplasia, male genital anomalies, early-onset type 1 DM | Insufficient data |
| Prader-Willi syndrome [176270] | Paternal 15q11.2q13 deletion (60%), upd(15)mat (40%), or imprinting center mutation (1-3%). Loss of SNRPN and NDN expression | 1:16.000 | −1.2/−1.1 | Diminished fetal activity, obesity, muscular hypotonia, intellectual disability, short stature, hypogonadotropic hypogonadism, small hands and feet | GH registered for PWS |
| Pseudohypopara-thyroidism type 1a/ca [103580] | Heterozygous GNAS1 mutation inherited from the mother | 1:150.000 | −0.6/−1.1 35% born SGA | Resistance to PTH and other hormones (TSH, LH, FSH and GHRH), Albright hereditary osteodystrophy (short stature, obesity, round face, subcutaneous ossifications, brachydactyly, mild intellectual disability) | Insufficient data |
| Pseudopseudo-hypoparathyroi-dism [612463]) | Heterozygous GNAS1 mutation inherited from the father | 1:150.000 | −2.7/−3.0 95% born SGA | Albright hereditary osteodystrophy without multiple hormone resistance and no hypocalcemia | Insufficient data |
Abbreviations: act, activating; BL, birth length; BMI, body mass index; BW, birth weight; DM, diabetes mellitus; FSH, follicle-stimulating hormone; LH, luteinizing hormone; LOM, loss of methylation; SGA, small for gestational age; upd()mat, maternal uniparental disomy.
Pseudohypoparathyroidism type 1b [OMIM 603233] is associated with normal or increased birth weight and overgrowth in childhood.
Imprinting disorders and methylation disturbances in short children born SGA
| Syndrome [OMIM] . | Epigenetic defect . | Incidence . | Mean BW/BL SDS . | Clinical features besides SGA . | Treatment . |
|---|---|---|---|---|---|
| Silver-Russell syndrome [180860] | 11p15 LOM (30%-60%), upd(7)mat (5-10%), upd(20)mat, upd(16)mat act CDKN1C, HMAG2, PLAG1 and CNVs Exception # Paternal IGF2 mutation (see Table 1) | 1:30,000-100,000 | 11p15:−3.2/−4.5 UPD7:−2.3/−2.5 Clinical: −2.7/−1.8 | Relative macrocephaly, protruding forehead, body asymmetry, feeding problems and/or low BMI | GH effective (in label of registered GH treatment for short SGA) |
| Temple syndrome [616222] | 14q32 abnormalities: upd(14)mat, paternal microdeletions, hypomethylation of DLK1/GTL2 IG-DMR | < 100 cases | −1.9/−1.6 | Postnatal growth failure, hypotonia, delayed development of motor skills, feeding problems in infancy, early puberty, broad forehead, short nose with wide nasal tip, small hands and feet | Insufficient data |
| IMAGe syndrome [614732] | Maternally inherited activating mutations in CDKN1C | ≈ 15 cases | −2.0 to −4.0 | Relative macrocephaly at birth, no or mild intellectual disability, frontal bossing, low-set ears, flat nasal bridge, short nose, congenital adrenal hypoplasia, metaphyseal and/or epiphyseal dysplasia, male genital anomalies, early-onset type 1 DM | Insufficient data |
| Prader-Willi syndrome [176270] | Paternal 15q11.2q13 deletion (60%), upd(15)mat (40%), or imprinting center mutation (1-3%). Loss of SNRPN and NDN expression | 1:16.000 | −1.2/−1.1 | Diminished fetal activity, obesity, muscular hypotonia, intellectual disability, short stature, hypogonadotropic hypogonadism, small hands and feet | GH registered for PWS |
| Pseudohypopara-thyroidism type 1a/ca [103580] | Heterozygous GNAS1 mutation inherited from the mother | 1:150.000 | −0.6/−1.1 35% born SGA | Resistance to PTH and other hormones (TSH, LH, FSH and GHRH), Albright hereditary osteodystrophy (short stature, obesity, round face, subcutaneous ossifications, brachydactyly, mild intellectual disability) | Insufficient data |
| Pseudopseudo-hypoparathyroi-dism [612463]) | Heterozygous GNAS1 mutation inherited from the father | 1:150.000 | −2.7/−3.0 95% born SGA | Albright hereditary osteodystrophy without multiple hormone resistance and no hypocalcemia | Insufficient data |
| Syndrome [OMIM] . | Epigenetic defect . | Incidence . | Mean BW/BL SDS . | Clinical features besides SGA . | Treatment . |
|---|---|---|---|---|---|
| Silver-Russell syndrome [180860] | 11p15 LOM (30%-60%), upd(7)mat (5-10%), upd(20)mat, upd(16)mat act CDKN1C, HMAG2, PLAG1 and CNVs Exception # Paternal IGF2 mutation (see Table 1) | 1:30,000-100,000 | 11p15:−3.2/−4.5 UPD7:−2.3/−2.5 Clinical: −2.7/−1.8 | Relative macrocephaly, protruding forehead, body asymmetry, feeding problems and/or low BMI | GH effective (in label of registered GH treatment for short SGA) |
| Temple syndrome [616222] | 14q32 abnormalities: upd(14)mat, paternal microdeletions, hypomethylation of DLK1/GTL2 IG-DMR | < 100 cases | −1.9/−1.6 | Postnatal growth failure, hypotonia, delayed development of motor skills, feeding problems in infancy, early puberty, broad forehead, short nose with wide nasal tip, small hands and feet | Insufficient data |
| IMAGe syndrome [614732] | Maternally inherited activating mutations in CDKN1C | ≈ 15 cases | −2.0 to −4.0 | Relative macrocephaly at birth, no or mild intellectual disability, frontal bossing, low-set ears, flat nasal bridge, short nose, congenital adrenal hypoplasia, metaphyseal and/or epiphyseal dysplasia, male genital anomalies, early-onset type 1 DM | Insufficient data |
| Prader-Willi syndrome [176270] | Paternal 15q11.2q13 deletion (60%), upd(15)mat (40%), or imprinting center mutation (1-3%). Loss of SNRPN and NDN expression | 1:16.000 | −1.2/−1.1 | Diminished fetal activity, obesity, muscular hypotonia, intellectual disability, short stature, hypogonadotropic hypogonadism, small hands and feet | GH registered for PWS |
| Pseudohypopara-thyroidism type 1a/ca [103580] | Heterozygous GNAS1 mutation inherited from the mother | 1:150.000 | −0.6/−1.1 35% born SGA | Resistance to PTH and other hormones (TSH, LH, FSH and GHRH), Albright hereditary osteodystrophy (short stature, obesity, round face, subcutaneous ossifications, brachydactyly, mild intellectual disability) | Insufficient data |
| Pseudopseudo-hypoparathyroi-dism [612463]) | Heterozygous GNAS1 mutation inherited from the father | 1:150.000 | −2.7/−3.0 95% born SGA | Albright hereditary osteodystrophy without multiple hormone resistance and no hypocalcemia | Insufficient data |
Abbreviations: act, activating; BL, birth length; BMI, body mass index; BW, birth weight; DM, diabetes mellitus; FSH, follicle-stimulating hormone; LH, luteinizing hormone; LOM, loss of methylation; SGA, small for gestational age; upd()mat, maternal uniparental disomy.
Pseudohypoparathyroidism type 1b [OMIM 603233] is associated with normal or increased birth weight and overgrowth in childhood.
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