Table 1.

Molecular basis of imprinting disorders.

Imprinting disorder [OMIM]	Chromosome/Imprinted gene	Molecular defects	Key clinical features	Current treatment
Diabetes mellitus, transient neonatal,1 [601410]	6q24/PLAGL1, HYMAI	UPD (chr6) pat, paternal duplications, methylation defects on PLAGL1 TSS (caused by mutation in ZFP57 gene at chr6p22)	Intrauterine growth retardation, neonatal diabetes mellitus, hyperglycemia, macroglossia	Insulin
Silver-Russell syndrome 1 [180860] 2 [618905] 3 [616489]	11p15.5/H19, IGF2 7p13-q32/C7ORF10 11p15.5/IGF2	UPD (chr11p15) mat, chr11p15 CNVs, UPD (chr7) mat, methylation defects on H19 and IGF2 genes	Pre- and postnatal growth deficiency, asymmetry, broad forehead, facial dysmorphism, macrocephaly, gastrointestinal symptoms	Growth hormone
Birk–Barel syndrome [612292]	8q24.3/KCNK9	KCNK9 missense mutation on maternal gene	Developmental delay, central hypotonia, facial dysmorphism, intellectual disability,	Symptomatic care
Beckwith–Wiedemann syndrome [130650]	11p15.5/H19, IGF2	UPD (chr11p15) pat, hypermethylation on H19 and IGF2 genes imprinting control region (ICR1)	Hypoglycemia, hyperinsulinism, Macroglossia, overgrowth, abdominal abnormalities	Surgery to treat cases with omphalocele or umbilical hernia
Kagami–Ogata syndrome [608149]	14q32/ DLK1,MEG3, RTL1, MEG8, miRNAs, SNORDs, DIO3, RTL1as	UPD (chr14) pat, 14q32 mat deletion, hypermethylation on MEG3–DLK1 region	Polyhydramnios, macrosomia, placentomegaly, hypotonia, developmental delay, abdominal wall defects, cardiac/thoracic abnormalities	Growth hormone
Temple syndrome [616222]	14q32/ DLK1,MEG3, RTL1, MEG8, miRNAs, SNORDs, DIO3, RTL1as	UPD (chr14) mat, 14q32 pat deletion, hypomethylation on MEG3–DLK1 region	Postnatal short stature, hypotonia, developmental delay, small hands and feet, intellectual disability	Growth hormone
Prader–Willi syndrome [176270]	15q11.2-q13/MRKN3, MAGEL2, NDN, PWRN4, PWRN3, SNURF-SNRPN, SNORDs IPW	chr15q11.2-q13 pat deletion, UPD (chr13) mat, imprinting defect, deletion of paternal SNORD116	Hypotonia, developmental delay, intellectual disability, hyperphagia, hypogonadism, diabetes type II	Growth hormone
Angelman syndrome [105830]	15q11.2-q13/UBE3A	chr15q11.2-q13 mat deletion, UPD (chr13) pat, imprinting defect, UBE3A point mutation on maternal allele	Unmotivated laughing, ataxia, microcephaly, developmental delay, seizures, hyperreflexia	Anti-epileptic drug
Central precocious puberty 2 [615356]	15q11.2/MKRN3	MKRN3 point mutations on the paternal allele	Gonadotropin-dependent precocious puberty	GnRH analog therapy
Schaaf–Yang syndrome [615547]	15q11.2/MAGEL2	MAGEL2 point mutations on the paternal allele	Psychomotor developmental delay, hypotonia, behavioral abnormalities, intellectual disability	Growth hormone, anti-psychotic medication, non-invasive ventilation
Pseudohypopara-thyroidism1A (PHP1A) [103580] / PHP1C [612462]	20q13.32/GNAS	Inactivating mutation on maternal allele of GNAS	Albright hereditary osteodystrophy, resistance to parathyroid / other hormones, obesity, cognitive impairment	Growth hormone, Vitamin D
Pseudohypopara-thyroidism1B (PHP1B) [603233]	20q13.32/STX16, GNASAS1, GNAS	Imprinting defect on maternal allele of GNAS, 20q13 mat deletion, UPD (chr20) pat	Albright hereditary osteodystrophy, resistance to parathyroid / other hormones, cognitive impairment	Calcium, Vitamin D
Pseudopseudohypo-parathyroidism (PPHP) [612463]	20q13.32/GNAS	Inactivating mutation on paternal allele of GNAS	Albright hereditary osteodystrophy, mental retardation	Calcium, Vitamin D
Progressive osseous heteroplasia [166350]	20q13.32/GNAS	Inactivating mutation on paternal allele of GNAS	Heterotopic ossification	Bis-phosphonate pamidronate
Mulchandani–Bhoj–Conlin syndrome [617352]	20q11-q13/GNAS	UPD (chr20) mat	Prenatal growth restriction, severe short stature, proportional head circumference, profound feeding difficulty	Growth hormone