Table 2 Overview of the main genetic syndromes that can present with neonatal hypoglycemia
Genetic Syndrome | Inheritance | Prevalence | Gene/Locus | Phenotype | Potential causes of HG | Incidence of HG |
|---|---|---|---|---|---|---|
Beckwith-Wiedemann | AD | 1:10,500-13,700 | UPD 11p15 | Macrosomia, macroglossia, hemihyperplasia, omphalocele, embryonal tumors, visceromegaly, adrenocortical cytomegaly, renal abnormalities, ear creases/pits | Hyperinsulinism | 30-50% |
CHARGE | AD | 1:10,000-15,000 | CHD7 8q12.2 | Coloboma of the eye, heart defects, choanal atresia, growth retardation, genito-urinary and ear anomalies | Hyperinsulinism; GHD; feeding difficulties; CAI | n.a |
Costello | AD | 1:300,000-1:1.25M | HRAS 11p15.5 | Coarse facial features (full lips, large mouth, full nasal tip); curly or sparse, fine hair; deep palmar and plantar creases; papillomata of the face and perianal region; ulnar deviation of the wrists and fingers; cardiac involvement | Hyperinsulinism; GHD; adrenal insufficiency | 44% |
Donohue | AR | <1:1M | INSR 19p13 | Small, elfin-like face, protuberant ears, distended abdomen, acromegaly, hypertrichosis, acanthosis nigricans, decreased subcutaneous fat | Accelerated fasting state due to insulin resistance | n.a |
Kabuki | KS1:AD KS2: XLR | 1:32,000-1:86,000 | KS1: KMT2D 12q13 KS2: KDM6A Xp11.3 | Eversion of the lower lateral eyelid, depressed nasal tip, arched eyebrows, prominent ears; skeletal anomalies, abnormal dermatoglyphic presentation | Hyperinsulinism; GHD; CAI | 6-8%, more common in KS2 |
Laron | AR | 1-9:1M | GHR 5p13-12 | Clinical hyposomatotropism, sparse hair, protruding and high forehead, shallow orbits, hypoplastic nasal bridge, small chin, hip degeneration | Resistance to GH counterregulatory activities | 33-42% |
Perlman | AR | <1:1M | DIS3L2 2q37.1 | Hypotonia, inverted V-shaped upper lip, prominent forehead, deep-set eyes, broad and flat nasal bridge, low-set ears, renal anomalies | Hyperinsulinism due to Langerhans islets’ hypertrophy | n.a |
Prader-Willi | AD | 1:25,000 | UDP 15q11–q13 | Diminished fetal activity, obesity, muscular hypotonia, mental retardation, short stature, hypogonadotropic hypogonadism, small hands and feet | Adrenal insufficiency; GHD | 12% |
Rabson-Mendenhall | AR | n.a | INSR 19p13 | Milder form of DS, hypertrichosis, acanthosis nigricans, prominent nipples, genital enlargement | Hyperinsulinism | n.a |
Silver Russell | AD | 1:30,000-1:100,000 | SRS1: ICR1 11p15.5 SRS2: UPD cr. 7 SRS3: IGF2 11p15 SRS4: PLAG1 8q12 SRS5: HMGA2 12q14 | Relative macrocephaly, triangular face, small lower jaw, low-set ears, frontal bossing, body asymmetry | Feeding difficulties; GHD; disproportionately large brain mass | 27%-60% |
Simpson-Golabi-Behmel | XLR | n.a | SGBS1: GPC3 Xq26 SGBS2: OFD1 Xp22 | Coarse facies, large protruding jaw, widened nasal bridge, upturned nasal tip, enlarged tongue, congenital heart defects | Hyperinsulinism | n.a |
Sotos | SoS1/2: AD SoS 3: AR | 1:10,000-1:14,000 | SoS1: NSD1 5q35 SoS2: NFIX 19p13 SoS3: APC2 19p13 | Macrocephaly, dolichocephaly, broad and prominent forehead, sparse frontotemporal hair, downslanting palpebral fissures, long and narrow face | Hyperinsulinism | 2-15% |
Timothy | AD | <1:1M | CACNA1C 12p13 | Hypotonia, round face, depressed nasal bridge, low-set ears, thin vermilion of the upper lip, hypoplastic premaxillary cutaneous syndactyly, congenital hip abnormalities, congenital heart disease, long QT syndrome | Hyperinsulinism due to altered influx of Ca2+ into pancreatic β-cells which triggers insulin secretion | 36% |
Turner | Sporadic | 1-5:10,000 (1:2,500 F) | 45, X0 | Webbed neck, low hairline at the back of the neck, low-set ears, small mandible, lymphedema of extremities, multiple pigmented nevi | Hyperinsulinism due to increased sensitivity of pancreatic islets to aminoacids and elevated basal cytosolic calcium, possibly caused by haploinsufficiency of KDM6A (disruption of epigenetic changes during pancreatic differentiation); GHD | Rare |