IllnessAdipositas, severe, pure, early onset; differential diagnosis

NGS +

Obesity is usually multifactorial. In rare cases it is caused by mutations in one of the genes involved in controlling hunger and satiety. This is usually early onset obesity (EOO; BMI increased by two or more standard deviations at the age of 5 years). The most common of the individual gene alterations affect the MC4R gene more rarely the leptin receptor gene (LEPR) and the LEP gene resulting in a congenital leptin deficiency, which manifests itself as intense hyperphagia, EOO and severe obesity in conjunction with hormonal and metabolic changes. The inheritance is autosomal recessive, the penetrance is not known in only a few more than100 mutation carriers.

Reference: https://www.nature.com/articles/s41576-021-00414-z

• Allelic: ACTH-independent macronodular adrenal hyperplasia (GNAS)
• Allelic: Epileptic encephalopathy, early infantile, 58 (NTRK2)
• Allelic: McCune-Albright syndrome, somatic, mosaic (GNAS)
• Allelic: Mental retardation, AD 39 (MYT1L)
• Allelic: Osseous heteroplasia, progressive (GNAS)
• Allelic: Pituitary adenoma 3, multiple types, somatic (GNAS)
• Allelic: Pseudohypoparathyroidism Ia (GNAS)
• Allelic: Pseudohypoparathyroidism Ib (GNAS)
• Allelic: Pseudohypoparathyroidism Ic (GNAS)
• Allelic: Pseudopseudohypoparathyroidism (GNAS)
• Abdominal obesity-metabolic syndrome 3 (DYRK1B)
• BDV syndrome - Blakemore-Durmaz-Vasileiou syndrome (CPE)
• Borjeson-Forssman-Lehmann syndrome (PHF6)
• Chung-Jansen syndrome: developm. delay, impaired ID/learning, behavior, dysmorphism, obesity (PHIP)
• Cohen syndrome (VPS13B)
• Congenital obesity [panelapp] (SIM1)
• Joubert syndrome 1 (INPP5E)
• Mental retardation, truncal obesity, retinal dystrophy + micropenis (INPP5E)
• Morbid obesity + spermatogenic failure (CEP19)
• Neurodevelopmental disorder [panelapp] (PGM2L1)
• Obesity [panelapp] (KSR2)
• Obesity with impaired prohormone processing (PCSK1)
• Obesity, BMIQ20 (MC4R)
• Obesity, adrenal insufficiency, red hair due to POMC deficiency (POMC)
• Obesity, congenital (GNAS)
• Obesity, early-onset, susceptibility to (POMC)
• Obesity, hyperphagia + developmental delay (NTRK2)
• Obesity, mental retardation, AD 39 (MYT1L)
• Obesity, morbid, due to leptin deficiency (LEP)
• Obesity, morbid, due to leptin receptor deficiency (LEPR)
• Obesity, resistance to; BMIQ20 (MC4R)
• Obesity, severe (SIM1)
• Obesity, severe, susceptibility to, BMIQ9 (MC3R)
• Obesity, susceptibility to, BMIQ12 (PCSK1)
• Obesity, susceptibility to, BMIQ18 (MRAP2)
• Obesity, susceptibility to, BMIQ19 (ADCY3)
• Obesity, susceptibility to, BMIQ4 (UCP2)
• Retinal dystrophy + obesity (TUB)
• Severe early-onset obesity-insulin resistance syndrome due to SH2B1 defic. [MONDO:0017994] (SH2B1)
• Truncal obesity developing in mid-childhood (VPS13B)
• WAGRO s. [Wilms tumor, Aniridia, Genitourin. anom., ment. Retard., Obes.] (11p13-p12/BDNF deletion)