## 6 Determinant Factors of Obesity
### Obesity as a Symptom
#### 6.2.1 Genetic Syndromes  
Several genetic syndromes intervene in obesogenic mechanisms and lead to weight excess [179].  
Prader-Willi syndrome (PWS) is one such example, where an anomaly involving the partial disappearance of oxytocin neurons [180] within the hypothalamus leads to the impossibility of achieving satiety. The resulting hyperplasia leads to severe obesity, which in turn leads to limitation of physical activity and corresponding energy expenditure, thus intensifying weight gain and leading to loss of muscle mass. Obesity in Prader-Willi syndrome commonly has a central predisposition (abdomen, hips, thighs) in both genders and is usually the main causative factor behind morbidity and mortality associated with this disease. The current literature reports higher levels for orexigenic hormone (ghrelin) in PWS children than in other obese children. In PWS, children starting with nutritional phase 3 (8 years of age) ghrelin levels increase before the meal but also after the meal, pointing to a hypothalamic pathway dysfunction related to appetite regulation [181].  
[PERSON] syndrome is associated with a prevalence of obesity of 72-86%. Children with [PERSON] syndrome are typically born with a normal weight, a third of which will however develop weight excess by the age of 1. Individuals with [PERSON] syndrome are prone to developing diabetes mellitus, hypertension, and metabolic syndrome [182; 183].  
[PERSON] syndrome is a rare genetic disease that frequently associates obesity involving the proximal regions of the limbs, the face, neck, and thorax [184]. It is an acrocephaloly syndactly type II associating craniosynostosis, learning disability, cardiac defects, obesity, and polysynodactyl. A mutation in the gene RAB23 gene leads to subsequent RAS dysfunction and impaired intracellular vascular transport. The encoded GTPase is a negative regulator for hedgehog (HH) family signaling; however, it is not yet clear how these pathways can be linked with obesity. It is known that HH signaling inhibits adipose tissue hypertrophy and hyperplasia [185].  
Cohen syndrome (CS) is a recessive autosomal disease defined by the presence of multiple congenital malformations and intellectual disability. In this disease, obesity predominantly affects the torso and has a characteristic disposition, characterized as \"truncal obesity\". CS was described in the Finnish population and is due to mutations in a vacuolar protein sorting 13 homolog B(VPS13B) gene. This protein is necessary to the Golgi network and endosomal transport [186; 187].  
**Alstrom syndrome** is a recessive autosomal disease involving the mutation of ALMS1, defined by the presence of obesity, type 2 diabetes, and neurosensory degeneration [188]. Recent data presents ALMS as a ciliopathy due to mutation in the ALMS1 gene (located in the centromeres) along with another ciliopathy, Bardet-Biedl syndrome, which is polygenic. However, in ALMS patients, obesity is more severe and ensues in the first years of life (until the age of 5). ALMS gene has its location in the centrosomes and is involved in the microtubules' functions. It has important roles in both visual and auditory analyzers, lungs, heart, liver, and kidneys' function and, most importantly, in metabolic regulation. It seemsthat not only the subcutaneous adipose tissues' function is severely deregulated, but also the skeletal and hepatic ones with subsequent insulin resistance. These patients have large dysfunctional adipocytes [189].