In all Caucasian populations, this particular mutation has an estimated carrier frequency of 3%.The next most common mutation is 278C>T, and results in a threonine at the amino acid position 93. It is a missense mutation and tends to be associated with less severe symptoms. This mutation is the most common one seen in patients of Italian, Cuban, and Mediterranean descent.The third most common mutation is  452G>A. This nonsense mutation causes protein termination, such that the enzyme DHCR7 would not be formed. It is thought to have arisen in Southern Poland and is most common in Northern Europe.Other mutations are less common, although appear to target certain protein domains more so than others. For example, the sterol reductase motifs are common sites of mutation. Overall, there is an estimated carrier frequency (for any DHCR7 mutation causing SLOS) of 3-4% in Caucasian populations (it is less frequent among Asian and African populations). This number indicates a hypothetical birth incidence between 1/2500 and 1/4500. However, the measured incidence is between 1/10,000 to 1/60,000 (it differs depending on heritage and descent). This is much lower than expected. This indicates that many cases of SLOS are undetected, and is likely due to either spontaneous abortion caused by severe mutations (miscarriage), or mild cases that are undiagnosed. Females lack the characteristic genital malformations that affected males have, and thus are less likely to be correctly diagnosed. Cholesterol metabolism and function
Metabolism
Cholesterol can be obtained through the diet, but it can also be formed by metabolism in the body.
Synucleinopathies (also called α-Synucleinopathies) are neurodegenerative diseases characterised by the abnormal accumulation of aggregates of alpha-synuclein protein in neurons, nerve fibres or glial cells. There are three main types of synucleinopathy: Parkinsons disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Other rare disorders, such as various neuroaxonal dystrophies, also have α-synuclein pathologies. Additionally, autopsy studies have shown that around 6% of sporadic Alzheimers Disease exhibit α-synuclein positive Lewy pathology, and are sub-classed as Alzheimers Disease with Amygdalar Restricted Lewy Bodies (AD/ALB). Presentation
The synucleinopathies have shared features of parkinsonism, impaired cognition, sleep disorders, and visual hallucinations.Synucleinopathies can sometimes overlap with tauopathies, possibly because of interaction between the synuclein and tau proteins.REM sleep behavior disorder (RBD) is a parasomnia in which individuals with RBD lose the paralysis of muscles (atonia) that is normal during rapid eye movement (REM) sleep, and act out their dreams or have other abnormal movements or vocalizations. Abnormal sleep behaviors may appear decades before any other symptoms, often as an early sign of a synucleinopathy. On autopsy, 94 to 98% of individuals with polysomnography-confirmed RBD are found to have a synucleinopathy—most commonly DLB or PD. Other symptoms of the specific synucleinopathy usually manifest within 15 years of the diagnosis of RBD, but may emerge up to 50 years after RBD diagnosis.Alpha-synuclein deposits can affect the cardiac muscle and blood vessels. Almost all people with synucleinopathies have cardiovascular dysfunction, although most are asymptomatic.From chewing to defecation, alpha-synuclein deposits affect every level of gastrointestinal function.