The vast majority of cases are thought to be due to spontaneous genetic mutations. It can be associated with mutations affecting the cohesin complex. As of 2018, it was confirmed that 500 genetic mutations have been associated with the condition; occurring on 7 different genes. In around 30% of cases of<unk>  the genetic cause remains undiscovered. The wide variation in phenotype is attributed to a high<unk> gree of somatic mosaicism in<unk>  as well as the different genes and type of mutations. For this reason people with<unk>  can have very different appearance, abilities, and associated health issues. Name OMIM Gene Appx. % Notes<unk> 1 NIPBL 50% A gene responsible for<unk>  on chromosome 5 was discovered in 2004 jointly by researchers at the Children's Hospital of Philadelphia, USA and researchers at Newcastle University, UK.<unk> 2 SMC1A 5% In 2006, a second gene, on the X chromosome, was found by Italian scientists.<unk> 3 SMC3 1% A third gene discovery was announced in 2007. The gene is on chromosome 10 and was also discovered by the research team in Philadelphia. The latter two genes seem to correlate with a milder form of the syndrome. In 2004, researchers at the Children's Hospital of Philadelphia (United States) and the University of Newcastle upon Tyne (England) identified a gene (NIPBL) on chromosome 5 that causes<unk>  when it is mutated. Since then, additional genes have been found (SMC1A, SMC3 and HDAC8, RAD21) that cause<unk>  when changed. In July 2012, the fourth "CdLS gene"—HDAC8—was announced. HDAC8 is an X-linked gene, meaning it is located on the X chromosome. Individuals with<unk>  who have the gene change in HDAC8 make up just a small portion of all people with<unk> . Evidence of a linkage at chromosome 3q26.3 is mixed. Genetic alterations associated with<unk>  have been identified in genes NIPBL, SMC1A and SMC3 as well as the more recently identified genes RAD21 and HDAC8. All of these genetic alterations occurring in<unk>  patients affect proteins that function in the cohesin pathway. SMC1A, SMC3 and RAD21 proteins are structural components of the cohesin ring complex. NIPBL is involved in the loading of the cohesin ring onto chromosomes, and HDAC8<unk> acylates SMC3 to facilitate its function. The cohesin pathway is involved in cohesion of sister chromatids during mitosis, DNA repair, chromosome segregation and the regulation of<unk> velopmental gene expression.<unk> fects in these functions are theorised to underlie some of the features of<unk> . In particular,<unk> fective DNA repair may underlie the features of premature aging.
Cornelia de Lange syndrome
Lesch–Nyhan syndrome
Axenfeld–Rieger syndrome
Kufor–Rakeb syndrome
Foster Kennedy syndrome
Pelizaeus–Merzbacher disease
Joubert syndrome
TORCH syndrome