CHOPS Syndrome

What it is

CHOPS syndrome is an extremely rare genetic disease with a prevalence of less than 1 individual in 1,000,000. It is described in medical literature with only 13 cases.

CHOPS syndrome involves several abnormalities that are present from birth (ie congenital). The name CHOPS is the acronym of Cognitive impairment and Coarse facies, Heart defects, Obesity, Pulmonary involvement, Short stature and Skeletal dysplasia, or the list of the main characteristics of the syndrome.

Children with CHOPS syndrome have intellectual disabilities and slowed development of skills such as the ability to sit or walk. Many children with CHOPS are silent. Characteristic facial details include a round face, thick hair, thick eyebrows that come together in the center (synophry), eyes with long lashes, a short nose, and downturned corners of the mouth.

Most affected individuals are born with a heart defect known as a patent ductus arteriosus. The ductus arteriosus connects two main arteries, the pulmonary artery and the aorta. The duct is open during fetal development and normally closes immediately after birth. If not done and left untreated, it can cause rapid breathing, feeding difficulties and poor weight gain and, in severe cases, cardiac arrest. More than one abnormality has often been found in children with CHOPS syndrome. In addition to patent ductus arteriosus, multiple interventricular defect (or defects) is sometimes associated (VSD). This consists of an abnormal communication at the level of the interventricular septum, the wall that separates the two main cardiac chambers of the heart: the right and left ventricles.

Individuals with CHOPS have airway abnormalities that cause problems such as obstructive sleep apnea. These abnormalities can also lead to accidental inhalation of food or liquids, possibly resulting in bacterial lung infections (aspiration pneumonia) and chronic respiratory disease.

Children with CHOPS have short stature and are overweight. They also typically have skeletal anomalies such as brachydactyly and vertebral anomalies. In the CHOPS syndrome are also described, among others, ophthalmological problems (myopia, cataract, glaucoma…), genital anomalies and gastrointestinal disorders (gastroesophageal reflux, constipation…).

CHOPS syndrome is caused by mutations in the AFF4 gene. This gene provides instructions for building a protein complex known as a super elongation complex (SEC). During embryogenesis, the ECS is involved in a process called transcription, the first step in the production of proteins from genes. Mutations in the AFF4 gene are thought to cause accumulation of the AFF4 protein. The excess of the latter interferes with transcription, with consequent problems in the development of various organs and tissues, which give rise to the typical symptoms of CHOPS. The same mechanisms are involved in the cohesins, whose mutations are responsible for other syndromic conditions known as “cohesynopathies”, of which Cornelia de Lange syndrome is a part.

CHOPS syndrome is inherited in an autosomal dominant pattern, which means that one copy of the altered gene is sufficient to cause the disease. All cases known to date result from “de novo” mutations of the gene, ie they are of new onset in the affected individual. Also CHOPS individuals do not have a family history characterized by the same disorder.

Reference scientific bibliography

Raible SE, et al., Clinical and molecular spectrum of CHOPS syndrome. Am J Med Genet A. 2019 Jul;179(7):1126-1138. doi:10.1002/ajmg.a.61174. Epub 2019 May 6. PMID: 31058441; PMC ID: PMC7473581.

Izumi K, et al., Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin. Nat Genet. 2015 Apr;47(4):338-44. doi:10.1038/ng.3229. Epub 2015 Mar 2. PMID: 25730767; PMCID: PMC4380798.

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CHOPS Syndrome

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