CHOPS syndrome
CHOPS syndrome is an extremely rare congenital disorder characterized by cognitive impairment, coarse facial features, heart defects, obesity, pulmonary involvement, short stature, and skeletal abnormalities.
Overview
CHOPS syndrome is a disorder involving multiple abnormalities that are present from birth (congenital). The name "CHOPS" is an acronym that represents the primary features of the disorder: cognitive impairment, coarse facial features, heart defects, obesity, lung (pulmonary) involvement, short stature, and skeletal abnormalities.
Symptoms & Characteristics
Children with CHOPS syndrome experience a wide range of developmental, physical, and medical challenges:
- Cognitive & Developmental Delay: Affected children have intellectual disability and delayed development of motor skills, such as sitting and walking.
- Coarse Facial Features: Characteristic facial features include a round face; thick hair; thick eyebrows that grow together in the middle (synophrys); wide-set, bulging eyes with long eyelashes; a short nose; and down-turned corners of the mouth.
- Heart Defects: Most affected individuals are born with patent ductus arteriosus (PDA), a condition where the connection between the aorta and the pulmonary artery remains open after birth. If untreated, PDA can cause rapid breathing, poor feeding, slow weight gain, and potentially heart failure. Other heart abnormalities, such as a ventricular septal defect (VSD)—a defect in the muscular wall separating the lower chambers of the heart—may also occur.
- Pulmonary Involvement: Abnormalities of the throat and airways cause obstructive sleep apnea (momentary cessation of breathing during sleep). These abnormalities can also cause affected individuals to accidentally breathe food or fluids into the lungs, potentially leading to life-threatening bacterial lung infections (aspiration pneumonia) and chronic lung disease.
- Short Stature & Obesity: Affected individuals are shorter than more than 97 percent of their peers and are overweight for their height.
- Skeletal Abnormalities: Skeletal differences include unusually short fingers and toes (brachydactyly) and abnormally-shaped spinal bones (vertebrae).
- Other Features: Additional signs can include a small head size (microcephaly), hearing loss, clouding of the lens of the eye (cataract), a single, horseshoe-shaped kidney, and undescended testes (cryptorchidism) in affected males.
Frequency
CHOPS syndrome is an extremely rare disorder. Its exact prevalence is unknown, and only a few affected individuals have been described in the medical literature.
Causes
CHOPS syndrome is caused by mutations in the AFF4 gene. This gene provides instructions for making part of a protein complex called the super elongation complex (SEC). During embryonic development, the SEC is involved in transcription, which is the first step in the production of proteins from genes. By re-starting the transcription of certain genes after pauses that normally occur during the process, the SEC helps ensure that development proceeds appropriately before birth.
Mutations in the AFF4 gene are thought to result in an AFF4 protein that is not broken down when it is no longer needed, leading to an excess of the protein. This excess AFF4 protein interferes with normal pauses in transcription. This dysregulation of transcription leads to problems in the development of multiple organs and tissues, resulting in the signs and symptoms of CHOPS syndrome.
Associated Gene
- AFF4
Inheritance
CHOPS syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. All known cases of this condition result from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) or in early embryonic development. Affected individuals have no history of the disorder in their family.
Other Names for This Condition
- Cognitive impairment, coarse facies, heart defects, obesity, pulmonary involvement, short stature, and skeletal dysplasia