NORD gratefully acknowledges Antonie Kline, MD, Medical Director, Cornelia de Lange Syndrome (CdLS) Foundation, Inc., Director of Pediatric Genetics, Harvey Institute of Human Genetics, Greater Baltimore Medical Center, for assistance in the preparation of this report.
Cornelia de Lange syndrome (CdLS) is a rare genetic disorder that is apparent at birth (congenital). Associated symptoms and findings typically include delays in physical development before and after birth (prenatal and postnatal growth retardation); characteristic abnormalities of the head and facial (craniofacial) area, resulting in a distinctive facial appearance; malformations of the hands and arms (upper limbs); and mild to severe intellectual disability. Many infants and children with the disorder have an unusually small, short head (microbrachycephaly); a prominent vertical groove between the upper lip and nose (philtrum); a depressed nasal bridge; upturned nostrils (anteverted nares); and a protruding upper jaw (maxillary prognathism) with small chin (micrognathia). Additional characteristic facial abnormalities may include thin, downturned lips; low-set ears; arched, well-defined eyebrows that grow together across the base of the nose (synophrys); an unusually low hairline on the forehead and the back of the neck; and curly, unusually long eyelashes. Affected individuals may also have distinctive malformations of the limbs, such as unusually small hands and feet, inward deviation (clinodactyly) of the fifth fingers, and webbing (syndactyly) of certain toes. Less commonly, there may be absence of the forearms, hands, and fingers. Infants with CdLS may also have feeding and breathing difficulties; an increased susceptibility to respiratory infections; a low-pitched "growling" cry and low voice; heart defects; delayed skeletal maturation; hearing loss; or other physical abnormalities. The range and severity of associated symptoms and findings may be extremely variable from person to person.
CdLS can be inherited as an autosomal dominant condition or an X-linked condition. Five genes have been found to be associated with CdLS including the NIPBL gene on chromosome 5, the SMC1A gene on the X chromosome, the SMC3 gene on chromosome 10, the Rad21 gene on chromosome 8 and the HDAC8 gene on the X chromosome. Most affected individuals have an abnormal gene as a result of a new gene mutation and do not have an affected parent. Other genes may be found to be associated with CdLS in the future.
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