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Cornelia de Lange Syndrome.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
2005 Sep 16 [updated 2016 Jan 28].

Author information

1
Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
2
Genetic Counselor, Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania

Excerpt

CLINICAL CHARACTERISTICS:

Classic Cornelia de Lange syndrome (CdLS) is characterized by distinctive facial features, growth retardation (prenatal onset; <5th centile throughout life), hirsutism, and upper-limb reduction defects that range from subtle phalangeal abnormalities to oligodactyly (missing digits). Craniofacial features include synophrys, highly arched eyebrows, long eyelashes, short nose with anteverted nares, small widely spaced teeth, and microcephaly. IQ ranges from below 30 to 102 (mean: 53). Many individuals demonstrate autistic and self-destructive tendencies. Frequent findings include cardiac septal defects, gastrointestinal dysfunction, hearing loss, myopia, and cryptorchidism or hypoplastic genitalia. Individuals with a milder phenotype have less severe growth, cognitive, and limb involvement, but often have facial features consistent with CdLS.

DIAGNOSIS/TESTING:

Diagnosis is based on clinical findings and/or the identification of a heterozygous pathogenic variant in NIPBL, RAD21, or SMC3 or a hemizygous pathogenic variant in HDAC8 or SMC1A.

MANAGEMENT:

Treatment of manifestations: Aggressive management of gastroesophageal reflux with assessment of potential gastrointestinal malrotation in all affected individuals; consideration of fundoplication if reflux is severe. Supplementary formulas and/or gastrostomy tube placement to meet nutritional needs as necessary. Physical, occupational, and speech therapy to optimize psychomotor development and communication skills. Standard treatment for hearing loss, cardiac defects, seizures, vesicoureteral reflux, and cryptorchidism. Prevention of secondary complications: Preoperative evaluation for thrombocytopenia and cardiac disease with careful monitoring of the airway during anesthesia; malignant hyperthermia precautions. Surveillance: Annual GI evaluation, monitoring of growth and psychomotor development; routine eye and hearing evaluations, and monitoring of heart and kidney abnormalities.

GENETIC COUNSELING:

NIPBL-related CdLS, RAD21-related CdLS, and SMC3-related CdLS are inherited in an autosomal dominant manner; HDAC8-related CdLS and SMC1A-related CdLS are inherited in an X-linked manner. The majority of affected individuals have a de novo heterozygous pathogenic variant in NIPBL; fewer than 1% of individuals with NIPBL-related CdLS have an affected parent. When the parents are clinically unaffected, the risk to the sibs of a proband with NIPBL-related CdLS is estimated to be 1.5% because of the possibility of germline mosaicism. The risk to sibs of a proband with HDAC8-related CdLS or SMC1A-related CdLS depends on the status of the proband's mother. Prenatal testing for pregnancies at increased risk is possible for families in which the pathogenic variant has been identified.

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