Cornelia de Lange Syndrome

Cornelia de Lange Syndrome aka CdLS is a little known genetic disorder that can lead to severe developmental anomalies. It affects both the physical and intellectual development of a child. Exact incidence is unknown, but is estimated at 1 in 10,000 to 30,000.^[1]

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Causes

A gene responsible for CdLS—NIPBL on Chromosome 5—was discovered in 2004 by researchers at Children’s Hospital of Philadelphia.^[2] In 2006, a second gene—SMC1A on the X chromosome—was found by Italian scientists. A third gene discovery was announced in 2007. The gene SMC3 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.

The vast majority of cases are due to spontaneous mutations, although the defected gene can be inherited from either parent, making it autosomal dominant.

History

The first ever documented case was in 1916 by Dr. W. Brachmann^[3] followed up by Dr. Cornelia de Lange,^[4] a Dutch pediatrician, in 1933 after whom the disorder has been named.

Diagnosis

The diagnosis of CdLS is primarily a clinical one based on signs and symptoms (see below) observed through an evaluation by a physician, including a medical history, physical examination, and laboratory tests. Since 2006, testing for NIPBL and SMC1A has been available through the University of Chicago [1]. This is best accomplished through a referral to a genetics specialist or clinic.

CdLS is thought to be underdiagnosed and frequently misdiagnosed.^{[citation needed]}

Features and characteristics

Following are the features and characteristics which help in spotting this disorder:

• Low birth weight (usually under 5 pounds / 2.5 kilograms)
• Delayed growth and small stature
• Developmental delay
• Limb differences (missing limbs or portions of limbs)
• Small head size (microcephaly)
• Thick eyebrows, which typically meet at midline (synophrys)
• Long eyelashes
• Short upturned nose and thin downturned lips
• Long philtrum
• Excessive body hair
• Small hands and feet
• Small widely spaced teeth
• Low-set ears
• Hearing impairments
• Vision abnormalities (e.g., ptosis, nystagmus, high myopia, hypertropia)
• Partial joining of the second and third toes
• Incurved 5th fingers
• Gastroesophageal reflux
• Seizures
• Heart defects
• Cleft palate
• Feeding problems

Children with this syndrome are often found to have long eyelashes, bushy eyebrows and synophrys (joined eyebrows). Body hair can be excessive and affected individuals are often shorter than their immediate family members.

CdLS can give rise to its own array of complexities. Children with CdLS often suffer from gastrointestinal tract difficulties, particularly gastroesophageal reflux. Vomiting, intermittent poor appetite, constipation, diarrhea or gaseous distention are known to be a regularity in cases where the GE tract problems are acute. However, symptoms may range from mild to severe.

CdLS may also include a number of behavior problems, including self-stimulation, aggression, self-injury or strong preference to a structured routine. Many children with CdLS exhibit autistic-like behaviors and are on the autism spectrum.

Behavior problems in CdLS are not inevitable. Many behavior issues associated with CdLS are reactive (i.e., something happens within the person's body or environment to bring on the behavior), and cyclical (comes and goes). Often, an underlying medical issue causes a change in behavior. Once the medical issue is treated, the behavior diminishes.

Treatment

Often, an interdisciplinary approach to therapy and treatment of any medical issues that arise is recommended. A team for promotion of the child's well being often includes speech, occupational and physical therapists, teachers, physicians, and most importantly the parent(s). Treatment protocols can be viewed at http://www.cdlsusa.org/treatment_protocols.shtml.

Support

United States

The Cornelia de Lange Syndrome (CdLS) Foundation is a national, nonprofit, family support organization based in Connecticut. The Foundation provides a host of services that attract, educate, and unite families touched by CdLS.

Education & Information: A hallmark service of the CdLS Foundation has been to provide detailed materials for public education and information. Since the first publication of the bi-monthly newsletter, Reaching Out, in 1977, the Foundation has kept families and others informed on issues relevant to the syndrome. In addition to Reaching Out, the Foundation produces and distributes several other publications on the syndrome, as well as a free video [2].

Family Support: When someone is in need of assistance, the Foundation's family service coordinators are prepared to help. Calls placed to toll-free support lines are answered by caring professionals who are willing to listen. The Foundation web site www.cdlsusa.org also features an Ask the Doctor [3] forum.

Out in the community, volunteer regional coordinators assist the Foundation by reaching out to new families, uniting old ones, and providing peer-to-peer support. Bi-annual national conferences provide families with individual consultations, presentations from experts, and opportunities to meet with others in similar situations.

References