Cornelia de Lange syndrome
Also known as: Amsterdam Dwarf syndrome; Amsterdam Dwarfism; Brachman de Lange; Brachmann syndrome; De Lange I syndrome
Cornelia de Lange syndrome (CdLS) affects 1 in 10,000 to 30,000 babies born. Children with the syndrome are small at birth, have similar facial features and usually exhibit specific medical problems and intellectual disability.
Last updated August 2016 by David FitzPatrick MD, Professor and Consultant Geneticist, MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.
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Children with CdLS usually have slow or very slow development and significant learning disability. Many have psychological and behavioural problems, including autistic spectrum conditions (see entry Autism Spectrum conditions), poor sleep, social anxiety, compulsive behaviour and self-injurious behaviour.
Many children have limb abnormalities, ranging from having small hands and particularly short thumbs in mild cases, to almost complete absence of the forearms in severe cases. Affected children will often have an unusual marbled appearance to the skin on their arms and legs, particularly when they are cold.
Almost all the children have similar facial features, including hirsutism (excessive hair), thin and arched eyebrows that often meet in the middle, long eyelashes, low-set ears, widely spaced teeth, a short upturned nose and down-turned lips.
Medical complications are very common in CdLS, including feeding and bowel problems, particularly gastro-oesophageal reflux (GERD). Heart defects are also common, affecting at least ten per cent of those with CdLS. Most children have hearing problems and seizures (see entry Epilepsy) are another common feature.
Mutations in five genes,NIPBL, SMC1A, SMC3, RAD21 and HDAC8 have been identified as causing CdLS and CdLS-like conditions. NIPBL gene mutations have been identified in most people with typical CdLS, with mutations in the other genes being much less common. The proteins produced from all these genes play important roles in directing development before birth.
The diagnosis is based on a child demonstrating typical characteristics of the condition. Molecular (DNA) analysis of the NIPBL gene from a blood sample allows confirmation in about 50 per cent of cases. Skin DNA can make a diagnosis in almost all typical cases. Other useful investigations in a suspected case of CdLS are hearing tests and echocardiogram (pictures) of the heart to check for common defects.
There is no cure for CdLS. Treatment is designed to alleviate the symptoms experienced. Educational support and speech and language therapy will assist learning and speech development. Some children will be incapable of speech and may learn to communicate via sign language – hearing aids may help a proportion of children. Psychological and behavioural support can assist with behavioural problems. Heart defects may be corrected by surgery. Occupational therapy and physiotherapy may assist with adapting to limb deformity. It is important to recognise and treat GERD, which is very common and may be the cause of self-injurious behaviour. Epilepsy is also a common and treatable complication.
Almost all cases arise as a result of sporadic mutation. Very rarely CdLS can be inherited as an autosomal dominant (NIPBL, SMC3 or RAD21) or X-linked (SMC1A or HDAC8) pattern of inheritance. Genetic counselling should be sought by affected families.
Prenatal testing of subsequent pregnancies in an affected family is possible by molecular (DNA) testing of samples collected by chorionic villus sampling or amniocentesis. Detailed ultrasound scanning may detect limb defects.
CdLS Foundation UK & Ireland
The Foundation is a Registered Charity in England and Wales No. 1054033. It provides information and support to people affected by Cornelia de Lange Syndrome. The Foundation holds mini conferences twice a year where families can meet each other and get the chance to talk informally about the condition and learn from the experiences of others.
Group details last updated August 2016.