Cornelia de Lange syndrome: milder presentations, diagnosis and support

Cornelia de Lange syndrome is a genetic condition that is usually present from birth. Contact describes children with the syndrome as being small at birth, having similar facial features and usually showing specific medical problems and intellectual disability. It is often shortened to CdLS.

The sources used for this guide describe CdLS as a spectrum. Contact notes that limb differences run from small hands and particularly short thumbs in mild cases to almost complete absence of the forearms in severe cases, and that children with the syndrome usually have slow development and significant learning disability. The sources do not give figures for how many people have milder features or at what age they are usually diagnosed, so this page does not either.

According to Contact, almost all children have similar facial features, including 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. Affected children often have an unusual marbled appearance to the skin on their arms and legs, particularly when they are cold.

Development is usually slow or very slow, and many have psychological and behavioural problems, including autistic spectrum conditions, poor sleep, social anxiety, compulsive behaviour and self-injurious behaviour. Contact notes that gastro-oesophageal reflux is very common and may be the cause of self-injurious behaviour, which is why it is important to recognise and treat it.

• Slow development and learning disability.

• Small stature and characteristic facial features.

• Limb differences of varying severity.

• Feeding difficulties and reflux.

• Heart defects, hearing problems and seizures.

Mutations in five genes, NIPBL, SMC1A, SMC3, RAD21 and HDAC8, have been identified as causing CdLS and CdLS-like conditions. Contact explains that NIPBL gene mutations are found in most people with typical CdLS, with the other genes much less common, and that the proteins these genes produce play important roles in directing development before birth.

Almost all cases arise as a result of a sporadic mutation, which means a new change not inherited from a parent. Very rarely CdLS can be inherited in an autosomal dominant pattern (NIPBL, SMC3 or RAD21) or an X-linked pattern (SMC1A or HDAC8). Genetic counselling should be sought by affected families, and prenatal testing in later pregnancies is possible through chorionic villus sampling or amniocentesis, while detailed ultrasound scanning may detect limb defects.

The diagnosis is based on a child showing the typical characteristics of the condition. Contact explains that molecular DNA analysis of the NIPBL gene from a blood sample allows confirmation in about 50 per cent of cases, and that DNA from skin can make a diagnosis in almost all typical cases. A negative blood test therefore does not by itself exclude CdLS.

Other investigations that are useful in a suspected case are hearing tests and an echocardiogram, which is a picture of the heart, to check for common defects.

There is no cure for CdLS and treatment is designed to relieve the symptoms experienced. Contact describes educational support and speech and language therapy to assist learning and speech, with some children unable to speak who may learn to communicate through sign language, and hearing aids helping some. Psychological and behavioural support can help with behavioural problems, and heart defects may be corrected by surgery. Occupational therapy and physiotherapy may assist with adapting to limb differences.

Epilepsy is described as a common and treatable complication, and reflux as very common and important to treat. The CdLS Foundation UK and Ireland website lists treatment guidelines and medical question-and-answer pages, and mentions a CdLS-specific wellbeing checklist to help parents, carers and professionals reduce challenging behaviour and improve wellbeing.

The CdLS Foundation UK and Ireland is a UK charity providing information and support to people affected by the syndrome and their families, and Contact describes it as holding mini conferences twice a year where families can meet.

A local paediatric or genetics service can advise on what is available in your area, and keeping a record of assessments such as hearing tests and heart scans makes it easier to share information between professionals as a child grows.

In the UK, diagnosis and genetic testing usually go through NHS paediatric and clinical genetics services, which can also provide counselling for other family members. Private genetic testing exists, but results are best interpreted by a genetics team that can also advise on the implications for relatives and for future pregnancies. Whichever route you use, ask for a written report of any gene variant found.