What is Cornelia de Lange Syndrome?

The first case of Cornelia de Lang Syndrome was documented in 1916 by Wilfred Robert Brockmann. The second in 1933 by Dutch paediatrician Cornelia Catherina de Lange and it is after her that the disorder is named, although it was formerly called the Brockmann-de Lange Syndrome and is known colloquially as Amsterdam Dwarfism or Bushy Syndrome. Today, Cornelia de Lange Syndrome is referred to by the acronym CdLS.

A Genetic Mutation

Cornelia de Lange Syndrome is a genetic disorder present from birth, although not always diagnosed from birth. Whilst there is an hereditary aspect to Cornelia de Lange Syndrome and mutation in specific genes can point to patterns of inheritance, most cases result from a new genetic mutation in people with no family history of the condition, and in 30% of cases the specific cause is unknown. Cornelia de Lange Syndrome affects 1 in 10,000-30,000 live births, although experts suspect many mild cases remain undiagnosed.

The Genes that Mutate

Specifically, the genes that mutate are NIPBL, SMC1A, HDAC8, RAD21, SMC3. The mutation interferes with the Cohesion Complex, a group of proteins that play a crucial role in directing pre-natal development. Symptoms caused by SMC1A, RAD21 and SMC3 tend to be milder than those caused by NIPBL. HDAC8 mutations can be tied to specific abnormalities, such as, delayed closing of the anterior fontanelle, dental problems and widely spaced eyes and, as with NIPBL, individuals may have significant intellectual impairment.

General Symptoms of CdLS

A range of symptoms are caused by Cornelia de Lange Syndrome and these can vary from mild to sever and include, abnormalities in the bones of the arm, hands and fingers. Facial features can be distorted by arched eyebrows that often meet in the middle, abnormally long lashes, teeth spaced some distance apart and low-set ears. Other manifestations include excessive bodily hair, small heads, hearing and digestive problems, and a cleft palate. Behavioural problems are similar to those sometimes demonstrated in people on the autistic spectrum.

Cornelia de Lange Affects on Behaviour

Many people with Cornelia de Lange Syndrome show no sign of behavioural problems, in others they can be severe and include, self-injury, self-stimulation, a strong reaction to every day stimuli which continues after the stimulus has been withdrawn. There can be a lack of sensitivity to pain or a heightened sensitivity to it, both of which point to underlying neurological problems. Hyperactivity and a short attention span are often present and carers note dysrhythmic or irregular patterns in eating, sleeping and emotional response. Whilst many of these can be dealt with by a paediatrician experienced in behavioural problems, persistent issues need to be addressed by a behavioural psychologist or child psychiatrist and inevitably, severe and long-term behavioural problems require the long-term commitment of a specialist.


Small teeth and teeth crowded together can be consequent of small jaw development in people with CdLS. Dental hygiene can be problematic and exacerbated by gastroesophageal reflux where the presence of digestive acids in the mouth rot the teeth. Early dental revaluation and on going treatment and preventative strategies can help overcome most issues. Cleft palates are common in cases of CdLS and these can cause problems with the ear canal and recurrent ear infections. If cleft palates are repaired shortly after birth, problems with eating and speaking which might otherwise have manifested, can be prevented. Nevertheless, hearing loss can range from mild to profound and can change overtime. Narrow ear canals and difficulties in carrying out a thorough examination due to patient behaviour, present a challenge to any audiologist.


Strabismus, Nystagmus, severe myopia and Ptosis or eye drooping have all been observed in CdLS cases. Early assessment by an optometrist is the first step in implementing corrective action for whatever optical defect the patient has. It should also be noted that some children with CdLS do not display normal gaze behaviour.


Research shows that between 20%-30% of children with Cornelia de Lange Syndrome have some form of congenital heart defect. Sever conditions are easily diagnosed at birth; other less severe issues are more difficult to spot. Early referral of all CdLS babies to a paediatric cardiologist is strongly recommended. Congenital heart disease can be a factor in growth issues and lack of stature.

Speech and language

Only a small percentage of Cornelia de Lange patients show no difficulties with speech. Most have issues, such as, errors in articulation, use of sound substitutes or distorted consonants, there can also be speech apraxia. Early intervention and speech therapy can, in many cases, result in significant improvement.


The onset of puberty, physically, emotionally and behaviourally is in line with typical individuals, although mood swings and other behavioural problems can be more sever. Carers also often have to consider methods of preventing unwanted pregnancies.


Those with Cornelia de Lange Syndrome can be sensitive to temperature, taste, texture, the environment in which the food is taken and by those present, including feeders when that is necessary. Appetite can be affected by digestive complaints referred to earlier and other gastric problems including vomiting and gaseous distension.

Developments Skills

Early intervention and the application of appropriate stimuli can play a major role in the development of those with CdLS. An average IQ score of 53 for CdLS patients was derived from research done. 53 is in the range which points to moderate mental retardation. However, playing to areas of strength, such as, visual-spatial memory through the use of computers and tactile stimulation has proved an effective development strategy.


Education play a key role alongside medical related issues and is crucial in overcoming many problems. Educational plans, careful education placement where teaching can be unique to the individual, helping CdLS patients to minimise their physical limitations and issues and helping them to develop to their fullest potential requires an interdisciplinary approach from speech and occupational therapists, physical therapists, teachers physicians and of course parents and carers.

The Cornelia de Lange Foundation is based in Avon Connecticut it provides a free information package on request and works to support families, professional and others.