Genetic mutations are responsible for generating an immense amount of change or variation among people. However, when these alterations occur in a number of specific genes, they can lead to the appearance of congenital diseases or syndromes.

One of these conditions is Cornelia de Lange syndrome , which is expressed through a series of physical and mental characteristics. This article will describe its manifestations, causes and diagnosis.

What is Cornelia de Lange syndrome?

Cornelia de Lange syndrome (SCdL) is a congenital multiple malformative disease that is characterized by being inherited in a dominant way and by causing an alteration in the child’s development.

This syndrome manifests itself through a very characteristic facial phenotype , a delay in growth both prenatally and postnatally and by a disorder of intellectual development or cognitive deficits that may occur to a variable degree.

In addition, many times people suffering from Cornelia de Lange Syndrome also suffer from some kind of abnormality or malformation in their upper extremities.

Three types of phenotypes can be distinguished according to the intensity of the symptoms: the severe, moderate and mild phenotype.

According to the different investigations, the prevalence of this syndrome is one affected person out of every 45,000 to 62,000 births . However, most cases of Cornelia de Lange occur in families with dominant inheritance patterns.

Finally, estimating life expectancy is a very complicated task since it can vary from one person to another depending on the severity of the syndrome and associated pathologies.

Traditionally, the main cause of death was related to a misdiagnosis of the disease and associated pathologies. However, thanks to medical advances, both in diagnosis and treatment, this has been changed.

Clinical characteristics

Among the distinctive physical features of this disease we find a weight below the usual weight at birth, being below 2.2 kg . approximately. As well as a slow growth development, a low height and presence of microcephaly.

With regard to the facial phenotype, this usually presents united eyebrows and with pronounced angles, small nose, large eyelashes and thin inverted “V” shaped lips.

Other common signs of Cornelia de Lange syndrome are

  • Hirsutism .
  • Small hands and feet.
  • Partial fusion of the second and third toes
  • Curved pinkies.
  • Esophageal reflux .
  • Seizures.
  • Heart abnormalities.
  • Cleft palate .
  • Intestinal abnormalities.
  • Hearing and vision loss.

In terms of behavioral symptoms, children with Cornelia de Lange often exhibit self-injurious behaviors such as biting their fingers, lips, and upper extremities.


The causes of Cornelia de Lange syndrome are purely genetic. Within these genetic causes, there are two types of mutations that can cause this condition.

The main genetic alteration that results in Cornelia de Lange is a mutation in the NIPBL gene . However, there are other cases of this syndrome caused by mutations in the genes SMC1A and SMC3 and in a smaller proportion the mutations are found in the genes HDAC8 and RAD21.

The NIPBL gene has a major role in human development and is already responsible for encoding the protein delangin. This protein is one of the proteins responsible for controlling the activity of chromosomes during cell division.

Also, the protein delangina media in the tasks of other genes responsible for the normal development of the fetus, specifically those genes responsible for the development of the tissues that will later form the limbs and face.


There is still no established protocol for the diagnosis of Cornelia de Lange syndrome, and clinical data must be used. However, the clarity and visibility of the symptoms make its diagnosis relatively easy .

Through the study of characteristic facial features, the assessment of intellectual performance and the measurement of pondo-state growth, an effective diagnosis of this syndrome can be made.

While this diagnosis is relatively simple, there are a number of difficulties when dealing with conditions with a mild phenotype. The phenotypes that imply difficulties at the time of diagnosis are

Mild phenotype

They are not usually diagnosed until after the neonatal period. In these cases no anomalies are shown in the extremities and both the general phenotype and intelligence are not very altered.

Moderate or variable phenotype

In these cases the great variability in both features and expressions makes it difficult to diagnose.

Through the study of characteristic facial features, the assessment of intellectual performance and the measurement of pondo-state growth, an effective diagnosis of this syndrome can be made.

Due to these difficulties, diagnosis during the prenatal period is only plausible in siblings of people affected by the disease, when there is some kind of abnormality in family members, in cases of hydrocephalus or in intrauterine developmental delays evident on ultrasound scans.

What options or needs do people with SDdL have?

As mentioned above, the degree of intellectual development of the people with Cornelia de Lange may vary from one to another, each of them will have the capacity to prosper according to their personal possibilities and the aids and supports provided by their family and social environment .

Unfortunately, both language and communication in general tend to be severely affected. Even in the slightest cases the evolution of these aspects can be seriously compromised.

Due to the needs of children with Cornelia de Lange it is advisable to provide them with a calm and relaxed environment, eliminating any element that may be disturbing, distressing or threatening to the child. In this way you will avoid reinforcing tendencies towards hyperactivity, irritability and self-aggressive behaviour .

The main objective when interacting or living with children with Cornelia de Lange syndrome is to perceive and feel through the child’s conditions, without forcing them to perceive things as we do.