Cornelia de Lange syndrome (CdLS) is a rare genetic condition that can affect multiple organs. CdLS may cause a range of symptoms, including intellectual disability and characteristic head and facial features.

CdLS is generally a congenital condition, which means the symptoms are apparent at birth. Most infants with CdLS will have low birth weight and then may experience failure to thrive. This can mean that they do not gain weight or grow at the expected rate. Evidence suggests that CdLS affects males and females in equal numbers.

In this article, we will discuss CdLS and outline its causes, risk factors, symptoms, diagnosis, and treatment.

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CdLS is a rare congenital condition that Dutch pediatrician Cornelia Catharina de Lange first described in 1933. The symptoms and their severity can vary from person to person. CdLS commonly causes intellectual disability. The condition also has several possible physical symptoms, including:

  • distinct head and facial features
  • restricted growth
  • hirsutism, which is the presence of excess body hair

People often do not report mild cases of CdLS, which means that people may underestimate its prevalence. However, evidence estimates that CdLS affects approximately 1 in 10,000–30,000 newborns.

CdLS is a genetic condition. It occurs as a result of changes in DNA sequences, which affect the production of certain proteins. These changes affect the proteins’ ability to perform their functions, leading to the symptoms of the condition. Scientists associate several different genes with CdLS.

Autosomal dominant CdLS

A person has two different versions, or alleles, of each gene. Every person inherits one allele from their biological father and one from their biological mother.

A person can inherit genetic conditions in many different ways. If a person must receive only one altered gene from a parent for a condition to occur, a medical professional will describe the condition as autosomal dominant. In some people, CdLS is autosomal dominant. Medical professionals associate the following autosomal genes with CdLS:

X-linked CdLS

X-linked genetic conditions are those that result from a gene variation on the X chromosome. Females typically have two X chromosomes, and males usually have only one. One female X chromosome is typically inactive, which means the genes on that chromosome do not function.

Therefore, X-linked conditions occur mostly in males, who typically have only one X chromosome. Carrier females usually do not present symptoms, as the inactive X chromosome is the one with the genetic variation.

However, because CdLS may follow a mostly X-linked dominant inheritance pattern, females often show similar findings to males. Medical professionals associate X-linked CdLS with the genes SMC1A and HDAC8.

Below are some of the symptoms of CdLS.

Intellectual disability and other developmental symptoms

Infants with CdLS often experience global developmental delay (GDD). An infant has GDD if they do not reach developmental milestones within the expected age range. GDD often involves a significant delay in two or more developmental areas in children aged 5 years or younger. Children with CdLS also commonly experience intellectual disability.

Additionally, people with CdLS may experience a range of behavioral difficulties, which may include:

  • aggression
  • self-injury
  • self-stimulatory behavior, such as repetitive or unusual body movements or noises

CdLS often presents alongside other mental health conditions, such as:

Face and head features

Infants with CdLS often display several common face and head features, including:

  • thick, arched eyebrows that meet in the middle
  • a short, upturned nose
  • a thin vermillion border of the lips
  • a cleft palate
  • delayed eruption of teeth
  • widely spaced teeth
  • long eyelashes that may be curly
  • a long philtrum — the groove between the nose and upper lip
  • a small skull
  • low set ears

Other physical symptoms

Many other possible physical symptoms may affect infants with CdLS, including:

  • Hirsutism: The presence of excess body hair is a common symptom of CdLS.
  • Gastroesophageal reflux disease (GERD): GERD occurs when stomach acid repeatedly flows back into a person’s esophagus. GERD is a common complication of CdLS.
  • Other gastrointestinal (GI) issues: People with CdLS may experience GI issues such as:
    • general complaints of nausea
    • vomiting
    • diarrhea
    • constipation
    • feeding difficulty
    • poor appetite
    • pyloric stenosis
    • gastrointestinal rotation
    • diaphragmatic hernias
  • Cardiac symptoms: People with CdLS may experience a range of cardiac issues, including:
    • heart murmurs
    • coarctation of the aorta
    • pulmonary stenosis
    • atrial or ventricular septal defects
  • Scoliosis: This is a sideways curve of the spine. Scoliosis affects approximately 39% of people with CdLS.
  • Other skeletal problems: Other possible skeletal problems in people with CdLS include:
    • partial toe fusion
    • a curved fifth digit
    • radial hypoplasia
    • a shortened sternum
    • a sunken sternum

Doctors will often make an initial diagnosis of CdLS based on clinical symptoms.

Medical professionals may observe a growth restriction in a fetus during an ultrasound scan. After birth, the newborn may present with failure to thrive and low birth weight. Newborns with CdLS often have a birth weight of less than 2.2 kilograms (4.8 pounds). As infants with the condition grow older, they are likely to have delayed growth and to be below the fifth percentile for weight.

Individuals with CdLS may experience a variety of symptoms that can vary in severity. These effects can cause the condition to closely resemble a few other genetic conditions, such as:

Therefore, medical professionals will often carry out genetic testing to confirm their CdLS diagnosis. A medical professional will take a blood or spit sample and then look for specific changes in the person’s DNA to confirm the CdLS diagnosis.

Treatment for CdLS often helps manage symptoms and support the person.

In some cases, a child may undergo surgery to address the following physical symptoms of CdLS:

  • cleft palate
  • cardiac anomalies
  • diaphragmatic hernias
  • GERD

A person may also undergo plastic surgery to help reduce excessive hair. A few orthopedic techniques may be effective for helping with limb problems. Other services that may be beneficial for infants with CdLS include:

A parent or caregiver for an infant with CdLS may wish to consult a dietitian to address certain feeding difficulties. Medical professionals may also recommend regular hearing and vision screenings for all infants with neurodevelopmental conditions.

CdLS often does not affect a person’s life expectancy. If a person develops any complications relating to the condition, their prognosis will depend on the severity and management of those complications.

CdLS is a rare genetic condition that may cause a range of symptoms, including intellectual disability and characteristic head and facial features. Other possible physical symptoms of the condition include hirsutism, skeletal problems, GI issues, and cardiac anomalies.

A medical professional will often make a diagnosis based on clinical symptoms. They can then use genetic testing to confirm their diagnosis. Treatment for CdLS often aims to manage the symptoms. An infant may undergo surgery to address certain physical symptoms. They may also benefit from physical therapy, occupational therapy, and speech therapy.