Cornelia de Lange Syndrome


What is Cornelia de Lange Syndrome?

Cornelia de Lange Syndrome (CdLS) is a genetic disorder which affects the developmental process. It can cause physical, intellectual, and medical problems of a child. It is a congenital condition, but is not always diagnosed promptly at birth [1].

The disorder was named after Cornelia Catharina de Lange, a Dutch physician who described the condition in 1933. It is also known as Brachmann syndrome, Brachmann-de Lange syndrome, and Amsterdam dwarf syndrome [2].


Cornelia de Lange Causes

In most cases of Cornelia de Lange syndrome, it has been found that it occurs sporadically [3]. Also, generally, there is no traced family condition of the disorder. Though it can be said that the cases are sporadic genetic mutations, there are three genes which are associated with its occurrence [4]. These are:

  • SMC1A
  • SMC3

These three genes play vital roles in the production of proteins that are essential in the development, after birth. These proteins produced by NIPBL, SMC3, and SMC1A, are important in the structure regulation and chromosomes organization. They are also responsible for the repair of the damaged DNA, and the activity regulation of genes for development of face, limbs, and other body parts.

When these genes become mutated, Cornelia de Lange syndrome can result, due to the disruption in the regulation of genes occurring at the early stages of development. According to studies, when mutations in SMC3 and SMC1A take place, the signs and symptoms are milder, than those who have NIPBL gene mutations. [5]


Cornelia de Lange Syndrome Symptoms

Major Characteristics

Patients who are diagnosed with Cornelia de Lange syndrome may exhibit all or just a few of the following traits:

1. Birth weight, head size, and growth

  • Birth weight: In most children with the CdLS, the birth weight ranges from 1-10 lbs. The average birth weight is 5 lbs.
  • Birth length: The children with CdLS are usually short in stature; most of them have the birth length of 18 inches.
  • Head size: Microcephaly (small head size) is a common finding related with the condition.

2. Developmental problems

  • Intellectual delays which range from mild to severe.
  • Learning challenges
  • Severe language delays

3. Behavioral problems

  • Self-injury: This is a usual occurrence happening to children with CdLS at the age of 12 and above. This is associated with delayed response to the pain which may be attributed to the mental retardation and autism. Includes hand-biting, and head-banging.
  • Sleep disturbances
  • Hyperactivity, compulsive behaviours
  • Social anxiety

4. Gastrointestinal problems

  • Gastroesophageal Reflux Disease (GERD): Present in approximately 85% of people with CdLS. This contributes to the pain felt with eating and hyper activity.
  • Pyloric Stenosis: Most common cause of persistent vomiting in newborns with CdLS.
  • Diaphragmatic hernia
  • Feeding problems, poor appetite, diarrhea, constipation

Secondary Characteristics

1. Facial features

Prominence in the facial features are noticed in most children with CdLS. These include:

  • Synophrys: A condition in which the eyebrows which are thin, meet at the midline
  • Thin downturned lips
  • Low-set ears
  • Cleft palate or high-arched palate, wide teeth spacing
  • Long eyelashes
  • Nose with short and upturned appearance

2. Limb abnormalities

The usual features found in individuals with CdLS include:

  • Hands and feet are small
  • Clinodactyl: Incurved fifth fingers
  • Thumbs are placed proximally to other fingers.
  • Missing fingers, hands, or forearms
  • Abnormalities on the upper limbs
  • Second and third toes are partially joined

Problems in other systems

1. Cardiovascular disorders

In 46 % of individuals with CdLS, congenital malformations of the heart take place. These are:

  • Tetralogy of Fallot
  • Atrial or ventricular septal defect
  • Pulmonary stenosis

2. Respiratory diseases

  • Pneumonia
  • Upper Respiratory Tract Infections

3. Hearing problems

  • This is due to the narrowing found at the external auditory canals.
  • Hearing loss may be mild to severe.

4. Ophthalmic abnormalities

  • Myopia: Nearsightedness
  • Ptosis: Drooping eyelids
  • Nystagmus: Uncontrollable movements of the eyes

5. Genitourinary problems

  • Impaired kidney functions
  • Problems like: Urethral reflux, kidney cysts

6. Other noted problems in CdLS

  • Seizures
  • Heat intolerance
  • Decreased or absent pain sensation [1, 4, 6]


Cornelia de Lange Syndrome Photos

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Picture 1: Cornelia de Lange Syndrome photo

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Picture 2: Cornelia de Lange Syndrome photo

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cornelia de lange syndrome pic3

Picture 3: Cornelia de Lange Syndrome photo

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Cornelia de Lange Syndrome Diagnosis

The diagnosis of Cornelia de Lange Syndrome is evaluated based on the observed signs and symptoms manifested by the child. It includes medical history, physical assessment of symptoms, and laboratory workups.

Laboratory Workups

1. Genetic diagnosis

  • This is a test for screening the genes for presence of mutations in NIPBL and SMC1A genes.
  • Confirmatory diagnostic test
  • The results involves prenatal testing for future pregnancies and family-specific mutation

2. CBC count

  • A common finding among CdLS individuals is thrombocytopenia.

Imaging studies

1. Radiography

This may show the following findings

  • Long-bone and finger abnormalities
  • Thirteen ribs
  • Aspiration pneumonia
  • GERD, intestinal obstructions
  • Abnormalities in the pelvis

2. Ultrasound

This is used for assessment of the kidney and urinary tract. Findings may reveal:

  • Kidney abnormalities
  • Renal cysts and ectopia
  • Pelvic dilatation
  • Voiding cystourethrography: This is recommended for the assessment of reoccurrence of urinary tract infections.

3. Echocardiography

  • Ordered by the physician for congenital heart disease.

4. MRI or CT scan

  • Enlarged ventricles, basal cisterns
  • Thinning of white matter
  • Hypoplasia of the brainstem and cerebrum

Other tests

1. Chromosomal studies

  • Indicated for ruling out of uncertain diagnosis

2. Hearing evaluation

  • Most people with CdLS have sensorineural hearing loss that needs to be evaluated properly.

3. Endocrinopathies

  • This is for the observation of the levels of thyroid hormones, such as the growth hormones. [3]


Cornelia de Lange Syndrome Treatment

Medical Intervention

Prompt treatment for CdLS patients is essential to address problems such as hearing and visual impairments, feeding problems, system disorders, and others.

1. Intervention for psychomotor delay

  • Computer programs: This is advised to enhance visual memory.
  • Tactile stimulation
  • Perceptual organizational tasks
  • Education to help the individual perform activities of daily activities

Surgical Interventions

Conditions which may require surgery involve:

1. Digestive system disorders

  • GERD
  • Pyloric stenosis
  • Intestinal obstructions
  • Cleft palate

2. Genitourinary abnormality

  • Undescended testis

3. Other problems

  • Nasal polyps
  • Lacrimal duct stenosis
  • Hip dislocation


As of the moment, there is no established drug therapy indicated for Cornelia de Lange syndrome. However, medications may be used to treat symptoms, such as GERD, seizures, and behavioural symptoms. [3]


Cornelia de Lange Syndrome Prognosis

In most cases of CdLS, children were able to survive until adulthood. However, there are some cases in which children die earlier which may be caused by heart anomalies and gastrointestinal defects. Also, intellectual disability is a common problem. Most of them need supervision in their activities, especially, to the working situations in adults. [7]











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