22q11.2 deletion syndrome: Multisystem disorder

The 22q11.2 deletion syndrome is a multisystem disorder caused by a small part of chromosome 22 that is missing. This deletion results in poor development of various body systems such as the brain, immune system, heart, parathyroid gland, skeleton, and palate, among others. The clinical presentation and severity of symptoms are highly variable, but symptoms are usually fully apparent in an older child. Patients with the disease receive treatment by multiple specialists who provide supportive treatment for all symptoms. The disease cannot be cured as of April 2018. Finally, the prospects are variable.

  • Synonyms of 22q11.2 deletion syndrome
  • Epidemiology of multisystemic disease
  • Causes: Due to random deletion of part of chromosome
  • Symptoms
  • Diagnosis and examinations
  • Therapy
  • Limited thymus gland function
  • Cleft palate
  • Heart defects
  • Hypoparathyroidism
  • Mental disorders and mental health care
  • Prognosis of 22q11.2 deletion syndrome
  • Complications

 

Synonyms of 22q11.2 deletion syndrome

The 22q11.2 deletion syndrome is sometimes also referred to as:

  • 22q11.2DS
  • autosomal dominant Opitz G/BBB syndrome
  • CATCH22
  • conotruncal anomaly facial syndrome (CTAF)
  • the Cayler cardiofacial syndrome
  • the conotruncal syndrome
  • the deletion 22q11.2 syndrome
  • the DiGeorge syndrome
  • the Sedlackova syndrome
  • Shprintzen syndrome
  • the velo-cardio-facial syndrome
  • the velocardiofacial syndrome (VCFS)

 

Epidemiology of multisystemic disease

Approximately 1 in 4,000 patients suffer from the 22q11.2 deletion syndrome. However, it is possible that more patients are suffering from the disease. Some patients have mild symptoms of the disease and do not seek medical attention, or else they have been misdiagnosed.

Causes: Due to random deletion of part of chromosome

The 22q11.2 deletion syndrome is a chromosomal disorder in which the 22q11.2 segment in one of the two copies of chromosome 22 is deleted. As a result, thirty to forty genes have disappeared. This often happens randomly during fertilization on the mother’s side or the father’s side during the development of the fetus. As a result, various body systems are poorly developed, which is reflected in a very variable clinical picture. Rarely is the condition hereditary because most patients have no family history of the disease. However, in approximately ten percent of patients with the 22q11.2 deletion syndrome, the disease can be passed on from parent to child via an autosomal dominant inheritance pattern.Eye problems sometimes occur / Source: Nufkin, Flickr (CC BY-2.0)

Symptoms

The symptoms of 22q11.2 deletion syndrome depend on the organ affected. The highly variable symptoms are mild to severe and are evident from birth or in childhood. The characteristic features of this syndrome are often very subtle in childhood and only become fully apparent when the child is older. In fact, the distinctive facial features associated with the condition are absent or more subtle in people of African American or other non-white descent.The following symptoms are possible:

  • abnormal facial features, such as a long face, an underdeveloped chin (micrognathia), small teeth, a downturned mouth, low-set and misshapen ears, and widely spaced eyes (ocular hypertelorism)
  • breathing problems
  • autoimmune diseases such as idiopathic thrombocytopenia purpura, autoimmune hemolytic anemia (premature destruction of red blood cells), autoimmune arthritis, and autoimmune thyroid disease
  • parathyroid abnormalities such as seizures, hypoparathyroidism (too little active parathyroid gland) and abnormal calcium and phosphorus metabolism
  • a blue skin color (cyanosis) secondary to poor circulation caused by heart defects such as a ventricular septal defect (hole between the lower chambers of the heart), truncus arteriosus (missing heart of the blood vessel) and tetralogy of Fallot (combination of four abnormal heart structures).
  • a cleft palate (cleft) or other palate disorders causing feeding problems
  • poor muscle tone
  • altered kidney function
  • slowed growth
  • delayed development such as delayed speech and other developmental disorders
  • frequent infections
  • behavioral problems such as ADHD (difficulty with attention and energy control) and autism spectrum disorder (autism: problems with social interaction, communication and behavior)
  • hearing loss
  • hypocalcemia (decreased calcium levels in the blood)
  • cramps in the mouth (mouth cramps), arm (arm cramps), throat (throat cramps) or hand (hand cramps)
  • lung diseases
  • eye problems such as coloboma (missing part of the eye), cataract (clouding of the eye lens), strabismus, drooping eyelid (ptosis), amblyopia (lazy eye), sclerocornea (hardening of the cornea), …
  • problems with the development of the larynx, trachea and esophagus (laryngotracheoesophageal anomalies)
  • psychological disorders such as schizophrenia (condition including delusions and hallucinations), depression, anxiety and bipolar disorder (mood disorder)
  • skeletal abnormalities such as extra fingers, toes or ribs, wedge-shaped spinal bones, craniosynostosis (premature fusion of the cranial sutures), scoliosis (sideways curvature of the spine)…
  • thymus gland abnormalities such as a T-lymphocyte deficiency
  • seizures
  • thrombocytopenia (decrease in platelets)
  • forms of cancer such as hepatoblastoma, renal cell carcinoma and Wilms tumor (form of kidney cancer in children with abdominal pain)

 

Diagnosis and examinations

Doctors diagnose 22q11.2 deletion syndrome with a specific blood test: a FISH analysis. This abbreviation stands for Fluorescent In Situ Hybridization. A doctor usually decides to have this blood test performed when a baby or child has a heart defect. Various heart defects are strongly associated with the condition.

Therapy

The treatment of the 22q11.2 deletion syndrome usually requires a number of specialists from different medical disciplines, such as a cardiologist, a surgeon, an endocrinologist, an occupational therapist, a physiotherapist, a geneticist, an immunologist, a pediatrician, a speech therapist and/or a specialist in infectious diseases. These treat all symptoms supportively as the multisystemic disease cannot be cured.

Limited thymus gland function

Patients who suffer from a poorly functioning thymus are not able to fight infections well. This causes various mild to moderate infections. The patient must be vaccinated, just like peers who are not affected. Normally, immune function improves as a patient ages. When the thymus is very seriously affected, the patient is at risk for serious infections. Therefore, the patient may need a thymus tissue transplant, a bone marrow transplant, a stem cell transplant, or a transplant of disease-fighting blood cells.

Cleft palate

Patients with palate damage benefit from surgical correction.

Heart defects

The doctor corrects most heart defects through surgery.

Hypoparathyroidism

Patients with an insufficiently functioning parathyroid gland receive vitamin D supplements or calcium supplements. In addition, they must take parathyroid hormone.

Mental disorders and mental health care

Patients with mental problems and psychological disorders benefit from therapists who work in mental health care, such as a psychologist or a psychiatrist. Sometimes medication is required to control or improve symptoms.

Prognosis of 22q11.2 deletion syndrome

It is impossible to provide an outlook for patients with 22q11.2 deletion syndrome because this requires consideration of the organ system affected and the severity of the symptoms present. Early diagnosis and treatment are important to prevent complications as much as possible.

Complications

A shortened lifespan occurs more quickly in patients with a congenital heart defect or a problem with the immune system. If the thymus is absent and the T cells are missing, premature death is possible.

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