22q11.2 deletion syndrome

Disease Description (Causes and Symptoms)

• Definition: A chromosomal abnormality syndrome (18p monosomy) caused by deletion of the short arm (p, short arm) of chromosome 18. Although rare, it presents with characteristic facial and neurodevelopmental phenotypes.
• Cause/Pathophysiology: Most cases result from de novo deletions (approximately 85%), while some may originate from structural chromosomal abnormalities in a parent (such as a translocation), making parental chromosomal testing necessary. Clinical manifestations vary depending on the extent of the deletion (that is, how many genes are lost). Some cases are accompanied by central nervous system developmental abnormalities, such as holoprosencephaly.
• Main symptoms: Intellectual disability (mild to moderate; an IQ range of approximately 25–75 has been reported in some cases), ptosis, strabismus, hypertelorism (eyes appearing widely spaced), microcephaly, micrognathia (small lower jaw), large protruding ears, a large drooping mouth, growth delay, cardiac defects (congenital heart disease), immunoglobulin A (IgA) deficiency, dental caries, male-pattern baldness, and others. When holoprosencephaly is present, the neurological prognosis is poorer—many individuals without holoprosencephaly survive into adulthood.
• Diagnosis: Confirm the extent of the deletion with standard cytogenetic testing (peripheral blood chromosome testing, karyotyping), chromosomal microarray (CMA), or FISH. Depending on the clinical findings, brain MRI (to evaluate for holoprosencephaly when necessary), echocardiography (to evaluate cardiac defects), hearing and vision tests, and immune testing (especially IgA) are recommended.

Treatment

• General principles: Since there is no treatment that can restore the causative genes, multidisciplinary and conservative management tailored to the symptoms is the mainstay. Early intervention and ongoing rehabilitation are important for improving development and function.
• Development and rehabilitation: Intensive early developmental intervention (physical therapy, occupational therapy, and speech therapy), special education, and social support programs. Psychosocial interventions for behavioral and learning problems.
• Medical/surgical treatment:
  • Congenital heart defects: If a cardiac defect is present, medication or, when necessary, surgical correction is performed by a pediatric cardiology department.
  • Ophthalmologic problems: Strabismus and ptosis may require Botox, glasses, patch therapy, or surgical correction to prevent impaired visual development (amblyopia).
  • Hearing and dental care: Regular hearing tests, dental examinations, and prevention and treatment of dental caries.
  • Neurological symptoms: If seizures occur, medication such as anticonvulsants may be used.
  • Immunodeficiency (such as IgA deficiency): In cases of recurrent infections, immunological evaluation followed by recommended vaccinations (as directed by a physician) and infection management when necessary.
• Medications: Medications according to the symptoms (such as anticonvulsants and behavioral medications). There are no medications specifically targeted to this condition.
• Genetic counseling: Parental chromosomal testing and assessment of the risk in future pregnancies, as well as counseling regarding prenatal diagnosis (CVS/amniocentesis or noninvasive prenatal testing/microarray during pregnancy), are recommended.
• Lifestyle management and precautions: Regular monitoring of growth and development; scheduling cardiac, neurological, ophthalmologic, dental, and hearing examinations; infection prevention (vaccinations and hygiene); and management of nutrition and dental hygiene.

Checklist Before an Outpatient Visit (Including Example Questions)

• Items to prepare and points to confirm:
  • A list of currently used medications (including prescription drugs, nonprescription drugs, and supplements)
  • Copies or reports of previous test results (chromosome tests, echocardiography, MRI, blood tests, etc.)
  • Developmental history: Records of when the patient sat, crawled, walked, and spoke, along with recent changes
  • History of infections, hospitalizations, and surgeries, and vaccination records
  • Family history (congenital anomalies, intellectual disability, recurrent miscarriages, or chromosomal abnormalities in parents or siblings)
  • Recent records of growth (height and weight), and changes in sleep, eating, or behavior
• Common topics asked about at an outpatient visit (examples):
  • When the symptoms began and how they have progressed
  • Current daily life and school adjustment, and rehabilitation services currently being received
  • Whether seizures, difficulty breathing, feeding difficulties, or frequent infections are present

General Examples of Questions to Ask the Doctor

• "What is the cause of this chromosomal deletion, and what is the risk of recurrence for our family?"
• "What prognosis can be expected, and what tests and follow-up examinations are needed?"
• "What can we do to reduce the risk of major complications for our child (or the patient)?"
• "What rehabilitation and educational programs are recommended, and when should they begin?"
• "What are the expected benefits and side effects of the medication (or surgery)?"

Examples of Condition-Specific Questions

• "Could you tell us the size of our (or our child's) chromosomal deletion? How might specific genes included in the deletion affect the prognosis?"
• "Even if there are no signs of cardiac (or brain) abnormalities, what tests (for example, echocardiography, brain MRI, or immune testing) should be performed regularly, and how often?"