An Introduction for Parents of Newly Diagnosed Children
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Summary +
Disease characteristics. Individuals with the 22q11.2 deletion syndrome (del 22q11.2) have a range of findings, including congenital heart disease (74% of individuals), particularly conotruncal malformations (tetralogy of Fallot, interrupted aortic arch, ventricular septal defect, and truncus arteriosus); palatal abnormalities (69%), particularly velopharyngeal incompetence (VPI), submucosal cleft palate, and cleft palate; characteristic facial features (present in the majority of Caucasian individuals); and learning difficulties (70-90%). Seventy-seven percent of individuals have an immune deficiency regardless of their clinical presentation. Additional findings include: hypocalcemia (50%), significant feeding problems (30%), renal anomalies (37%), hearing loss (both conductive and sensorineural), laryngotracheoesophageal anomalies, growth hormone deficiency,… Read More
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Diagnosis +
Clinical Diagnosis
The diagnosis of the 22q11.2 deletion syndrome is suspected in individuals with a range of findings that often includes some combination of the following:
Congenital heart disease (particularly conotruncal malformations)
Palatal abnormalities [especially velopharyngeal insufficiency (VPI)]
Hypocalcemia
Immune deficiency
Learning difficulties
Characteristic facial features
Less frequently seen functional differences:
Severe dysphagia
Growth hormone deficiency
Autoimmune disease (thrombocytopenia, juvenile rheumatoid arthritis, Grave's disease, vitiligo, neutropenia, hemolytic anemia)
Hearing loss (sensorineural and conductive)
Psychiatric illness
Other structural anomalies:
Skeletal findings: pre and postaxial polydactyly of the hands and postaxial polydactyly of the feet, supernumerary ribs, hemivertebrae, craniosynostosis
Genitourinary tract anomalies: renal agenesis, hydronephrosis, multicystic/dysplastic kidneys, duplicated kidney, horseshoe kidney, absent uterus, hypospadias, inguinal hernia, and cryptorchidism
Laryngotrachealesophageal… Read More
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Clinical Description +
Natural History
Findings in 250 individuals (48% male; 52% female) with 22q11.2 deletion syndrome are summarized below [McDonald-McGinn et al 1999b]. In unpublished data on 600 individuals, the percentages for the following findings remain the same [Author, unpublished data 2005].
Thirty-three percent of individuals were five years of age or younger. Marked inter- and intrafamilial variability is observed.
Heart. Congenital heart defects are present in 74% of affected individuals and are the major cause of mortality (>90% of all deaths) in this diagnosis [McDonald-McGinn et al 2001] (Table 2).
Table 2. Cardiac Findings in 222 Individuals with 22q11.2 Deletion Syndrome
Cardiac Finding% of Affected Individuals
Tetralogy… Read More
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Differential Diagnosis +
For current information on availability of genetic testing for disorders included in this section, see GeneTests Laboratory Directory. —ED.
Each of the anomalies seen in the 22q11.2 deletion syndrome can be found as an isolated anomaly in an otherwise normal individual.
Up to 8% of individuals with an isolated palatal cleft, including submucosal cleft, may have deletion 22q11.2, making this the most common genetic syndrome associated with palatal clefts. Conversely, the 22q11.2 deletion syndrome is the most common genetic basis of congenital velopharyngeal incompetence.
Disorders with overlapping features:
Smith-Lemli-Opitz syndrome (when polydactyly and cleft palate are present). Smith-Lemli-Opitz syndrome is associated with elevated serum concentration… Read More
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Management +
Evaluations Following Initial Diagnosis
To establish the extent of disease in an individual diagnosed with 22q11.2 deletion syndrome, the following evaluations are recommended:
Neonatal period
Measurement of serum ionized calcium concentration to assess for hypoparathyroidism, followed by a formal endocrinology evaluation if abnormal
Measurement of absolute lymphocyte count; a low absolute lymphocyte count necessitates evaluation of T- and B-cell subsets and referral to an immunologist.
Evalution of humoral immune response
Renal ultrasound examination to evaluate for structural renal defects
Chest x-ray to evaluate for thoracic vertebral anomalies
A baseline cardiac evaluation by a cardiologist that includes a chest x-ray, ECG and echocardiogram; if a vascular ring is suspected,… Read More
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Genetic Counseling +
Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. To find a genetics or prenatal diagnosis clinic, see the GeneTests Clinic Directory.
Mode of Inheritance
The 22q11.2 deletion syndrome is a… Read More
