Genetic counseling for the 22q11.2 deletion

Abstract

Because of advances in palliative medical care, children with the 22q11.2 deletion syndrome are surviving into adulthood. An increase in reproductive fitness will likely follow necessitating enhanced access to genetic counseling for these patients and their families. Primary care physicians/obstetric practitioners are in a unique position to identify previously undiagnosed patients as they reach reproductive age and to refer them for genetic counseling. To date, most deletions are de novo, secondary to homologous recombination between low-copy repeat sequences located within 22q11.2. Nonetheless, both somatic and germ line mosaicism has been observed giving unaffected parents a small risk of recurrence. Once present though there is a 50% chance for a person with this contiguous deletion to have an affected child. With this in mind, a variety of prenatal monitoring techniques, as well as, preimplantation genetic diagnosis are available depending on the specific level of risk.

Sex differences in reproductive fitness contribute to preferential maternal transmission of 22q11.2 deletions

“…Future improvements in treatment could ameliorate the neuropsychiatric components of the phenotype that significantly affect fitness. Also, to our knowledge, and consistent with low rates reported elsewhere for comparably aged cohorts,41 42 there were no selective terminations on the basis of known or suspected 22q11.2 deletions in this sample. Expanded prenatal screening could dramatically affect both the overall incidence of 22q11.2 deletions and the observed fitness in carriers.…”

“…For example, adoption of genome-wide microarray technologies as a standard practice in prenatal screening could have a major impact on the rate of selective termination in pregnancies carrying 22q11.2 deletions, the majority of which would be spontaneous mutations. Currently, the possibility of selective termination mainly exists for the majority with major anomalies detectable on fetal ultrasound and those at 50% risk of transmission 41 42. For the latter, this would require that the parent already be diagnosed with 22q11.2DS, have received adequate genetic counselling, and that the salient information be recalled and acted upon.…”

Congenital Heart Disease in the Older Adult

“…256 Typical phenotypic features may be equally subtle in milder forms of 22q11.2 microdeletion syndrome, 255 with some patients identified only after the diagnosis of an affected child. 257 In suspected or confirmed genetic syndromes, a targeted search for other system involvement should be considered because of the important medical and prognostic implications of identifying a genetic syndrome in a patient with CHD. Patients with 22q11dele-tion syndrome can have other abnormalities that require management, including hypocalcemia, immunodeficiency, renal anomalies, and behavioral and neuropsychiatric disorders that are often late in onset.…”

Genetic Counseling in the Adult with Congenital Heart Disease: What is the Role?

“…Approximately half of all Turner syndrome women are diagnosed after their 15th year [36]. Typical phenotypic features may be equally subtle in milder forms of the 22q11.2 microdeletion syndrome [34], with some patients identified only after the diagnosis of an affected child [37]. A checklist for identifying ACHD patients who might benefit from genetic testing and counseling is of great clinical utility ( Table 2).…”