Clinical and molecular studies in full trisomy 22: Further delineation of the phenotype and review of the literature

Abstract

Trisomy 22 is commonly found among spontaneous abortions, second in frequency of occurrence only to trisomy 16. Most earlier reports of surviving trisomy 22 cases in the literature are thought to represent the product of unbalanced 11;22 translocations or the result of undetected mosaicism, since this condition is thought to manifest early embryonic or fetal lethality. We present two strikingly similar cases of non-mosaic trisomy 22 surviving to late gestation. In this paper we emphasize the unique phenotype of this trisomy which included intrauterine growth retardation, microcephaly, broad flat nasal bridge with epicanthal folds and ocular hypertelorism, microtia, variable cleft palate, webbed neck, congenital heart defects involving anomalous great vessels, anorectal and renal anomalies, and hypoplastic distal digits with thumb anomalies. We also explore why some cases survive to late gestation. Confined placental mosaicism, a frequent finding in other lethal trisomies, has been ruled out in one of the cases. Molecular studies done to assess the parental origin of the extra chromosome in the other case showed that the non-disjunction originated during maternal meiosis II. Parental origin of the extra chromosome does not seem to play a role in late survival for trisomy 22.

Second‐Trimester Sonographic Findings in Trisomy 22

“…5,6 Only recently have high-resolution cytogenetics and fluorescence in situ hybridization techniques made the characterization of this condition possible, allowing the trisomy 22 phenotype to be delineated clearly. 7,8 Well-known features associated with this condition include fetal growth restriction in association with structural anomalies involving mainly the heart, face, kidneys, and gastrointestinal tract. 3 Most of these anomalies can be readily detected prenatally by sonography.…”

“…However, according to a MEDLINE search, the secondtrimester sonographic diagnosis of trisomy 22 had been reported only once in a fetus with fetal growth restriction and multiple structural anomalies, including congenital heart defects, bilateral cleft lip and palate, absent stomach bubble, shortened big toe, short femurs, and unilateral renal agenesis. 9 There have been at least 3 other reports describing prenatal diagnosis in the third trimester 7,10,11 ; however, only lim- …”

“…In the first of these reports, 7 the detection of microcephaly, congenital heart defects, and ambiguous genitalia led to the prenatal diagnosis of trisomy 22 by amniocentesis and termination of pregnancy at 31 weeks. In the second, 10 the patient had an initial second-trimester scan at 18 weeks that showed the fetus to be 2 weeks' size less than "certain menstrual weeks."…”

“…12 The pathogenesis in these cases may involve a number of mechanisms depending on the type of chromosomal aberration and coexistent structural anomalies. Although congenital heart defects are observed in more than 90% of fetuses with trisomy 22, 7,8 hydrops fetalis can be mediated by distinct mechanisms and may be attributed only in part to structural or functional defects of the heart. Indeed, in 1 of our fetuses with hydrops fetalis, there was no cardiac defect evident on prenatal sonography.…”

Confirmation of mosaic trisomy 22 in an infant with failure to thrive

“…They include constant features such as mental retardation, growth retardation, microcephaly, cryptorchidism (males), very frequent (>80%) features such as muscle underdevelopment/ hypotonia, micrognathia, cleft palate, large low-set malformed ears, pre-auricular tags and/or sinuses, long slender fingers and/or finger-like thumbs, congenital heart disease, congenital hip dislocation and frequent (>60%) features such as craniofacial asymmetry, long and beaked nose, long philtrum and strabismus 6,7 . Described clinical manifestations include microcephaly, hypertelorism, epicanthic folds, hypoplastic or low set ears, mid-face hypoplasia, hypoplastic distal phalanges, abnormalities of male genitalia, pre and postnatal growth retardation, cleft palate, cardiac and/or renal anomalies and anal atresia/stenosis 8 . This case did not have the major anal, ear or eye malformations [especially the 'cat eye' sign caused by iris coloboma] that are classically associated with this syndrome.…”