The Principles of Clinical Cytogenetics - Extra Materials - Springer

Autosomal Aneuploidy 147
trisomies, the presence of an undetected, normal cell line confined to certain tissues cannot be
excluded, as pointed out by Robinson and Kalousek (130).
The most consistent phenotypic abnormalities include intrauterine growth retardation, low-set ears
(frequently associated with microtia of varying degrees plus tags/pits), and midfacial hypoplasia.
Other frequently seen abnormalities are microcephaly, hypertelorism with epicanthal folds, cleft palate,
micrognathia, webbed neck, hypoplastic nails, anal atresia/stenosis, and hypoplastic genitalia.
Cardiac defects, complex in some cases, are seen in 80% of patients. Renal hypoplasia/dysplasia are
also common. Skin hypopigmentation (hypomelanosis of Ito) is usually present in mosaic cases.
Most nonmosaic patients die in the first months of life. The longest survival reported is 3 years (131).
That patient had severe growth and developmental delay and died a few days before his third birthday.
Prolonged survival to over 20 years has been observed in mosaic patients.
Trisomy 22 cells can be detected in both blood lymphocytes and skin fibroblasts. The risk for
recurrence is unknown.
Other Rare Autosomal Trisomies
As noted in the Introduction, mosaic or nonmosaic autosomal trisomies for chromosomes other
than 1 and 11 have been reported in liveborns. Trisomies are detected much more frequently in spontaneous
abortuses or in prenatal diagnostic specimens, following which elective terminations are
often performed. Thus, the occurrence of such trisomies in liveborns is extremely rare and only isolated
case reports are available. The risks for recurrence for these rare trisomies are probably negligible.
The following discussion will include cytogenetically confirmed postnatal cases only.
A single case of liveborn mosaic trisomy 2 has been reported (132). The mosaicism was detected
in amniocytes and confirmed postnatally in liver biopsy fibroblasts (4 of 100 cells) but not in blood,
skin fibroblasts, or ascites fluid cells. At 16 months of age, the child had hypotonia, microcephaly,
and growth and developmental delay. Another case of possible mosaic trisomy 2, detected at amniocentesis
and observed in a single cell of a foreskin fibroblast culture following the birth of a
dysmorphic child, was reported in an abstract (133). Three cases of mosaic trisomy 3 have been
reported (10,134,135); one of these, a severely mentally retarded woman, was alive at age 32. Clinical
features in the three cases vary, except all had prominent forehead, ear and eye anomalies. One
case each of postnatally confirmed mosaic trisomy 4 (136) and mosaic trisomy 5 (137) has been
reported. In both cases, the trisomic cells were detected in prenatal amniocytes and confirmed postnatally
in skin fibroblasts, but not in blood lymphocytes. Both patients had multiple congenital anomalies.
One case of mosaic trisomy 6 has recently been reported (138). This child was born at 25 weeks
of gestation. Clinical features included heart defects (ASD and peripheral pulmonary stenosis), large
ears, cleft right hand, cutaneous syndactyly, overlapping toes of irregular shape and length, and epidermal
nevi. Growth was considerably delayed, but development was relatively normal at age 2.
Trisomy 6 cells were detected in skin fibroblasts but not in blood. At lease six cases of cytogenetically
documented mosaic trisomy 7 in skin fibroblasts have been recorded (reviewed in ref. 139,
140,141). All patients were phenotypically abnormal. Common features included growth and developmental
delay, skin pigmentary dysplasia with hypopigmentation and hyperpigmentation, facial or
body asymmetry, and facial dysmorphism. One mentally retarded male was 18 years old at time of
report. A few cases of liveborn mosaic trisomy 10 have been reported (reviewed in ref. 142,143). One
patient was mosaic for trisomy 10 and monosomy X in skin fibroblasts, whereas only monosomy X
cells were present in blood. This infant died at 7 weeks of age from heart failure. The common
clinical phenotype included growth failure, craniofacial dysmorphism (prominent forehead,
hypertelorism, upslanted palpebral fissures, blepharophimosis, dysplastic large ears, retrognathia),
long slender trunk, deep palmar and plantar fissures, cardiac defects, and short survival.
At least six cases of trisomy 12 have been reported in liveborns; all were mosaics (144–148). The
earliest reported case was that of an infertile man, whereas the most recent case involved an infant