The Principles of Clinical Cytogenetics - Extra Materials - Springer

148 Jin-Chen Wang
with multiple malformations and pigmentary dysplasia who died at 2 monts of age. Phenotypic presentation
was variable and included facial dysmorphism, scoliosis, ASD, PDA, dysplastic pulmonary
and tricuspid valves, short stature, and mental retardation. Trisomy 12 cells have been found in lymphocytes,
skin fibroblasts, urine sediments, and internal organs including liver, spleen, adrenal, and
thymus.
At least 15 cases of mosaic trisomy 14 have been reported in liveborns (reviewed in ref. 149,150).
The most consistent phenotypic abnormalities were growth and mental retardation, broad nose, lowset
dysplastic ears, micrognathia, congenital heart defects, and micropenis/cryptorchidism in males.
One prenatally diagnosed patient had alobar holoprosencephaly and died at 36 days of age (150).
Survival varied from days to more than 29 years. Trisomy 14 cells were detected in both lymphocytes
and fibroblasts, with a generally higher percentage in lymphocytes. There was no clear correlation
between the proportion of trisomic cells and the severity of the phenotype. In patients with body
asymmetry, trisomic cells were usually limited to the atrophic side.
At least ten cases of liveborn trisomy 15 have been recorded (reviewed in refs. 151 and
154;153,154), two of them were reportedly nonmosaics (155,156). In some cases, the trisomy 15 cell
line was present only in skin fibroblasts and not in peripheral blood lymphocytes. The concurrent
finding of maternal uniparental disomy 15 (see Chapter 19) in the normal cell line was reported in
two of the cases (152,154). These cases appeared to have the most severe phenotype. Phenotypic
abnormalities include hypotonia, various craniofacial dysmorphisms, minor skeletal anomalies, congenital
heart defects, and short survival.
Two cases of confirmed mosaic trisomy 17 have been reported (157,158). The trisomic cells were
not seen in lymphocytes, but were found in high percentage in skin fibroblasts. One patient, age 8 years
at the time of reporting, had mental and growth retardation, microcephaly, minor dysmorphism, seizures,
hearing loss, attention deficit hyperactivity disorder, and autistic behavior. The other patient
had mild dysmorphic features and moderate neurological involvement that the authors suggested
could be related to prematurity. Two cases of mosaic trisomy 19 are in the literature, one of them was
a stillborn male and the other died on day 13. Clinical features were varied and included facial
dysmorphism with no report of major malformation (159,160).
AUTOSOMAL MONOSOMIES
As noted in the Introduction, autosomal monosomies are extremely rare in either liveborns or abortuses,
reflecting the severity of the genetic imbalance resulting from the loss of an entire chromosome.
The only monosomies that have been reported are monosomy 21, mosaic monosomy 22, and a single
case reported in an abstract of a possible mosaic monosomy 20 in a 3 1/2 year old boy with atypical speech/
language delay, behavior problems, microcephaly, and patchy hypopigmentation of the skin (161).
Monosomy 21
Mosaic monosomy 21 was reported in four liveborns in the early literature (162–165). The most
prominent features included intrauterine growth retardation, postnatal growth and mental retardation,
hypertonia, facial dysmorphism with downward slanting palpebral fissures, large low-set ears, and
micrognathia. A more recent report described pathological findings of an electively terminated
20-week female fetus after mosaic monosomy 21 was diagnosed by repeated amniocenteses (166).
The above-described facial abnormalities were present in this abortus. In addition, a complex cardiac
malformation, malrotation of the bowel, uterus didelphys, small dysmature ovaries, and focal cystic
dysplasia of the lung were noted.
Approximately ten cases of apparently nonmosaic monosomy 21 have been reported in liveborns
(reviewed in ref. 167,168,169). Some of these cases have subsequently been shown to represent
partial monosomy 21 resulting from an undetected subtle translocation (170), explaining the observation
that mosaic monosomy 21 is less commonly observed than apparently nonmosaic monosomy