The Principles of Clinical Cytogenetics - Extra Materials - Springer

152 Jin-Chen Wang
and head circumference were normal at birth. The most frequently observed phenotypic features
include mental retardation, speech and motor delay, dilatation of cerebral ventricles, mild facial
dysmorphism (depressed nasal bridge, short nose, upturned nares, low-set and posteriorly rotated
ears), and vertebral abnormalities. Agenesis of the corpus callosum was noted in six patients and
cardiac defects in five. Deep palmar and plantar creases have also been reported. The phenotype
resembles, to some degree, that of mosaic trisomy 8.
Tetrasomy 9p
Tetrasomy 9p [47,XX or XY,+i(9)(p10)], resulting from the presence of a supernumerary isochromosome,
has been reported in more than 20 liveborns (reviewed in ref. 210,211–213). The isochromosome
consists of either the entire short arm of chromosome 9 as described above, the entire short arm
and part of the heterochromatic region of the long arm, or the entire short arm and part of the long arm
extending to the euchromatic region. No consistent phenotypic differences have been observed among
the three types. Both mosaic and apparently nonmosaic patients have been reported. The tetrasomy 9p
cells were seen in both lymphocytes and skin fibroblasts. In contrast to tetrasomy 12p (described later),
the 9p isochromosomes were present only in lymphocytes in five patients (210,211,214,215) and in
fibroblasts at a much lower percentage than in lymphocytes in two others (216,217). The mechanism for
this observed tissue-limited mosaicism for different chromosomes is not clear.
Survival is variable, ranging from a few hours to beyond 10 years. The most frequent phenotypic
abnormalities include low birth weight, growth and developmental delay, craniofacial anomalies
(microphthalmia, low-set malformed ears, bulbous tip of the nose, cleft lip/palate, micrognathia),
short neck, skeletal anomalies, joint contracture, nail hypoplasia, and urogenital anomalies. Cardiac
defects are present in over 50% of patients. Overall, nonmosaic patients are more severely affected.
One patient who had the i(9p) present in 75% of lymphocytes but not in skin fibroblasts had only
mild developmental delay and minor anomalies (210).
Tetrasomy 12p
Tetrasomy 12p (Pallister–Killian syndrome) results from the presence of a supernumerary isochromosome
for the entire short arm of chromosome 12 [i(12)(p10) or i(12p)] (see Fig. 10). The syndrome
was first described in 1977 by Pallister et al. in two adults, a 37-year-old man and a 19-year-old
woman (218). In 1981, Killian and Teschler-Nicola reported a 3-year-old girl with similar clinical
manifestations (219). Subsequently, more than 60 cases have been reported (reviewed in ref. 220,
221), and many more have been observed but not reported in the literature. All cases were mosaics,
with a normal cell line in addition to cells containing i(12p). Maternal age for reported cases has been
shown to be significantly higher than that for the general population (222). This observation has been
taken to suggest that the isochromosome arises from a meiotic error and that the normal cell line
results from subsequent loss of the i(12p) from some cells. In six of seven cases studied by molecular
analysis, the meiotic error was determined to be maternal (223,224). Tissue specificity and both the
in vivo and in vitro age dependencies of the i(12p) have been well demonstrated (reviewed in ref. 225).
The i(12p) is found in a high percentage of skin fibroblasts and amniocytes, but it is rarely seen in
blood lymphocytes. The percentage of cells containing the isochromosome also decreases with age.
The presence of tetrasomy 12p in 100% of bone marrow cells has been reported in at least two
newborn infants (226,227) and in only 6% of marrow cells in a 3-year-old child (228). In lymphocytes,
it has been found in fetal blood (225,229), but has never been seen beyond childhood. In a case
reported by Ward et al., the i(12p) was present in 10% of lymphocytes initially, but was not seen in
these cells when the patient was 2 months old (226). The isochromosome is more stable in skin
fibroblasts and can be found in adults, usually at a lower percentage than in younger patients. When
fibroblast cultures were examined, the percentage of cells containing the isochromosome decreased
with increasing numbers of cell passages (223,225–227,230). One study using FISH showed that in
lymphocytes, the i(12p) was present in a significantly higher proportion of interphase nuclei than in