Congenital Asymmetry and Diploid-Triploid Mosaicism

Abstract

A 9\m=1/2\-year-oldgirl with congenital asymmetry manifested by a larger right half of the body demonstrated diploid-triploid mosaicism of chromosomes from skin fibroblast cultures but normal leukocyte karyotypes. Mosaicism was found in cells from both the larger and smaller sides of her body. The association of congenital asymmetry and diploid-triploid mosaicism has been reported only twice but may be more common than previously recognized.Congeni tal asymmetry as a rec¬ ognizable clinical problem ap¬ pears to be rare. The term congenital asymmetry is preferable to either "hemihypertrophy" or "hemiatrophy," since there is usually no evidence of excessive growth on ei¬ ther side. Even the larger side is of¬ ten below average for chronologic age. Congenital asymmetry is fre¬ quently associated with anomalies of one or more organ systems, particu¬ larly the neurocutaneous and skeletal structures. Retroperitoneal tumors of the adrenal glands and kidneys are more frequent in these patients.17 Moreover, in 1953 Silver et als de¬ scribed a syndrome of congenital asymmetry, short stature, and pre¬ maturely elevated urinary gonadotrophin values in children. Silver's syndrome is now an established en¬ tity and was the subject of an exten¬ sive review in 1964.9 A 9V2-year-old girl with congenital asymmetry demonstrated a normal chromosome karyotype in peripheral blood lymphocytes and diploid (2n)-triploid (3n) chromosomal mosaicism in skin fibroblasts. To our knowledge 2n/3n chromosomal mosaicism in this condition has been reported only twice previously.10"11 Report of a Case This 9y2-year-old girl was admitted to the pediatrie service for a diagnostic eval¬ uation of congenital asymmetry, most no¬ ticeable in the face and extremities with the right side larger than the left (Fig 1). She was the product of an uncomplicated 36-week gestation and weighed 1,588 gm (3 lb 8 oz) at birth. A younger sibling was reportedly normal.The mother also had three children dur¬ ing a previous marriage, all of whom were said to have been normal physically and of superior intelligence. The mother and father were not available for chromosomal studies or blood typing. Our patient did not walk until 2 years of age, nor talk distinctly until age 5 years.On physical examination the weight was 29 kg (64 lb), height, 124 cm (49 in), and head circumference, 49.5 cm. The face appeared smaller on the left, the right side of the tongue being noticeably larger than the left. (Table 1).Additional physical findings included noticeable down-turning of the outer edges of the mouth (Fig 1, left), a soft systolic functional murmur at the third left interspace, and infantile sexual devel¬ opment. No breast tissue was palpable and the external genitalia appeared com¬ patible with her chronologic age. There was moderate thoracic scoliosis to the right which was confirmed by chest roentgenogram. The liver and spleen were not palpable. No abdominal masses were de¬ tected. There was clinodactyly with a single crease on the left fifth digit. The skin appeared normal...

Mixoploidy in humans: Two surviving cases of diploid‐tetraploid mixoploidy and comparison with diploid‐triploid mixoploidy

“…In (2n/3n) mixoploidy, the abnormal cell line has 69 chromosomes, whereas in (2d4n) mixoploidy the chromosome complement of the abnormal line is 92. We review the literature on 2d4n mixoploidy and report 2 female long-term survivors who had mental retardation and minor anomalies, some being similar to those reported in 2d3n mixoploidy [Ferrier et al, 1964;Donnai et al, 1986;Jenkins et al, 1971;Graham et al, 1981;Tharapel et al, 1983;Wulfsberg et al, 19911. These anomalies include severe intellectual handicap, digital anomalies, reduced peripheral limb muscle bulk, growth asymmetry, truncal obesity, and skin pigmentary dysplasia.…”

Monozygotic twins discordant for the Russell‐Silver syndrome

“…He found normal 46,XX chromosomes. Jenkins et al [1971] reported an association between congenital asymmetry and chromosomal mosaicism, but no cause-effect relationship has been established, and this association is not limited to RSS patients. The other possibility for mosaicism would be a point mutation which occurred after the splitting of the zygote into twins.…”

Multiple Pregnancies

“…The fi nding of diploid/triploid chimeras (e.g., Van den Berghe and Verresen 1970 ) was taken as evidence that fertilization of a large polar body (common in mice) produced such abnormal individuals (dispermic chimeras). Other proposed mechanisms, such as secondary nondisjunction of whole haploid sets (Jenkins et al 1971 ) , are much less likely. De la Chapelle et al ( 1974 ) have suggested, as did other investigators, that early fusion of two embryos may be the way that whole-body chimeras are produced spontaneously, much as in the experimental model.…”