First report of a patient with a mixoploidy 47,XXX/94,XXXXXX.

Summary: First report of a patient with a mixoploidy 47,XXX / 94,XXXXXX: We present a 16 years old female with a chromosomal mixoploidy and multiple phenotypic anomalies. Peripheral blood G-band karyotype was 47,XXX and her skin fibroblast karyotype revealed a mosaic with a 47,XXX cell line in 88% of metaphases and a 94,XXXXXX cell line in 12% of metaphases, consistent with a hypertetraploidy. The most prominent clinical signs were: short stature, left upper limb asymmetry, senile-like appearance, generalized hypertrichosis, and small hands and feet. Radiological examination showed bone dysplasia. The result of molecular studies demonstrated that the patient inherited the two X chromosomes from the mother and one from the father, indicating that her 47,XXX trisomy resulted from an oogenesis error in the first meiotic division. The 94,XXXXXX cell line was likely the result of a cytokinesis error. To our knowledge, this is the first documented patient with a trisomy and a hypertetraploidy. Key words: Mixoploidy - Hypertetraploidy - Trisomy - Mosaicism - Bone dysplasia. INTRODUCTION In mixoploidy the cells of an individual display two or more genetically different chromosome patterns, which could be due to mosaicism or chimerism. One of the cell lines usually carries a diploid chromosome number whereas the other exhibits multiples of a normal number of chromosomes e.g, three or four sets of haploid chromosomes. We present a female carrier of a trisomy (47,XXX) and of another cell line consistent with a hypertetraploidy (94,XXXXXX). CASE REPORT We report a female patient aged 16, bora of young and healthy parents, bom after an apparently normal pregnancy and delivery at 40 weeks (weight was 1,800 g, and height 32 cm). She began to utter her first words at the age of one and she began to walk when she was three. Physical examination at the age of 16 showed a senile-like appearance (Fig. 1A), generalized hypertrichosis, hoarse voice with some deficient motor co-ordination and growth retardation [weight 34.5 kg (-4 SD), height 126.7 cm (-7 SD), body mass index 21.6 (+1SD), cephalic circumference 51 cm (-2.8 SD)]. Her IQ performance was 71 (WISC-R test). A shorter and asymmetric left upper limb was noted (Fig 1D). She exhibited short palpebral fissures, moderate strabismus, small ears with hypoplastic lobules, a smooth philtrum, thin lips, a discrete trismus and prognathism. Oligodontia and abnormally shaped teeth were also present. She had a short and broad neck, a narrow thorax and narrow shoulders, mild scoliosis and marked lumbo-sacral hyperlordosis. She displayed a limited flexibility of hands with hypoplasia of the thenar and hypothenar areas. Camptodactyly and syndactyly of the 4th and 5th fingers of both hands were observed (Fig. 1B). The feet and toes were small (Fig. 1C). The radiological findings include a narrow thorax (Fig. 2A). Scoliosis with tall vertebral bodies with a reduction of the intervertebral spaces and a diminished antero-posterior diameter (Fig. 2D). Small iliac bones, coxa valga, short femoral necks, thin pubic branches (Fig. 2B) and thin large bones were also observed. Hand radiology showed a small carpus, absence of the pisiform and lunate bones, radial deviation of the metacarpals. Short and thin metacarpal and phalangeal bones, and clinodactyly (Fig. 2C). G-band karyotype on peripheral blood was 47,XXX (Fig. 3A). Skin biopsy fibroblast karyotype revealed a mosaic with a 47,XXX cell line (Fig. 3B) in 88% of metaphases and a 94,XXXXXX cell line (Fig. 3C) in 12% of 50 metaphases. DNA was extracted from peripheral lymphocytes by standard methods was analyzed employing several markers of the X-chromosome including the DMD, the haemophilia B regions as previously described (9). The results indicated that two X-chromosomes were inherited from the mother and a third from the father (Fig. 4). DISCUSSION We present a case of mixoploidy 47,XXX/94,XXXXXX in a 16 year old female with multiple phenotypic abnormalities. …