PMC3905920_01
Representative photographs of the patient at 3 days of age (a-c) and 2 months of age (d-e), respectively. (a-b) The main facial features of the 3-day-old female newborn were narrow palpebral fissures, microretrognathia, hypertelorism with slight upslanting of her palpebral fissures, low-set, dysplastic ears with folded upper helices, a round face and a small nose with an almost absent nasal bridge. (c) The external genitalia were dysplastic. A sandal gap was present between the first and second toe. (d) The thumbs were hypoplastic and proximally placed. (e) The second and fifth fingers were outstretched and deviated towards the middle fingers; a clinodactyly of the distal phalanges could be observed.
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F1
At three days of age, the patient's facial appearance (Figure 1a-b) was characterized by narrow palpebral fissures, hypertelorism with slight upslanting of her palpebral fissures (Figure 1a), microretrognathia (Figure 1a-b), dysplastic, low-set ears with folded upper helices (Figure 1b), a small nose and a round face (Figure 1a-b). Her neck was short with an excess of skin (Figure 1a-b). Her outer genitals were ambiguous with dysplastic labia (Figure 1c), and she had a mild sacral meningocele. Severe abnormalities of both hands could be observed, including proximally placed hypoplastic thumbs (Figure 1d) and a deviation of her second and fifth fingers towards the middle fingers (Figure 1e). Her second and fourth fingers were always outstretched, and her distal phalanges showed clinodactyly (Figure 1d-e). Sandal gaps were noted between her first and second toes (Figure 1c).
aCGH and FISH analysis of chromosome 16 in our patient. (a) aCGH identified a duplication of chromosome region 16pter-p11.2 Log 2 ratio data for two dye-swap plots (patient/control) are presented according to their positions in the human genome. The black line indicates the moving average. The greenish shaded region indicates the duplication on chromosome region 16pter-p11.2. The blue horizontal line marks the location of the centromere. (b) Representative image of chromosome metaphase demonstrating hybridization of the subtelomeric probe 16pter (red) in the FISH analysis. The white arrow indicates the location of the additional chromosomal region 16pter-p11.2 translocated onto the telomeric region of chromosome 6p.
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F2
Because cytogenetic analysis alone could not identify the origin of this chromosomal region, aCGH was performed, which demonstrated duplication of the entire short arm of chromosome 16 (16pter to 16p11.2) with a size of approximately 33.83 Mb (Figure 2a) involving positions 119.664 to 33.923.140. To confirm these results, FISH analysis using a subtelomeric probe for chromosome 16p was performed on metaphase spreads of the patient's lymphocytes (Figure 2b). In addition to the two normal hybridization signals detected on chromosomes 16p, an extra hybridization signal was detected on the p-telomere of the structurally abnormal chromosome 6 (Figure 2b).