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FINAL DIAGNOSIS:
Karyotype: 46,XY.ish der(7)t(7;16)(p22.3;p13.3)(7ptel+, 7wcp+,16ptel+,16wcp+)
Male Karyotype with a Cryptic Unbalanced Sub telomeric Rearrangement between Chromosomes 7 and 16 by FISH Resulting in Partial Trisomy for a Small Region of Chromosome 16p
CGH: 16p 13.3 (CTD- 3077j14->CTD-3149P1) x3.
A signal copy gain of 21 BAC clones at the subtelomereric region of the short arm of chromosome 16 at 16p 13.3, which is approximately 3.9 Mb in size is noted. No significant material is lost from the p arm of chromosome 7. Fig. 7
DISCUSSION:
This patient inherited this rearrangement through his mother and maternal karyotype showed: 46,XX,t(7;16)(p22.3;p13.3), female with balanced translocation carrier involving a subtelomeric rearrangement between chromosome 7 and 16, Figs. 8 and 9. The maternal uncle has the same genetic disorder as the baby suggesting the presence of the rearrangement in one of the grandparents.
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Uncle phenotype includes mental retardation, hearing loss, delayed growth, cleft palate, brain anomalies, optic nerve hypoplasia, genitourinary abnormalities, and dysmorphic features including low set ears and microganthia. Figs. 10 and 11
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Unbalanced submicroscopic telomere rearrangements are a significant cause of idiopathic mental retardation with or without congenital malformations, accounting for approximately 5% of these cases. Subtelomeric regions are the most gene rich regions. The most common clinically significant subtelomeric imbalances found in a study of 11688 cases by Ravnan et al were Del 1p,22q,4p,9q,8p,2q, and 20p, and the most common familial variants were a deletion or duplication of 10q, deletion of 4q, deletion of Yq, and duplication of X/Yp onto Xq.
Complete trisomy 16 is the most frequent autosomal anomaly resulting in spontaneous miscarriage. Partial trisomy 16p is rare. More than 30 cases of partial subtelomeric trisomy 16p have now been described and the majority of cases are secondary to familial balanced translocation. The phenotypic consequences may be dependent on the size of the imbalance and the gene content of the region. The pattern of malformations and anomalies in the patients is strikingly similar.
This syndrome is associated with developmental delay, recurrent respiratory infections, seizures, congenital heart defect, renal and genitourinary anomalies, and cleft palate. Characteristic facial features include scant hair, micrognathia, hypertelorism, upward slanting palpebral fissures, low set ears, a long Philtrum and thin upper lip, overlapping fingers, and an abnormally placed thumb.
However, not all subtelomeric imbalances result in a phenotype and that the lack of phenotypic effect may be related to the size of the rearrangement or the involvement of region of the genome that are tolerant to dosage imbalance. Further studies may reveal more information about these kinds of genetic disorders and may help to identify more familial variants,
Acknowledgment: Carol Minyon (Sr. Cytogenetic Technologist)
REFERENCES:
Contributed by Amer Heide, MD and Urvashi Surti, PhD
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