Further phenotypic delineation of subtelomeric (terminal) 4q deletion with emphasis on intracranial and reproductive anatomy
Eric Scott Sills1, MJ Burns2 , Laurinda D Parker2, Lisa P Carroll2, Lisa L Kephart2, CS Dyer2, Peter R Papenhausen3 and Jessica G Davis4
1Reproductive Medicine Associates at Vassar Brothers, Fishkill, New York, USA
2Murphy Women’s Center, Murphy, North Carolina, USA
3Cytogenetics Laboratory, Laboratory Corporation of America, Research Triangle Park, North Carolina, USA
4Division of Human Genetics, Department of Pediatrics, Weill Medical College, Cornell University, New York, New York, USA
To describe selected morphological and developmental features associated with subtelomeric deletion at chromosome 4q.
Materials and methods
A 21-year old female was brought for gynecologic evaluation of menorrhagia. High-resolution metaphase karyotype and subtelomere fluorescent in-situ hybridization (FISH) analysis were used for genotype determination. Pelvic anatomy was characterized via CT and laparoscopy; MR and CT were used for intracranial imaging.
A de novo deletion [46,XX del(4)(q32)] was identified cytogenetically and confirmed as a terminal loss via subtelomere FISH. Hand/foot malformation characteristic of deletion at this segment was present. Pelvic CT and laparoscopy revealed normal uterine anatomy. Fallopian tubes appeared grossly unremarkable, and a right ovarian cyst was excised without difficulty. Bilateral broad ligament fibroadipose nodularities were noted adjacent to the uterus between round ligament and fallopian tube. Neurological exam revealed no focal defects, although brain MR identified an abnormal signal intensity at the inferior margin of the globus pallidus, consistent with old lacunar infarct and gliosis. Developmental delay was supported by an observed level of general intellectual function estimated at age seven.
Terminal deletion of the long arm of chromosome 4 is a rare genetic event associated with a distinctive phenotype dependent on the size of the deletion. Chromosomal losses that span the 4q32 band include mental retardation and mild craniofacial anomalies. Here, further characterization of this disorder is offered including precise quantification of the DNA loss, information on brain morphology and pelvic anatomy. Additional studies will be required to characterize the full developmental and physiologic implications of this unusual genetic disorder.
Orphanet Journal of Rare Diseases 2007, 2:9. Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0).
The incidence of terminal deletion of chromosome 4q is believed to be very low but is not known with certainty. Indeed only a limited number of reports describing such deletions exist  and very few of these have specifically addressed reproductive and intracranial morphology in affected individuals. Here we present an analysis of the impact of this unusual autosomal deletion on pelvic and brain anatomy.