Further phenotypic delineation of subtelomeric (terminal) 4q deletion with emphasis on intracranial and reproductive anatomy

Abstract

Objective: 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.

Results: 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.

Conclusion: 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.

Figure 1

Peripheral GTG banded metaphase karyotype for 46,XX del(4)(q32) proband indicating region of deleted chromosome 4 (arrow).

Figure 2

Fluorescent in situ hybridization study indicating deletion of distal long arm of chromosome 4. (Green = 4p, Red = 4q [unpaired signal]; chromosome 21 = control).

Figure 3

Vesicle-like punctations (arrow) observed on serosa of R fallopian tube (RF). RO = right ovary.

Figure 4

Fibroadipose nodule (arrow) interposed between right round ligament (RR) and right Fallopian tube (RF). U = uterus, RO = right ovary.

Figure 5

Brain MR demonstrating asymmetric density (arrow) at the inferior margin of L globus pallidus in 46,XX del(4)(q32).

Figure 6

Left hand radiograph showing characteristic abnormal fifth distal phalanx (arrow) in 46,XX del(4)(q32). The defect was bilateral.