Further phenotypic delineation of subtelomeric (terminal) 4q deletion with emphasis on intracranial and reproductive anatomy.
OBJECTIVE
To describe selected morphological and developmental features associated with subtelomeric deletion at chromosome 4q.


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.


CONCLUSIONS
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.
Sills
Eric Scott
ES
Reproductive Medicine Associates at Vassar Brothers, Fishkill, New York, USA. esills@rmavb.com.
Burns
M J
MJ
Parker
Laurinda D
LD
Carroll
Lisa P
LP
Kephart
Lisa L
LL
Dyer
C S
CS
Papenhausen
Peter R
PR
Davis
Jessica G
JG
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4; D019465:Craniofacial Abnormalities / Q000235:genetics; D002658:Developmental Disabilities / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000379:methods; D005836:Genitalia, Female / Q000473:pathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008595:Menorrhagia / Q000209:etiology / Q000473:pathology; D010641:Phenotype; D016615:Telomere