SAT-285 Role of chromosome microarray in identifying a genetic cause of undervirilized external genitalia and growth delay in an infant: 6p Duplication associated with short stature and micropenis

Document Type



Paediatrics and Child Health


THE CASE 4 mo M born at term 7lbs 7.5oz, 19.5 inches via C-section, referred for micropenis found during evaluation for circumcision. No history of hypoglycemia. Of note, dad is s/p hypospadias repair and is short at 5th %ile. PE showed short stature, length at 3rd %ile (-1.91 SDS), wt 53rd %ile, HC 76th %ile. Stretched penile length 1.5 cm (-2.5 SDS = 1.9cm), testes 1.5 cm each, normal. Periorbital hemangioma noted. Otherwise normal exam. Chromosome microarray showed a 6.1 Mb duplication of the terminal region of 6p, pathogenic; and a 222 kb deletion of terminal 17p (felt to have no clinical significance). Patient referred to Genetics. Parental testing showed balanced translocation in dad's chromosome 46,XY,t(6;17)(p25.1;p13.1)]. GH, TSH, FT4, LH, FSH, AMH levels normal. Total Testosterone 68 ng/dL. CAH-6 panel within expected limits. Testosterone therapy 50mg/mo x 3mos initiated to improve penile length.
Discussion: Workup of underlying cause of male undervirilization is challenging. More often than not, a definitive diagnosis remains elusive. The current case underlines the invaluable contribution of chromosomal microarray in this endeavor. Duplication of distal fragment of chromosome 6p is extremely rare, with region, and as expected, case reports thus far have a wide phenotypic variability. Common features include pre-/postnatal growth delay, developmental disability, congenital malformations of the heart, kidneys, eyes. However to our knowledge, this is the first report of a patient with 6p25pter with micropenis. Of note, a patient with 6p25pter + 22q11.2pter trisomies was reported to have penile chordee and cryptorchidism (Scarborough, et al, 1986). Patienit's dad has history of hypospadias as well, suggesting a correlation between this specific mutation and undervirilized male external genitalia. Review of 26 OMIM genes contained in the reported abnormal region showed scant known data about these genes. However, gene transcripts from 5 of these OMIM genes (DUSP22, FAM50B, HUS1B, FOXQ1, SERPINB9) were shown to be highly expressed in the testis +/- brain in humans/animals, suggesting a possible role that these genes play in male genital development.
Conclusion: A genetic cause of micropenis is often hard to establish. We report a case associated with a pathogenic duplication of the terminal region of 6p chromosome. To our knowledge, no such case has been previously reported. This rare chromosome abnormality does have other associated medical complications for which he needs to be monitored. The crucial role of chromosome microarray in picking up such abnormalities in workup of undevirilization is emphasized. More research is needed to elucidate the mechanism by which the affected genes influence male genital development.


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Publication (Name of Journal)

Journal of the Endocrine Society