Abstract Ref Number = APCP849
46,XY DISORDER OF SEX DEVELOPMENT AND 9p- SYNDROME
Hannie Dewi Hadyani Kartapradja,Chrysantine Paramayuda,Debby Dwi Ambarwati,Alida Roswita Harahap,Nanis Sacharina Marzuki
Eijkman Institute for Molecular Biology
Background : Partial monosomy of short arm of chromosome 9 is a rare disorder which up to know there were only few (98) cases reported in the literatures. This condition characterized by trigonocephaly, mental retardation, low-set and/or malformed ears, and facial dysmorphic. Abnormal genitalia and hypopigmentation can also be found in some patients. DMRT1 (Doublesex- and mab-3-related transcription factor 1) gene plays important roles in the male genitalia formation. Loss one copy of this gene may occur simultaneously with 9p-, since it located at the 9p24.3 region and will lead to undermasculinized male. This study presents 5 cases (3 ‘girls’ and 2 boys) with 9p- syndrome with clinical spectrum of disorder of sex development (DSD).
Case Presentation Summary : Three patients were referred for chromosomal assessment due to variable degree of genitalia ambiguity, such as non palpable testes, suspected CAH (congenital adrenal hyperplasia), or presence of vagina and penis. A five-year old girl presenting with short stature, cubitus valgus, and clynodactily was referred due to clinical suspicion of Turner syndrome. All cases showed 46,XY karyotype results with 9p- in different regions. One patient showed monosomy 9 and ring 9 mosaicism karyotype. Further molecular analysis using metaphase FISH (Fluorescent In Situ Hybridization) on this patient revealed loss one copy of DMRT1 gene, which was confirmed by CGH microarray.
Learning Points/Discussion : In 9p- syndrome, loss of DMRT1 gene should be considered. Since this gene plays important role in male sex development, DMRT1 gene haploinsufficiency may results in 46,XY DSD phenotypes with variable degree of undermasculinisation. The loss of DMRT1 may be detected by FISH.
Keywords: 9p- DMRT1 gene XY sex reversal 46XY DSD