High Variability of Sexual Ambiguity and Clinical Expression in two Patients with a 46,XY del(9p) Kariotype

We report the clinical features of two children (case 2 underlined) with 46XY,del(9p) karyotype and different clinical expressions of the disease. Case 1 - uncomplicated pregnancy with normal delivery of a 2580g/48cm male newborn at term with mid-penis hypospadias and microphallus, biphid scrotum, inguinal cryptorchidism; Case 2 – uncomplicated pregnancy with caesarean delivery due to foetal inertia of a 3750g/49cm female newborn at term with sex reverse/normal female genitalia. Shared dysmorphic features: brachicephalia, epicanthic folds,prominent nasal root, broad chest, theletelia, hypotonia. Differential features: - Asymmetrical face, microcephaly, hypothelorism, bilateral strabism, camptodactyly/ hypoplasia of the last falanx III-V fingers, arachnodactyly, “hitch hiker” thumb, severe mental retardation; -Hyperthelorism, ptosis, long philtrum, biphid ugula, brachi-metatarsy IV left finger, mild mental retardation. Cytogenetic/molecular studies: 46,XY del(9)(p24.3), 46,XY pter del(9)(p23) (TelVysion9p-); SRY and DYZ3 were positive for both patients. Endocrinological evaluation (at 1.9 and 7.2 yrs. of age, respectively): GnRH test (FSH basal 2.0/44.3, peak 7.0/130.2 mcU/ml; LH basal 0.4/2.5, peak 14,6/37.3 mcU/ml); Testosterone (basal 0.2/0.3, post hCG -/0.2 ng/ml). Considerations: Some of the clinical characteristics of the patients are frequently observed in subtelomeric rearrangements, independently from the specific region involved. Genital abnormalities, on the contrary, depend on the chromosome involved, although out of 100 cases of the 9p- syndrome thus far reported, only 23 showed sex reversal. The reasons for this phenotypic variability in the presence of subtelomeric deletions is not obvious. Further studies are necessary to understand better the gene(s) organisation in autosomal impairment of sex differentiation.