engleski

TWO SIBLINGS WITH 9p MONOSOMY AND 4p TRISOMY, ASSOCIATED WITH NORMAL PUBERTAL DEVELOPMENT IN 46, XX PATIENT, AND SEX REVERSAL, POSTNATAL VIRILIZATION, TRUE HERMAPHRODITISM AND BILATERAL GONADOBLASTOMA IN 46, XY PATIENT

BACKGROUND The 9p deletion with 4p trisomy is a rare disorder, previously described in only 2 patients (1). Distal 9p monosomy is associated with 46, XY sex reversal due to loss of 9p sex-determining genes DMRT1 and DMRT2. So far, in only one del(9p) patient ovarian tissue was found (bilateral ovotestes) (2). We present 2 siblings with 9p monosomy and 4p trisomy. Their father is the healthy carrier of balanced 4p ; 9p translocation. CASE REPORTS Patient 1. is a 19-year-old female with 46, XX, der(9), t(4 ; 9)(p14p24) karyotype. Her features were consistent with del(9p) and dup(4p) syndromes (short stature, obesity, mental retardation, kyphoscoliosis, hypertonia, prominent forehead, wide nasal bridge, thin upper lip, long philtrum, irregular teeth, abnormal ears, short neck, flexion contractures, 11 pairs of ribs, hypoplastic scapulae). She had female external genitalia, normal pubertal development and regular periods. Patient 2. is a 6-month-old female with 46, XY, der(9), t(4 ; 9)(p14p24) karyotype found on amniocentesis and confirmed postnatally. She had normal female external genitalia and features in common with both the del(9p) and dup(4p) syndromes (flat occiput, midface hypoplasia, hypertelorism, flat nasal bridge, thin lips, short neck, kyphoscoliosis, widely spaced hypoplastic nipples, puffy hands and feet, hypoplastic nails, joint contractures, 11 pairs of ribs, hypoplastic scapulae and iliac wings, congenital heart disease, hypotonia, delayed developmental milestones and sex reversal). Laboratory findings at the age of 1 year revealed elevated gonadotropins and slightly elevated testosterone (FSH 36 IU/L /ref.1-4/, LH 8 IU/L /ref. 0.02-0.2/, T 0.3 nmol/L /ref.0.05-0.2/, E2 50 pmol /ref. 20-70/). Clitoral enlargement (1.8 cm) was noted and bilateral gonadectomy was performed. On histologic examination, the left gonad consisted of testicular tissue, epididymus and spermatic cord and the right gonad was comprised of ovarian tissue and Fallopian tube. Bilateral gonadoblastoma was found. The same chromosomal abnormalities were found in gonadal tissue. CONCLUSION Patient 2. is the first 46, XY, del(9p) female in which postnatal virilization occurred and in which different gonads (ovary and testis) separately developed. The possibility of development of gonadoblastoma in these patients prompt gonadectomy at an early age. The finding of diverse differentiation outcomes in siblings carrying the same 4p ; 9p translocation suggests the complex role of the 9p sex-determining genes.

9p monosomy; 4p trisomy; true hermaphroditism; sex reversal

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