DISORDERS OR DIFFERENCES IN SEX DIFFERENTIATION

DISORDERS OR DIFFERENCES IN SEX DIFFERENTIATION

Some, but not all, children with abnormalities of their sex chromosomes, gonads or reproductive anatomy are consid ered to have a disorder or di ff erence in sex di ff erentiation (DSD). Isolated undescended testes, hypospadias and labial adhesions are excluded. Unfortunately , there is no consensus on the indications, timing, best procedures or how to evaluate DSD surgery . The classification of disorders into groups is complex and controversial. For simplicity , only the following groups are described here: 46-XX DSD, 46-XY DSD and sex- chromosome mosaicism DSD variants. DSD management benefits when the paediatric urologist works in a multi disciplinary team, including a geneticist, endocrinologist, an adolescent gynaecologist and a psychologist. The 46-XX DSD group is exemplified by congenital adrenal hyperplasia (CAH), in which gender is usually straight forward (female), except with late diagnoses and severe mas culinisation. At birth, the urethra may open on a prominent genital tubercle, appearing like a small phallus and looking sim ilar to a 46-XY boy with severe hypospadias and non-palpab testes. In 46-XX CAH, the vagina opens into the posterior wall of the urethra a variable distance from the bladder neck but not higher than where the verumontanum, a Müllerian structure, is typically located in the male urethra. Genital f fusion varies from a vulval-like to a scrotal-like appearance. The 46-XY DSD group is exemplified by androgen insensitivity syndrome (AIS), 17 β hydroxysteroid dehydroge nase (17 β HSD) deficiency and 5 α reductase deficiency . AIS is complete (CAIS), with a feminine phenotype, or partial (PAIS), in which the external genitals are undermasculinised at birth and undervirilised at puberty . Infants with CAIS (reared as gir ls) may present with bilateral inguinal hernias or with ingui nal testes thought to be prolapsed ovaries. Similarly , those with 17 β HSD deficiency and 5 α reductase deficiency , having low androgens, may have an exter nal feminine phenotype with palpable inguinal testes undergoing virilisation at puberty . In challenging cases, controversy surrounds gender assignment, sex of rearing and surgery . Johannes Peter Müller , 1801–1858, German physiologist and comparative anatomist after whom the paramesonephric duct structures are named. P aul Mitrofano ff , b. 1934, paediatric surgeon, Rouen, France, devised the appendicovesicostomy in the mid-1970s. be left alone until the individual can determine their gender for themselves? Or, if female sex rearing is decided on, should they be removed ear ly to avoid virilisation at puberty? If conserva - tive management is chosen, temporarily blocking virilisation with a gonadotropin-releasing hormone analogue is an option until gender identity is determined. Sex-chromosome mosaicism is exemplified by 45X/46XY DSD. These individuals may have a hemi - - scrotum containing a testis-like gonad, paired with a labia majora with an inguinal or impalpable streak gonad; a streak gonad has stromal tissue without tubules or follicles. There is usually severe hypospadias. DISORDERS OR DIFFERENCES IN SEX DIFFERENTIATION

Some, but not all, children with abnormalities of their sex chromosomes, gonads or reproductive anatomy are consid ered to have a disorder or di ff erence in sex di ff erentiation (DSD). Isolated undescended testes, hypospadias and labial adhesions are excluded. Unfortunately , there is no consensus on the indications, timing, best procedures or how to evaluate DSD surgery . The classification of disorders into groups is complex and controversial. For simplicity , only the following groups are described here: 46-XX DSD, 46-XY DSD and sex- chromosome mosaicism DSD variants. DSD management benefits when the paediatric urologist works in a multi disciplinary team, including a geneticist, endocrinologist, an adolescent gynaecologist and a psychologist. The 46-XX DSD group is exemplified by congenital adrenal hyperplasia (CAH), in which gender is usually straight forward (female), except with late diagnoses and severe mas culinisation. At birth, the urethra may open on a prominent genital tubercle, appearing like a small phallus and looking sim ilar to a 46-XY boy with severe hypospadias and non-palpab testes. In 46-XX CAH, the vagina opens into the posterior wall of the urethra a variable distance from the bladder neck but not higher than where the verumontanum, a Müllerian structure, is typically located in the male urethra. Genital f fusion varies from a vulval-like to a scrotal-like appearance. The 46-XY DSD group is exemplified by androgen insensitivity syndrome (AIS), 17 β hydroxysteroid dehydroge nase (17 β HSD) deficiency and 5 α reductase deficiency . AIS is complete (CAIS), with a feminine phenotype, or partial (PAIS), in which the external genitals are undermasculinised at birth and undervirilised at puberty . Infants with CAIS (reared as gir ls) may present with bilateral inguinal hernias or with ingui nal testes thought to be prolapsed ovaries. Similarly , those with 17 β HSD deficiency and 5 α reductase deficiency , having low androgens, may have an exter nal feminine phenotype with palpable inguinal testes undergoing virilisation at puberty . In challenging cases, controversy surrounds gender assignment, sex of rearing and surgery . Johannes Peter Müller , 1801–1858, German physiologist and comparative anatomist after whom the paramesonephric duct structures are named. P aul Mitrofano ff , b. 1934, paediatric surgeon, Rouen, France, devised the appendicovesicostomy in the mid-1970s. be left alone until the individual can determine their gender for themselves? Or, if female sex rearing is decided on, should they be removed ear ly to avoid virilisation at puberty? If conserva - tive management is chosen, temporarily blocking virilisation with a gonadotropin-releasing hormone analogue is an option until gender identity is determined. Sex-chromosome mosaicism is exemplified by 45X/46XY DSD. These individuals may have a hemi - - scrotum containing a testis-like gonad, paired with a labia majora with an inguinal or impalpable streak gonad; a streak gonad has stromal tissue without tubules or follicles. There is usually severe hypospadias. DISORDERS OR DIFFERENCES IN SEX DIFFERENTIATION

Some, but not all, children with abnormalities of their sex chromosomes, gonads or reproductive anatomy are consid ered to have a disorder or di ff erence in sex di ff erentiation (DSD). Isolated undescended testes, hypospadias and labial adhesions are excluded. Unfortunately , there is no consensus on the indications, timing, best procedures or how to evaluate DSD surgery . The classification of disorders into groups is complex and controversial. For simplicity , only the following groups are described here: 46-XX DSD, 46-XY DSD and sex- chromosome mosaicism DSD variants. DSD management benefits when the paediatric urologist works in a multi disciplinary team, including a geneticist, endocrinologist, an adolescent gynaecologist and a psychologist. The 46-XX DSD group is exemplified by congenital adrenal hyperplasia (CAH), in which gender is usually straight forward (female), except with late diagnoses and severe mas culinisation. At birth, the urethra may open on a prominent genital tubercle, appearing like a small phallus and looking sim ilar to a 46-XY boy with severe hypospadias and non-palpab testes. In 46-XX CAH, the vagina opens into the posterior wall of the urethra a variable distance from the bladder neck but not higher than where the verumontanum, a Müllerian structure, is typically located in the male urethra. Genital f fusion varies from a vulval-like to a scrotal-like appearance. The 46-XY DSD group is exemplified by androgen insensitivity syndrome (AIS), 17 β hydroxysteroid dehydroge nase (17 β HSD) deficiency and 5 α reductase deficiency . AIS is complete (CAIS), with a feminine phenotype, or partial (PAIS), in which the external genitals are undermasculinised at birth and undervirilised at puberty . Infants with CAIS (reared as gir ls) may present with bilateral inguinal hernias or with ingui nal testes thought to be prolapsed ovaries. Similarly , those with 17 β HSD deficiency and 5 α reductase deficiency , having low androgens, may have an exter nal feminine phenotype with palpable inguinal testes undergoing virilisation at puberty . In challenging cases, controversy surrounds gender assignment, sex of rearing and surgery . Johannes Peter Müller , 1801–1858, German physiologist and comparative anatomist after whom the paramesonephric duct structures are named. P aul Mitrofano ff , b. 1934, paediatric surgeon, Rouen, France, devised the appendicovesicostomy in the mid-1970s. be left alone until the individual can determine their gender for themselves? Or, if female sex rearing is decided on, should they be removed ear ly to avoid virilisation at puberty? If conserva - tive management is chosen, temporarily blocking virilisation with a gonadotropin-releasing hormone analogue is an option until gender identity is determined. Sex-chromosome mosaicism is exemplified by 45X/46XY DSD. These individuals may have a hemi - - scrotum containing a testis-like gonad, paired with a labia majora with an inguinal or impalpable streak gonad; a streak gonad has stromal tissue without tubules or follicles. There is usually severe hypospadias.