title: Disorders of sex development: a genetic study of patients in a multidisciplinary clinic.
abstract: Sex development is a process under genetic control directing both the bi-potential gonads to become either a testis or an ovary, and the consequent differentiation of internal ducts and external genitalia. This complex series of events can be altered by a large number of genetic and non-genetic factors. Disorders of sex development (DSD) are all the medical conditions characterized by an atypical chromosomal, gonadal, or phenotypical sex. Incomplete knowledge of the genetic mechanisms involved in sex development results in a low probability of determining the molecular definition of the genetic defect in many of the patients. In this study, we describe the clinical, cytogenetic, and molecular study of 88 cases with DSD, including 29 patients with 46,XY and disorders in androgen synthesis or action, 18 with 46,XX and disorders in androgen excess, 17 with 46,XY and disorders of gonadal (testicular) development, 11 classified as 46,XX other, eight with 46,XX and disorders of gonadal (ovarian) development, and five with sex chromosome anomalies. In total, we found a genetic variant in 56 out of 88 of them, leading to the clinical classification of every patient, and we outline the different steps required for a coherent genetic testing approach. In conclusion, our results highlight the fact that each category of DSD is related to a large number of different DNA alterations, thus requiring multiple genetic studies to achieve a precise etiological diagnosis for each patient.
authors.affiliation: Department of Molecular MedicineMedical Genetics, San Camillo-Forlanini Hospital, Sapienza University, A.O. San Camillo-Forlanini, Padiglione Morgagni, I piano, UOC Laboratorio di Genetica Medica, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatrics and HematologySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, ItalyPsychology DepartmentSan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Dipartimento di Pscicologia, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatric SurgerySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Laino
authors.affiliation: Department of Molecular MedicineMedical Genetics, San Camillo-Forlanini Hospital, Sapienza University, A.O. San Camillo-Forlanini, Padiglione Morgagni, I piano, UOC Laboratorio di Genetica Medica, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatrics and HematologySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, ItalyPsychology DepartmentSan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Dipartimento di Pscicologia, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatric SurgerySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Majore
authors.affiliation: Department of Molecular MedicineMedical Genetics, San Camillo-Forlanini Hospital, Sapienza University, A.O. San Camillo-Forlanini, Padiglione Morgagni, I piano, UOC Laboratorio di Genetica Medica, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatrics and HematologySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, ItalyPsychology DepartmentSan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Dipartimento di Pscicologia, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatric SurgerySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Preziosi
authors.affiliation: Department of Molecular MedicineMedical Genetics, San Camillo-Forlanini Hospital, Sapienza University, A.O. San Camillo-Forlanini, Padiglione Morgagni, I piano, UOC Laboratorio di Genetica Medica, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatrics and HematologySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, ItalyPsychology DepartmentSan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Dipartimento di Pscicologia, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatric SurgerySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Grammatico
authors.affiliation: Department of Molecular MedicineMedical Genetics, San Camillo-Forlanini Hospital, Sapienza University, A.O. San Camillo-Forlanini, Padiglione Morgagni, I piano, UOC Laboratorio di Genetica Medica, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatrics and HematologySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, ItalyPsychology DepartmentSan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Dipartimento di Pscicologia, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatric SurgerySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, Italy.
authors.forename: Carmelilia
authors.initials: C
authors.lastname: De Bernardo
authors.affiliation: Department of Molecular MedicineMedical Genetics, San Camillo-Forlanini Hospital, Sapienza University, A.O. San Camillo-Forlanini, Padiglione Morgagni, I piano, UOC Laboratorio di Genetica Medica, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatrics and HematologySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, ItalyPsychology DepartmentSan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Dipartimento di Pscicologia, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatric SurgerySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Scommegna
authors.affiliation: Department of Molecular MedicineMedical Genetics, San Camillo-Forlanini Hospital, Sapienza University, A.O. San Camillo-Forlanini, Padiglione Morgagni, I piano, UOC Laboratorio di Genetica Medica, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatrics and HematologySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, ItalyPsychology DepartmentSan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Dipartimento di Pscicologia, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatric SurgerySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Rapone
authors.affiliation: Department of Molecular MedicineMedical Genetics, San Camillo-Forlanini Hospital, Sapienza University, A.O. San Camillo-Forlanini, Padiglione Morgagni, I piano, UOC Laboratorio di Genetica Medica, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatrics and HematologySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, ItalyPsychology DepartmentSan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Dipartimento di Pscicologia, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatric SurgerySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, Italy.
authors.forename: Giacinto
authors.initials: G
authors.lastname: Marrocco
authors.affiliation: Department of Molecular MedicineMedical Genetics, San Camillo-Forlanini Hospital, Sapienza University, A.O. San Camillo-Forlanini, Padiglione Morgagni, I piano, UOC Laboratorio di Genetica Medica, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatrics and HematologySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, ItalyPsychology DepartmentSan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Dipartimento di Pscicologia, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatric SurgerySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, Italy i.bottillo@gmail.com.
authors.forename: Irene
authors.initials: I
authors.lastname: Bottillo
authors.affiliation: Department of Molecular MedicineMedical Genetics, San Camillo-Forlanini Hospital, Sapienza University, A.O. San Camillo-Forlanini, Padiglione Morgagni, I piano, UOC Laboratorio di Genetica Medica, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatrics and HematologySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, ItalyPsychology DepartmentSan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Dipartimento di Pscicologia, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatric SurgerySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Grammatico
keywords: DSD; disorders of ovarian development; disorders of sex development; disorders of testicular development