Incidence, Prevalence, Diagnostic Delay, and Clinical Presentation of Female 46,XY Disorders of Sex Development.
The prevalence of phenotypic females with a 46,XY karyotype is low, thus current knowledge about age and clinical presentation at diagnosis is sparse even for the most frequent conditions, androgen insensitivity syndrome (AIS), and gonadal dysgenesis.



To estimate incidence, prevalence, age at diagnosis, and clinical presentation at diagnosis in 46,XY females.



A nationwide study covering all known females with a 46,XY karyotype in Denmark since 1960. The diagnosis of 46,XY disorder of sex development (DSD) was determined by medical record evaluation, data from the Danish National Patient Registry, and genetic testing, if available.



A total of 166 females registered as 46,XY females in the Danish Cytogenetic Central Registry were identified.



A total of 124 females were classified as having 46,XY DSD, 78 with AIS and 25 with gonadal dysgenesis, whereas the remaining subjects had a variety of different diagnoses. The prevalence of 46,XY females was 6.4 per 100 000 live born females, and for AIS and gonadal dysgenesis, it was 4.1 and 1.5 per 100 000, respectively. Median age at diagnosis was 7.5 years (95% confidence interval, 4.0-13.5; range, 0-34 y) in AIS and 17.0 years (95% confidence interval, 15.5-19.0; range, 0-28 y) in gonadal dysgenesis (P = .001). Clinical presentation was dependent on cause of DSD.



The first estimate on prevalence of 46,XY females is 6.4 per 100 000 live born females. The presentation of AIS and gonadal dysgenesis is distinctly different, with AIS being diagnosed during childhood and gonadal dysgenesis during pubertal years. The presenting phenotype is dependent on the cause of 46,XY DSD.
Department of Endocrinology and Internal Medicine (A.B., K.S., M.H.V., C.H.G.), Aarhus University Hospital, 8000 Aarhus C, Denmark; Department of Growth and Reproduction (T.H.J., K.M.M.), Rigshospitalet, University of Copenhagen, and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC) (T.H.J., K.M.M.), Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark; Center of Rare Diseases (K.S.), Department of Pediatrics, and Department of Molecular Medicine (C.H.G.), Aarhus University Hospital, 8200 Aarhus N, Denmark; and Fertility Clinic (J.F.), Odense University Hospital, 5000 Odense C, Denmark.
Agnethe
A
Berglund
Department of Endocrinology and Internal Medicine (A.B., K.S., M.H.V., C.H.G.), Aarhus University Hospital, 8000 Aarhus C, Denmark; Department of Growth and Reproduction (T.H.J., K.M.M.), Rigshospitalet, University of Copenhagen, and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC) (T.H.J., K.M.M.), Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark; Center of Rare Diseases (K.S.), Department of Pediatrics, and Department of Molecular Medicine (C.H.G.), Aarhus University Hospital, 8200 Aarhus N, Denmark; and Fertility Clinic (J.F.), Odense University Hospital, 5000 Odense C, Denmark.
Trine H
TH
Johannsen
Department of Endocrinology and Internal Medicine (A.B., K.S., M.H.V., C.H.G.), Aarhus University Hospital, 8000 Aarhus C, Denmark; Department of Growth and Reproduction (T.H.J., K.M.M.), Rigshospitalet, University of Copenhagen, and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC) (T.H.J., K.M.M.), Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark; Center of Rare Diseases (K.S.), Department of Pediatrics, and Department of Molecular Medicine (C.H.G.), Aarhus University Hospital, 8200 Aarhus N, Denmark; and Fertility Clinic (J.F.), Odense University Hospital, 5000 Odense C, Denmark.
Kirstine
K
Stochholm
Department of Endocrinology and Internal Medicine (A.B., K.S., M.H.V., C.H.G.), Aarhus University Hospital, 8000 Aarhus C, Denmark; Department of Growth and Reproduction (T.H.J., K.M.M.), Rigshospitalet, University of Copenhagen, and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC) (T.H.J., K.M.M.), Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark; Center of Rare Diseases (K.S.), Department of Pediatrics, and Department of Molecular Medicine (C.H.G.), Aarhus University Hospital, 8200 Aarhus N, Denmark; and Fertility Clinic (J.F.), Odense University Hospital, 5000 Odense C, Denmark.
Mette H
MH
Viuff
Department of Endocrinology and Internal Medicine (A.B., K.S., M.H.V., C.H.G.), Aarhus University Hospital, 8000 Aarhus C, Denmark; Department of Growth and Reproduction (T.H.J., K.M.M.), Rigshospitalet, University of Copenhagen, and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC) (T.H.J., K.M.M.), Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark; Center of Rare Diseases (K.S.), Department of Pediatrics, and Department of Molecular Medicine (C.H.G.), Aarhus University Hospital, 8200 Aarhus N, Denmark; and Fertility Clinic (J.F.), Odense University Hospital, 5000 Odense C, Denmark.
Jens
J
Fedder
Department of Endocrinology and Internal Medicine (A.B., K.S., M.H.V., C.H.G.), Aarhus University Hospital, 8000 Aarhus C, Denmark; Department of Growth and Reproduction (T.H.J., K.M.M.), Rigshospitalet, University of Copenhagen, and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC) (T.H.J., K.M.M.), Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark; Center of Rare Diseases (K.S.), Department of Pediatrics, and Department of Molecular Medicine (C.H.G.), Aarhus University Hospital, 8200 Aarhus N, Denmark; and Fertility Clinic (J.F.), Odense University Hospital, 5000 Odense C, Denmark.
Katharina M
KM
Main
Department of Endocrinology and Internal Medicine (A.B., K.S., M.H.V., C.H.G.), Aarhus University Hospital, 8000 Aarhus C, Denmark; Department of Growth and Reproduction (T.H.J., K.M.M.), Rigshospitalet, University of Copenhagen, and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC) (T.H.J., K.M.M.), Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark; Center of Rare Diseases (K.S.), Department of Pediatrics, and Department of Molecular Medicine (C.H.G.), Aarhus University Hospital, 8200 Aarhus N, Denmark; and Fertility Clinic (J.F.), Odense University Hospital, 5000 Odense C, Denmark.
Claus H
CH
Gravholt
D000293:Adolescent; D000328:Adult; D013734:Androgen-Insensitivity Syndrome / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D057210:Delayed Diagnosis; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006061:Gonadal Dysgenesis, 46,XY / Q000175:diagnosis / Q000453:epidemiology* / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012042:Registries / Q000706:statistics & numerical data*; D055815:Young Adult