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Sex reversal

MedGen UID:
868596
Concept ID:
C4022995
Finding
HPO: HP:0012245

Definition

Development of the reproductive system is inconsistent with the chromosomal sex. [from HPO]

Conditions with this feature

46,XY disorder of sex development due to testicular 17,20-desmolase deficiency
MedGen UID:
333416
Concept ID:
C1839840
Disease or Syndrome
46,XY sex reversal 2
MedGen UID:
341190
Concept ID:
C1848296
Disease or Syndrome
46,XY sex reversal 7
MedGen UID:
383876
Concept ID:
C1856273
Congenital Abnormality
Camptomelic dysplasia
MedGen UID:
354620
Concept ID:
C1861922
Disease or Syndrome
Campomelic dysplasia (CD) is a skeletal dysplasia characterized by distinctive facies, Pierre Robin sequence with cleft palate, shortening and bowing of long bones, and clubfeet. Other findings include laryngotracheomalacia with respiratory compromise and ambiguous genitalia or normal female external genitalia in most individuals with a 46,XY karyotype. Many affected infants die in the neonatal period; additional findings identified in long-term survivors include short stature, cervical spine instability with cord compression, progressive scoliosis, and hearing impairment.
Endocrine-cerebro-osteodysplasia syndrome
MedGen UID:
390740
Concept ID:
C2675227
Disease or Syndrome
Endocrine-cerebro-osteodysplasia (ECO) syndrome is characterized by various anomalies of the endocrine, cerebral, and skeletal systems resulting in neonatal mortality.
SERKAL syndrome
MedGen UID:
394528
Concept ID:
C2678492
Disease or Syndrome
Syndrome that has characteristics of female to male sex reversal and developmental anomalies of the kidneys, adrenal glands and lungs. The syndrome is lethal and has been described in three fetuses. It is caused by homozygous missense mutations in the WNT4 gene. It is transmitted as an autosomal recessive trait.
46,XX sex reversal 1
MedGen UID:
411324
Concept ID:
C2748895
Disease or Syndrome
Nonsyndromic 46,XX testicular disorders/differences of sex development (DSD) are characterized by: the presence of a 46,XX karyotype; external genitalia ranging from typical male to ambiguous; two testicles; azoospermia; absence of müllerian structures; and absence of other syndromic features, such as congenital anomalies outside of the genitourinary system, learning disorders / cognitive impairment, or behavioral issues. Approximately 85% of individuals with nonsyndromic 46,XX testicular DSD present after puberty with normal pubic hair and normal penile size but small testes, gynecomastia, and sterility resulting from azoospermia. Approximately 15% of individuals with nonsyndromic 46,XX testicular DSD present at birth with ambiguous genitalia. Gender role and gender identity are reported as male. If untreated, males with 46,XX testicular DSD experience the consequences of testosterone deficiency.
46,XY sex reversal 1
MedGen UID:
412662
Concept ID:
C2748896
Disease or Syndrome
Sex reversal in an individual with 46,XY karyotype caused by point mutations or deletions in the SRY gene, encoding sex-determining region Y protein.
46,XX sex reversal 2
MedGen UID:
411414
Concept ID:
C2749215
Disease or Syndrome
Nonsyndromic 46,XX testicular disorders/differences of sex development (DSD) are characterized by: the presence of a 46,XX karyotype; external genitalia ranging from typical male to ambiguous; two testicles; azoospermia; absence of müllerian structures; and absence of other syndromic features, such as congenital anomalies outside of the genitourinary system, learning disorders / cognitive impairment, or behavioral issues. Approximately 85% of individuals with nonsyndromic 46,XX testicular DSD present after puberty with normal pubic hair and normal penile size but small testes, gynecomastia, and sterility resulting from azoospermia. Approximately 15% of individuals with nonsyndromic 46,XX testicular DSD present at birth with ambiguous genitalia. Gender role and gender identity are reported as male. If untreated, males with 46,XX testicular DSD experience the consequences of testosterone deficiency.
46,XY sex reversal 5
MedGen UID:
414349
Concept ID:
C2751317
Disease or Syndrome
46,XY sex reversal 4
MedGen UID:
416704
Concept ID:
C2752149
Congenital Abnormality
Sex reversal in an individual associated with a 9p24.3 deletion.
Congenital adrenal insuffiency with 46, XY sex reversal OR 46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency
MedGen UID:
462405
Concept ID:
C3151055
Disease or Syndrome
P450scc deficiency is a rare disorder that can present as acute adrenal insufficiency in infancy or childhood. ACTH and plasma renin activity are grossly elevated and adrenal steroids are inappropriately low or absent; the 46,XY patients have female external genitalia, sometimes with clitoromegaly. The phenotypic spectrum ranges from prematurity, complete underandrogenization, and severe early-onset adrenal failure to term birth with clitoromegaly and later-onset adrenal failure (summary by Kim et al., 2008). Although hormonal and phenotypic features can resemble those of congenital lipoid adrenal hyperplasia (lipoid CAH; 201710), no patient with P450scc deficiency has been described with the massive adrenal enlargement typical of lipoid CAH (summary by Sahakitrungruang et al., 2011).
46,XY sex reversal 6
MedGen UID:
462414
Concept ID:
C3151064
Disease or Syndrome
46,XX sex reversal 3
MedGen UID:
463132
Concept ID:
C3151782
Disease or Syndrome
Nonsyndromic 46,XX testicular disorders/differences of sex development (DSD) are characterized by: the presence of a 46,XX karyotype; external genitalia ranging from typical male to ambiguous; two testicles; azoospermia; absence of müllerian structures; and absence of other syndromic features, such as congenital anomalies outside of the genitourinary system, learning disorders / cognitive impairment, or behavioral issues. Approximately 85% of individuals with nonsyndromic 46,XX testicular DSD present after puberty with normal pubic hair and normal penile size but small testes, gynecomastia, and sterility resulting from azoospermia. Approximately 15% of individuals with nonsyndromic 46,XX testicular DSD present at birth with ambiguous genitalia. Gender role and gender identity are reported as male. If untreated, males with 46,XX testicular DSD experience the consequences of testosterone deficiency.
46,XY sex reversal 3
MedGen UID:
483746
Concept ID:
C3489793
Congenital Abnormality
46,XY sex reversal 9
MedGen UID:
863566
Concept ID:
C4015129
Disease or Syndrome
46,XY sex reversal 10
MedGen UID:
897538
Concept ID:
C4225331
Disease or Syndrome
46,XY females with gonadal dysgenesis have streak gonads but look like normal females at birth. They do not develop secondary sexual characteristics at puberty and do not menstruate. They are chromatin-negative and are usually of normal stature, without the somatic stigmata of Turner syndrome (see 163950) (summary by Mann et al., 1983). For a discussion of genetic heterogeneity of 46,XY sex reversal, see SRXY1 (400044).

Professional guidelines

PubMed

Kanaan BA, Al-Ouqaili MTS, Murshid RM
PeerJ 2023;11:e15267. Epub 2023 May 26 doi: 10.7717/peerj.15267. PMID: 37255590Free PMC Article
Ramanathan AS, Vijayan M, Rajagopal S, Rajendiran P, Senguttuvan P
Mol Cell Biochem 2017 Feb;426(1-2):177-181. Epub 2016 Nov 25 doi: 10.1007/s11010-016-2889-5. PMID: 27885584
Mittwoch U
Hum Genet 1992 Jul;89(5):467-79. doi: 10.1007/BF00219168. PMID: 1634224

Recent clinical studies

Etiology

Hart D, Rodríguez Gutiérrez D, Biason-Lauber A
Sex Dev 2022;16(2-3):162-170. Epub 2022 Mar 9 doi: 10.1159/000522164. PMID: 35263754
Ridnik M, Schoenfelder S, Gonen N
Sex Dev 2021;15(5-6):317-334. Epub 2021 Oct 28 doi: 10.1159/000519244. PMID: 34710870Free PMC Article
Ruiz-García A, Roco ÁS, Bullejos M
Sex Dev 2021;15(1-3):157-167. Epub 2021 May 17 doi: 10.1159/000515220. PMID: 34000727
Hughes IA, Deeb A
Best Pract Res Clin Endocrinol Metab 2006 Dec;20(4):577-98. doi: 10.1016/j.beem.2006.11.003. PMID: 17161333
Zenteno-Ruiz JC, Kofman-Alfaro S, Méndez JP
Arch Med Res 2001 Nov-Dec;32(6):559-66. doi: 10.1016/s0188-4409(01)00322-8. PMID: 11750731

Diagnosis

Hill P, While GM, Burridge CP, Ezaz T, Munch KL, McVarish M, Wapstra E
Proc Biol Sci 2022 Jun 8;289(1976):20220689. Epub 2022 Jun 1 doi: 10.1098/rspb.2022.0689. PMID: 35642367Free PMC Article
Ridnik M, Schoenfelder S, Gonen N
Sex Dev 2021;15(5-6):317-334. Epub 2021 Oct 28 doi: 10.1159/000519244. PMID: 34710870Free PMC Article
Jain V, Sen B
J Pediatr Orthop B 2014 Sep;23(5):485-8. doi: 10.1097/BPB.0000000000000058. PMID: 24800790
Hughes IA, Deeb A
Best Pract Res Clin Endocrinol Metab 2006 Dec;20(4):577-98. doi: 10.1016/j.beem.2006.11.003. PMID: 17161333
Baumstark A, Barbi G, Djalali M, Geerkens C, Mitulla B, Mattfeldt T, de Almeida JC, Vargas FR, Llerena Júnior JC, Vogel W, Just W
Hum Genet 1996 Jan;97(1):79-86. doi: 10.1007/BF00218838. PMID: 8557267

Therapy

Stewart MK, Mattiske DM, Pask AJ
Int J Mol Sci 2020 Nov 8;21(21) doi: 10.3390/ijms21218377. PMID: 33171657Free PMC Article
Bélanger C, Bérubé-Simard FA, Leduc E, Bernas G, Campeau PM, Lalani SR, Martin DM, Bielas S, Moccia A, Srivastava A, Silversides DW, Pilon N
Proc Natl Acad Sci U S A 2018 Jan 23;115(4):E620-E629. Epub 2018 Jan 8 doi: 10.1073/pnas.1715378115. PMID: 29311329Free PMC Article
Juul A, Almstrup K, Andersson AM, Jensen TK, Jørgensen N, Main KM, Rajpert-De Meyts E, Toppari J, Skakkebæk NE
Nat Rev Endocrinol 2014 Sep;10(9):553-62. Epub 2014 Jun 17 doi: 10.1038/nrendo.2014.97. PMID: 24935122
Ravel C, Hyon C, Siffroi JP, Christin-Maitre S
Ann Endocrinol (Paris) 2014 May;75(2):126-7. Epub 2014 Apr 21 doi: 10.1016/j.ando.2014.03.003. PMID: 24751136
Chen L, Ding XP, Wei X, Li LX
Genet Mol Res 2014 Mar 12;13(1):1518-26. doi: 10.4238/2014.March.12.4. PMID: 24668626

Prognosis

Cai P, Zhang W, Jiang S, Xiong Y, Yuan H, Gao Z, Gao X, Ma C, Zhou Y, Gong Y, Qiao H, Jin S, Fu H
Int J Mol Sci 2023 Sep 19;24(18) doi: 10.3390/ijms241814306. PMID: 37762609Free PMC Article
Nemesházi E, Bókony V
Bioessays 2022 Jul;44(7):e2200039. Epub 2022 May 11 doi: 10.1002/bies.202200039. PMID: 35543235
Jones MEH, Pistevos JCA, Cooper N, Lappin AK, Georges A, Hutchinson MN, Holleley CE
J Exp Zool A Ecol Integr Physiol 2020 Apr;333(4):252-263. Epub 2020 Feb 14 doi: 10.1002/jez.2353. PMID: 32061035
Jain V, Sen B
J Pediatr Orthop B 2014 Sep;23(5):485-8. doi: 10.1097/BPB.0000000000000058. PMID: 24800790
Barthold JS
J Urol 2011 Feb;185(2):393-400. Epub 2010 Dec 17 doi: 10.1016/j.juro.2010.09.083. PMID: 21167531

Clinical prediction guides

Hill P, While GM, Burridge CP, Ezaz T, Munch KL, McVarish M, Wapstra E
Proc Biol Sci 2022 Jun 8;289(1976):20220689. Epub 2022 Jun 1 doi: 10.1098/rspb.2022.0689. PMID: 35642367Free PMC Article
Nemesházi E, Bókony V
Bioessays 2022 Jul;44(7):e2200039. Epub 2022 May 11 doi: 10.1002/bies.202200039. PMID: 35543235
Li Y, Chen Z, Liu H, Li Q, Lin X, Ji S, Li R, Li S, Fan W, Zhao H, Zhu Z, Hu W, Zhou Y, Luo D
Genomics Proteomics Bioinformatics 2021 Dec;19(6):873-881. Epub 2021 Nov 25 doi: 10.1016/j.gpb.2021.10.001. PMID: 34839012Free PMC Article
Zenteno-Ruiz JC, Kofman-Alfaro S, Méndez JP
Arch Med Res 2001 Nov-Dec;32(6):559-66. doi: 10.1016/s0188-4409(01)00322-8. PMID: 11750731
Mittwoch U
Hum Genet 1992 Jul;89(5):467-79. doi: 10.1007/BF00219168. PMID: 1634224

Recent systematic reviews

Yu Y, Chen M, Shen ZG
Ecotoxicol Environ Saf 2023 Nov 15;267:115654. Epub 2023 Nov 1 doi: 10.1016/j.ecoenv.2023.115654. PMID: 37918334

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