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Hypospadias 2, X-linked(HYSP2)

MedGen UID:
437064
•Concept ID:
C2677879
•
Disease or Syndrome
Synonym: HYSP2
 
Gene (location): MAMLD1 (Xq28)
 
Monarch Initiative: MONDO:0010423
OMIM®: 300758

Clinical features

From HPO
Penoscrotal hypospadias
MedGen UID:
105291
•Concept ID:
C0452147
•
Congenital Abnormality
A severe form of hypospadias in which the urethral opening is located at the junction of the penis and scrotum.
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Professional guidelines

Recent clinical studies

Etiology

The E3 ubiquitin ligase MID1/TRIM18 promotes atypical ubiquitination of the BRCA2-associated factor 35, BRAF35.
Zanchetta ME, Napolitano LMR, Maddalo D, Meroni G
Biochim Biophys Acta Mol Cell Res 2017 Oct;1864(10):1844-1854. Epub 2017 Jul 29 doi: 10.1016/j.bbamcr.2017.07.014. PMID: 28760657
Genitourinary anomalies of pediatric FG syndrome.
Smith JF, Wayment RO, Cartwright PC, Snow BW, Opitz JM
J Urol 2007 Aug;178(2):656-9. Epub 2007 Jun 15 doi: 10.1016/j.juro.2007.04.007. PMID: 17574621
MID1 mutation screening in a large cohort of Opitz G/BBB syndrome patients: twenty-nine novel mutations identified.
Ferrentino R, Bassi MT, Chitayat D, Tabolacci E, Meroni G
Hum Mutat 2007 Feb;28(2):206-7. doi: 10.1002/humu.9480. PMID: 17221865
Isolation and characterisation of the chick orthologue of the Opitz syndrome gene, Mid1, supports a conserved role in vertebrate development.
Richman JM, Fu KK, Cox LL, Sibbons JP, Cox TC
Int J Dev Biol 2002;46(4):441-8. PMID: 12141430
Molecular basis of androgen insensitivity.
Brinkmann A, Jenster G, Ris-Stalpers C, van der Korput H, Brüggenwirth H, Boehmer A, Trapman J
Steroids 1996 Apr;61(4):172-5. doi: 10.1016/0039-128x(96)00008-6. PMID: 8732995

Diagnosis

Opitz GBBB syndrome with total anomalous pulmonary venous connection: A new MID1 gene variant.
Perea-Cabrera M, Granados-Riveron JT, Segura-Stanford B, Moreno-Vargas LM, Prada-Gracia D, Moran-Espinosa MC, Erdmenger J, Diaz-Garcia H, Sánchez-Urbina R
Mol Genet Genomic Med 2023 Sep;11(9):e2234. Epub 2023 Jul 27 doi: 10.1002/mgg3.2234. PMID: 37498300Free PMC Article
Molecular genetics and general management of androgen insensitivity syndrome.
Chen Z, Li P, Lyu Y, Wang Y, Gao K, Wang J, Lan F, Chen F
Intractable Rare Dis Res 2023 May;12(2):71-77. doi: 10.5582/irdr.2023.01024. PMID: 37287652Free PMC Article
Prenatal diagnosis of Simpson-Golabi-Behmel syndrome type 1 with an 814 kb Xq26.2 deletion with the initial presentation of a thick nuchal fold.
Peng HH, Yu CJ, Chen YC, Hsu CC, Chang SD, Chueh HY, Chang YL, Cheng PJ, Lee YC
Taiwan J Obstet Gynecol 2023 Jan;62(1):163-166. doi: 10.1016/j.tjog.2022.06.019. PMID: 36720533
Opitz syndrome: improving clinical interpretation of intronic variants in MID1 gene.
Micale L, Russo F, Mascaro M, Morlino S, Nardella G, Fusco C, Bisceglia L, Meroni G, Castori M
Pediatr Res 2023 Apr;93(5):1208-1215. Epub 2022 Aug 11 doi: 10.1038/s41390-022-02237-y. PMID: 35953512
Oral Methylene Blue Treatment in A Dog with Cytochrome B(5) Reductase Deficiency And 78, XX Testicular Disorder of Sex Development.
Jaffey JA, Struthers JD, Yuh EL, Hostnik ET, Runyan RA, Reading NS
Top Companion Anim Med 2022 Jul-Aug;49:100649. Epub 2022 Feb 22 doi: 10.1016/j.tcam.2022.100649. PMID: 35202847

Therapy

Oral Methylene Blue Treatment in A Dog with Cytochrome B(5) Reductase Deficiency And 78, XX Testicular Disorder of Sex Development.
Jaffey JA, Struthers JD, Yuh EL, Hostnik ET, Runyan RA, Reading NS
Top Companion Anim Med 2022 Jul-Aug;49:100649. Epub 2022 Feb 22 doi: 10.1016/j.tcam.2022.100649. PMID: 35202847
Androgen resistance associated with a qualitative abnormality of the androgen receptor and responsive to high dose androgen therapy.
Grino PB, Isidro-Gutierrez RF, Griffin JE, Wilson JD
J Clin Endocrinol Metab 1989 Mar;68(3):578-84. doi: 10.1210/jcem-68-3-578. PMID: 2918059

Prognosis

A Novel MID1 Mutation Identified in a Patient With Craniofacial Anomalies and X-Linked Intellectual Disability.
Wu Q, Feng X, Yan Y, Yu B, Dai C, Wei J
J Craniofac Surg 2026 Mar 16 doi: 10.1097/SCS.0000000000012575. PMID: 41842826
OTUD5-related rare X-linked multiple congenital anomalies and neurodevelopmental syndrome: clinical findings and review of the literature.
Eroğlu A, Akdağ DG, Ünsel-Bolat G, Tezcan A, Bolat H
Neurogenetics 2026 Mar 16;27(1) doi: 10.1007/s10048-026-00896-1. PMID: 41838201
Opitz syndrome: improving clinical interpretation of intronic variants in MID1 gene.
Micale L, Russo F, Mascaro M, Morlino S, Nardella G, Fusco C, Bisceglia L, Meroni G, Castori M
Pediatr Res 2023 Apr;93(5):1208-1215. Epub 2022 Aug 11 doi: 10.1038/s41390-022-02237-y. PMID: 35953512
OTUD5 Variants Associated With X-Linked Intellectual Disability and Congenital Malformation.
Saida K, Fukuda T, Scott DA, Sengoku T, Ogata K, Nicosia A, Hernandez-Garcia A, Lalani SR, Azamian MS, Streff H, Liu P, Dai H, Mizuguchi T, Miyatake S, Asahina M, Ogata T, Miyake N, Matsumoto N
Front Cell Dev Biol 2021;9:631428. Epub 2021 Mar 3 doi: 10.3389/fcell.2021.631428. PMID: 33748114Free PMC Article
Prenatal diagnosis of maternally inherited X-linked Opitz G/BBB syndrome by chromosomal microarray in a fetus with complex congenital heart disease.
Cheng YK, Huang J, Law KM, Chan YM, Leung TY, Choy KW
Clin Chim Acta 2014 Sep 25;436:140-2. Epub 2014 May 23 doi: 10.1016/j.cca.2014.05.006. PMID: 24863803

Clinical prediction guides

A Novel MID1 Mutation Identified in a Patient With Craniofacial Anomalies and X-Linked Intellectual Disability.
Wu Q, Feng X, Yan Y, Yu B, Dai C, Wei J
J Craniofac Surg 2026 Mar 16 doi: 10.1097/SCS.0000000000012575. PMID: 41842826
OTUD5-related rare X-linked multiple congenital anomalies and neurodevelopmental syndrome: clinical findings and review of the literature.
Eroğlu A, Akdağ DG, Ünsel-Bolat G, Tezcan A, Bolat H
Neurogenetics 2026 Mar 16;27(1) doi: 10.1007/s10048-026-00896-1. PMID: 41838201
Opitz GBBB syndrome with total anomalous pulmonary venous connection: A new MID1 gene variant.
Perea-Cabrera M, Granados-Riveron JT, Segura-Stanford B, Moreno-Vargas LM, Prada-Gracia D, Moran-Espinosa MC, Erdmenger J, Diaz-Garcia H, Sánchez-Urbina R
Mol Genet Genomic Med 2023 Sep;11(9):e2234. Epub 2023 Jul 27 doi: 10.1002/mgg3.2234. PMID: 37498300Free PMC Article
Opitz syndrome: improving clinical interpretation of intronic variants in MID1 gene.
Micale L, Russo F, Mascaro M, Morlino S, Nardella G, Fusco C, Bisceglia L, Meroni G, Castori M
Pediatr Res 2023 Apr;93(5):1208-1215. Epub 2022 Aug 11 doi: 10.1038/s41390-022-02237-y. PMID: 35953512
Dataset of differentially expressed genes in mouse P12 testes in response to the loss of ATRX in Sertoli cells.
Bagheri-Fam S, Alankarage D, Frost ER, Harley VR
Data Brief 2022 Jun;42:108230. Epub 2022 May 2 doi: 10.1016/j.dib.2022.108230. PMID: 35592768Free PMC Article

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      Related medical variations
    • Gene
      Related information in NCBI Gene
    • GTR
      Related information in GTR
    • GTR(Clinical)
      Clinical tests in GTR
    • MeSH
      Related Medical Subject Headings
    • OMIM
      Related records in OMIM
    • OMIM(Genes)
      OMIM records containing genes associated with phenotypes registered in MedGen
    • PMC Articles
      Related information in PubMed Central Links
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