| Domain | Best-supported finding | Quantitative detail | Evidence type/source/date | Ontology-ready annotation |
|---|---|---|---|---|
| Definition / identifiers | PMDS is a congenital disorder of sex development in otherwise normally virilized 46,XY males, characterized by persistence of Müllerian derivatives such as the uterus, fallopian tubes, and upper vagina. | MONDO:0009857; Orphanet:2856 | Aggregated disease-target resource and 2024 human review/case report (pqac-00000000, pqac-00000002) | MONDO:0009857; 46,XY DSD; persistent Müllerian derivatives |
| Causal genes | Biallelic loss-of-function variants in **AMH** cause deficient hormone activity (type 1); biallelic **AMHR2** variants cause receptor resistance (type 2). | Approximately 88% of cases have homozygous or compound-heterozygous variants in these genes; one 157-case review found AMH variants in 40.4%, AMHR2 variants in 45.7%, and neither in 13.9%. | Human cohort/reviews, 2017–2024 (pqac-00000000, pqac-00000001, pqac-00000002) | Genes: AMH, AMHR2; mechanism: germline loss of function; inheritance: autosomal recessive |
| Pathogenic variants | Variant classes include missense, nonsense, frameshift, splice, insertion/deletion, and AMHR2 microdeletions. A recurrent 27-bp AMHR2 kinase-domain deletion is enriched in patients of Northern European origin. | Recurrent deletion reported in 30 patients; 2024 AMHR2 c.1046T>C (p.Ile349Thr) had gnomAD frequency 0.00001591 and no homozygotes. | Human molecular cohorts/reviews and 2024 case report (pqac-00000005, pqac-00000008, pqac-00000016) | Sequence variants in AMH/AMHR2; germline; pathogenic/likely pathogenic/VUS classification per ACMG/AMP |
| Core phenotypes | Principal presentations are bilateral cryptorchidism, unilateral cryptorchidism with contralateral hernia containing Müllerian structures, and transverse testicular ectopia; external virilization is usually normal. | Bilateral intra-abdominal testes approximately 60–70%; hernia uteri inguinalis approximately 20–30%; transverse testicular ectopia approximately 10% in one review. A 2024 review grouped approximately 80% as the bilateral intra-abdominal “female form” and 20% as male forms. | Human case-series/reviews, 2017–2024 (pqac-00000001, pqac-00000002) | Cryptorchidism; inguinal hernia; transverse testicular ectopia; uterus/fallopian-tube/upper-vaginal remnants; normal male external genitalia |
| Diagnosis | Suspect PMDS in bilateral cryptorchidism, transverse testicular ectopia, or an inguinal hernia containing uterus-like tissue. Evaluation combines examination, ultrasonography/MRI, 46,XY karyotype, serum AMH, laparoscopy/pathology, and AMH/AMHR2 sequencing with copy-number analysis when needed. | In a 2022 study, 3 of 11 unrelated cryptorchidism patients had biallelic AMH/AMHR2 variants. MRI demonstrated Müllerian remnants in all three. | Human molecular case series, January 2022 (pqac-00000006, pqac-00000007) | Diagnostic procedures: pelvic ultrasound, pelvic MRI, laparoscopy, karyotype, serum AMH, germline sequencing, CNV analysis, histopathology |
| Biomarkers | Very low or undetectable AMH supports AMH deficiency; normal or elevated AMH supports AMHR2 resistance, but age- and assay-specific interpretation is essential. Testosterone is generally preserved because Leydig-cell androgen production is not the primary defect. | Example AMH values in a 2022 series: 0.06, 3.21, and 7.72 ng/mL; the 2024 AMHR2 p.Ile349Thr case had age-appropriate AMH. | Human case series/case report, 2022 and 2024 (pqac-00000007, pqac-00000008, pqac-00000016) | Biomarkers: anti-Müllerian hormone, testosterone, inhibin B, LH, FSH; genotype–biomarker correlation |
| Malignancy / fertility | Cancer risk is driven mainly by undescended testes; malignant transformation of Müllerian remnants is reported but less frequent. Fertility is uncommon but possible if at least one testis is scrotal and its excretory ducts remain intact. | Testicular malignant degeneration was reported in 33% of adults in a selected 157-case experience; other literature estimates range from 3.1–8.4% to 5–18%. Approximately 19% reportedly fathered a child naturally. | Human referral cohort and literature reviews, 2017–2022 (pqac-00000005, pqac-00000006, pqac-00000010, pqac-00000011) | Complications: testicular neoplasm, Müllerian-remnant neoplasm, azoospermia, oligospermia, male infertility |
| Management | Management is individualized: early orchiopexy when feasible, careful laparoscopic assessment, and selective subtotal/complete resection or retention of Müllerian remnants. Preservation of the vas deferens and testicular blood supply takes priority; retained remnants require surveillance. | In a 12-patient Chinese series, 8 underwent orchiopexy with uterine preservation; 3 later developed remnant cysts. Three underwent subtotal hysterectomy; one sustained vas deferens injury and one postoperative hemorrhage. | Human surgical cohort, 2022 (pqac-00000003) | Interventions: orchiopexy, laparoscopy, hysterectomy/remnant excision, orchidectomy when indicated, fertility preservation, imaging surveillance |
| 2024 advances | A previously unreported homozygous AMHR2 kinase-domain variant was associated with PMDS and supernumerary testes. Biochemical research also mapped AMH residues involved in type-I and type-II receptor interactions and improved precursor processing, refining understanding of receptor-complex assembly. | AMHR2 NM_020547.3:c.1046T>C (p.Ile349Thr), classified likely pathogenic; engineered AMH variants increased potency approximately 5- to 10-fold in vitro. | Human case report/review and experimental protein study, November–December 2024 (pqac-00000008, pqac-00000016) | AMHR2 protein-kinase domain; AMH processing; ligand–receptor binding; TGF-β/BMP-family signaling |
| Mouse model | Homozygous Amh- or Amhr2-null male mice retain uterus, oviducts, and partial vagina despite normal testes and Wolffian derivatives, recapitulating the core human developmental lesion. Progressive seminiferous epithelial atrophy models downstream subfertility. | Amhr2-null males sired offspring at less than a 50% rate; focal tubular atrophy appeared by 2 months and markedly impaired spermatogenesis by 9 months. | Targeted knockout model/review, 2019 (pqac-00000009) | Model: Amh knockout, Amhr2 knockout; phenotypes: persistent Müllerian structures, testicular atrophy, reduced male fertility |
| Canine natural disease | Miniature Schnauzers have sex-limited autosomal-recessive PMDS caused by AMHR2 c.241C>T (p.Arg81*); affected XY dogs retain oviducts, uterus, cervix, and cranial vagina and may have cryptorchidism. | Among 216 North American Miniature Schnauzers, mutant-allele frequency was 0.16 and carrier frequency 0.27; approximately 50% of affected dogs had unilateral or bilateral cryptorchidism. | Natural veterinary cohort and comparative review, 2018–2019 (pqac-00000009, pqac-00000012) | Species: dog; breed: Miniature Schnauzer; gene: AMHR2; variant: c.241C>T (p.Arg81*); autosomal recessive, sex limited |
| Canine 2024 genomics | Recent comparative analysis identified technical blind spots in canine PMDS sequencing: GC-rich repetitive AMH exon 5 has poor coverage, and AMHR2 annotation differs among canine genome assemblies. Targeted resequencing may resolve genetically unexplained cases in other breeds. | CanFam3.1 represented 11 AMHR2 coding exons with complete deep coverage; ROS_Cfam_1.0 represented only 8. | Computational genomics preprint, posted December 4, 2024 (pqac-00000013, pqac-00000014, pqac-00000015) | Comparative genomics; AMH exon 5; AMHR2 structural annotation; targeted resequencing |


*Table: Concise evidence matrix covering PMDS definition, genetics, clinical features, diagnosis, outcomes, management, recent advances, and comparative models. Quantitative estimates are tied to their underlying evidence type and should be interpreted cautiously because most human data derive from rare-disease referral cohorts and case series.*