Illness46XY - gonadal dysgenesis, differential diagnosis

NGS +

{Sanger]

Pure 46XY gonadal dysgenesis (GD) presents as phenotypically female, possibly with high stature, bilateral streak gonads, delayed puberty, amenorrhoea and small or normal Müller structures. If 46XY GD was not diagnosed at birth, delayed puberty and primary amenorrhoea are noticeable in adolescence. Patients rarely have tumour masses in the abdominal/pelvic area, but then often a gonadoblastoma. Occasionally 46XY GD may be linked to other syndromes. Patients with partial or mixed 46XY GD typically show different degrees of masculinisation of the external and internal genitalia at birth, depending on the proportion of testicular tissue, usually with female external genitalia and a certain degree of virilisation. Main criteria for the diagnosis of 46XY GD are appearance and histology of the gonads. As the risk of gonadoblastoma is increased in these patients, the exact diagnosis is made after prophylactic or therapeutic gonadectomy. Sequence analysis of the SRY and NR5A1 genes reveals mutations only in up to 30% of 46XY GD. Examination of other genes increases the percentage in differential diagnosis, especially examination of the MAP3K1 gene. All inheritance patterns are observed. An inconspicuous genetic finding does not mean a reliable exclusion of the clinical suspected diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK539886/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182188/

• Alias: 46,XY pure gonadal dysgenesis
• Alias: 46XY intersex
• Alias: 46XY sex reversal
• Alias: Pseudohermaphroditism
• Alias: Swyer syndrome
• Allelic: 46XX sex reversal 1 (SRY)
• Allelic: 46XX sex reversal 4 (NR5A1)
• Allelic: Acampomelic campomelic dysplasia (SOX9)
• Allelic: Adrenal hypoplasia, congenital (NR0B1)
• Allelic: Adrenocortical insufficiency (NR5A1)
• Allelic: Alpha-thalassemia/mental retardation syndrome (ATRX)
• Allelic: Apert syndrome (FGFR2)
• Allelic: Atrial septal defect 2 (GATA4)
• Allelic: Atrioventricular septal defect 4 (GATA4)
• Allelic: Beare-Stevenson cutis gyrata syndrome (FGFR2)
• Allelic: Bent bone dysplasia syndrome (FGFR2)
• Allelic: Campomelic dysplasia (SOX9)
• Allelic: Craniofacial-skeletal-dermatologic dysplasia (FGFR2)
• Allelic: Craniosynostosis, nonspecific (FGFR2)
• Allelic: Crouzon syndrome (FGFR2)
• Allelic: Developmental + epileptic encephalopathy 1 (ARX)
• Allelic: Developmental + epileptic encephalopathy 28 (WWOX)
• Allelic: Diaphragmatic hernia 3 (ZFPM2)
• Allelic: Hydranencephaly with abnormal genitalia (ARX)
• Allelic: Hypospadias 2, XL (MAMLD1)
• Allelic: Intellectual developmental disorder, X 29 (ARX)
• Allelic: Jackson-Weiss syndrome (FGFR2)
• Allelic: LADD syndrome (FGFR2)
• Allelic: Lissencephaly, XL 2 (ARX)
• Allelic: Mental retardation-hypotonic facies syndrome, XL (ATRX)
• Allelic: Mullerian aplasia + hyperandrogenism (WNT4)
• Allelic: Nephrotic syndrome, type 4 (WT1)
• Allelic: Neurodevelopm. disorder, brain anomalies with/-out vertebral/cardiac anomalies (DHX37)
• Allelic: Ovarian dysgenesis 8 (ESR2)
• Allelic: Partington syndrome (ARX)
• Allelic: Pfeiffer syndrome (FGFR2)
• Allelic: Premature ovarian failure 7 (NR5A1)
• Allelic: SERKAL: 46,XX SEx Reversal with dysgenesis of Kidney, Adrenals + Lungs syndrome (WNT4)
• Allelic: Saethre-Chotzen syndrome (FGFR2)
• Allelic: Scaphocephaly and Axenfeld-Rieger anomaly (FGFR2)
• Allelic: Scaphocephaly, maxillary retrusion, and mental retardation (FGFR2)
• Allelic: Spermatogenic failure 8 (NR5A1)
• Allelic: Spinocerebellar ataxia, AR 12 (WWOX)
• Allelic: Tetralogy of Fallot (GATA4)
• Allelic: Tetralogy of Fallot (ZFPM2)
• Allelic: Ventricular septal defect 1 (GATA4)
• Allelic: Wilms tumor, type 1 (WT1)
• 46XY disorder of sex development [MONDO:0020040] (ESR2)
• 46XY gonadal dysgenesis [guidelines] (STARD8)
• 46XY gonadal dysgenesis [guidelines] (ZNRF3)
• 46XY gonadal dysgenesis with minifascicular neuropathy (DHH)
• 46XY sex reversal 1 (SRY)
• 46XY sex reversal 11, testicular regression syndrome (DHX37)
• 46XY sex reversal 2, dosage-sensitive (NR0B1)
• 46XY sex reversal 3 (NR5A1)
• 46XY sex reversal 5 (CBX2)
• 46XY sex reversal 6 (MAP3K1)
• 46XY sex reversal 7 (DHH)
• 46XY sex reversal 9 (ZFPM2)
• Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis (FGFR2)
• CAKUTHED: Cong. Anom. Kidney/Urinary Tract syn. +/- Hear loss, abn. Ears or Development delay (PBX1)
• Campomelic dysplasia with autosomal sex reversal (SOX9)
• Denys-Drash syndrome (WT1)
• Frasier syndrome (WT1)
• Gender Assignment Gene Panel (MAMLD1)
• Gonadal dysgenesis [Lit.], Gender Assignment Gene Panel (DMRT1)
• Meacham syndrome (WT1)
• Nivelon-Nivelon-Mabille [Chondrodysplasia-pseudohermaphroditism] syndrome (HHAT)
• Proud syndrome, Corpus callosum, agenesis, with abnormal genitalia (ARX)
• Schizencephaly (EMX2)
• Skeletal anomalies, learning difficulty [guidelines] (SOX8)
• Sudden infant death with dysgenesis of the testes syndrome (TSPYL1)
• Testicular anomalies with/-out congenital heart disease (GATA4)