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Frasier syndrome

MedGen UID:
215533
Concept ID:
C0950122
Disease or Syndrome
Synonyms: Frasier Syndrome; Syndrome, Frasier
SNOMED CT: Frasier syndrome (445431000)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): WT1 (11p13)
 
Monarch Initiative: MONDO:0007635
OMIM®: 136680
Orphanet: ORPHA347

Authors:

Additional descriptions

From OMIM
Frasier syndrome is a rare disorder defined by pseudohermaphroditism and progressive glomerulopathy (Frasier et al., 1964; Haning et al., 1985; Kinberg et al., 1987). Patients present with normal female external genitalia, streak gonads, and XY karyotype, and frequently develop gonadoblastoma (Blanchet et al., 1977). Glomerular symptoms consist of childhood proteinuria and nephrotic syndrome, characterized by nonspecific focal and segmental glomerular sclerosis, progressing to end-stage renal failure in adolescence or early adulthood. Wilms tumor is not a usual feature (Barbaux et al., 1997).  http://www.omim.org/entry/136680
From MedlinePlus Genetics
Frasier syndrome is a condition that affects the kidneys and genitalia.

Frasier syndrome is characterized by kidney disease that begins in early childhood. Affected individuals have a condition called focal segmental glomerulosclerosis, in which scar tissue forms in some glomeruli, which are the tiny blood vessels in the kidneys that filter waste from blood. In people with Frasier syndrome, this condition often leads to kidney failure by adolescence.

Although males with Frasier syndrome have the typical male chromosome pattern (46,XY), they have gonadal dysgenesis, in which external genitalia do not look clearly male or clearly female or the genitalia appear female-typical. The internal reproductive organs (gonads) are typically undeveloped and referred to as streak gonads. These abnormal gonads are nonfunctional and often become cancerous, so they are usually removed surgically early in life.

Affected females usually have normal genitalia and gonads and have only the kidney features of the condition. Because they do not have all the features of the condition, females are usually given the diagnosis of isolated nephrotic syndrome.  https://medlineplus.gov/genetics/condition/frasier-syndrome

Clinical features

From HPO
Ovarian gonadoblastoma
MedGen UID:
309510
Concept ID:
C1518716
Neoplastic Process
The presence of a gonadoblastoma of the ovary.
Focal segmental glomerulosclerosis
MedGen UID:
4904
Concept ID:
C0017668
Disease or Syndrome
Segmental accumulation of scar tissue in individual (but not all) glomeruli.
Gonadal dysgenesis
MedGen UID:
9075
Concept ID:
C0018051
Congenital Abnormality
Gonadal dysgenesis is the name given to any of a multitude of conditions that can cause impaired development of the gonads, i.e., the testes or ovaries, or to the related phenotypic features. The term is to be avoided if possible for new annotations, and more specific terms should be chosen.
Nephrotic syndrome
MedGen UID:
10308
Concept ID:
C0027726
Disease or Syndrome
Nephrotic syndrome is a collection of findings resulting from glomerular dysfunction with an increase in glomerular capillary wall permeability associated with pronounced proteinuria. Nephrotic syndrome refers to the constellation of clinical findings that result from severe renal loss of protein, with Proteinuria and hypoalbuminemia, edema, and hyperlipidemia.
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Primary amenorrhea
MedGen UID:
115918
Concept ID:
C0232939
Disease or Syndrome
Abnormally late or absent menarche in a female with normal secondary sexual characteristics.
Male pseudohermaphroditism
MedGen UID:
68666
Concept ID:
C0238395
Congenital Abnormality
Hermaphroditism refers to a discrepancy between the morphology of the gonads and that of the external genitalia. In male pseudohermaphroditism, the genotype is male (XY) and the external genitalia are imcompletely virilized, ambiguous, or complete female. If gonads are present, they are testes.
Stage 5 chronic kidney disease
MedGen UID:
384526
Concept ID:
C2316810
Disease or Syndrome
A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFrasier syndrome
Follow this link to review classifications for Frasier syndrome in Orphanet.

Professional guidelines

PubMed

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
Auber F, Jeanpierre C, Denamur E, Jaubert F, Schleiermacher G, Patte C, Cabrol S, Leverger G, Nihoul-Fékété C, Sarnacki S
Pediatr Blood Cancer 2009 Jan;52(1):55-9. doi: 10.1002/pbc.21759. PMID: 18816692
Auber F, Lortat-Jacob S, Sarnacki S, Jaubert F, Salomon R, Thibaud E, Jeanpierre C, Nihoul-Fékété C
J Pediatr Surg 2003 Jan;38(1):124-9; discussion 124-9. doi: 10.1053/jpsu.2003.50025. PMID: 12592634

Recent clinical studies

Etiology

Lopez-Gonzalez M, Ariceta G
Pediatr Nephrol 2024 Sep;39(9):2601-2609. Epub 2024 Feb 7 doi: 10.1007/s00467-024-06302-y. PMID: 38326647
Kollios K, Karipiadou A, Papagianni M, Traeger-Synodinos J, Kosta K, Savvidou P, Stabouli S, Roilides E
J Pediatr Hematol Oncol 2022 Nov 1;44(8):471-473. Epub 2022 Jun 8 doi: 10.1097/MPH.0000000000002501. PMID: 35700406
Mestrallet G, Bertholet-Thomas A, Ranchin B, Bouvier R, Frappaz D, Cochat P
Pediatr Transplant 2011 May;15(3):e53-5. doi: 10.1111/j.1399-3046.2010.01273.x. PMID: 20408995
Al-Mulhim AN, Kamal HM
East Mediterr Health J 2010 Feb;16(2):214-7. PMID: 20799577
Moorthy AV, Chesney RW, Lubinsky M
Am J Med Genet Suppl 1987;3:297-302. doi: 10.1002/ajmg.1320280535. PMID: 3130865

Diagnosis

Lopez-Gonzalez M, Ariceta G
Pediatr Nephrol 2024 Sep;39(9):2601-2609. Epub 2024 Feb 7 doi: 10.1007/s00467-024-06302-y. PMID: 38326647
Ezaki J, Hashimoto K, Asano T, Kanda S, Akioka Y, Hattori M, Yamamoto T, Shibata N
Cancer Prev Res (Phila) 2015 Apr;8(4):271-6. Epub 2015 Jan 26 doi: 10.1158/1940-6207.CAPR-14-0415. PMID: 25623218
Mestrallet G, Bertholet-Thomas A, Ranchin B, Bouvier R, Frappaz D, Cochat P
Pediatr Transplant 2011 May;15(3):e53-5. doi: 10.1111/j.1399-3046.2010.01273.x. PMID: 20408995
Al-Mulhim AN, Kamal HM
East Mediterr Health J 2010 Feb;16(2):214-7. PMID: 20799577
Jaubert F, Vasiliu V, Patey-Mariaud de Serre N, Auber F, Jeanpierre C, Gubler MC, Nihoul-Fékété C, Fellous M
Arkh Patol 2003 Mar-Apr;65(2):40-4. PMID: 15357247

Therapy

Kollios K, Karipiadou A, Papagianni M, Traeger-Synodinos J, Kosta K, Savvidou P, Stabouli S, Roilides E
J Pediatr Hematol Oncol 2022 Nov 1;44(8):471-473. Epub 2022 Jun 8 doi: 10.1097/MPH.0000000000002501. PMID: 35700406
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
Peco-Antić A, Ozaltin F, Parezanović V, Milosevski-Lomić G, Zdravković V
Srp Arh Celok Lek 2013 Sep-Oct;141(9-10):685-8. doi: 10.2298/sarh1310685p. PMID: 24364235
Stefanidis CJ, Querfeld U
Eur J Pediatr 2011 Nov;170(11):1377-83. Epub 2011 Feb 8 doi: 10.1007/s00431-011-1397-6. PMID: 21298518
Sinha A, Sharma S, Gulati A, Sharma A, Agarwala S, Hari P, Bagga A
Pediatr Nephrol 2010 Oct;25(10):2171-4. Epub 2010 Apr 24 doi: 10.1007/s00467-010-1518-x. PMID: 20419325

Prognosis

Ezaki J, Hashimoto K, Asano T, Kanda S, Akioka Y, Hattori M, Yamamoto T, Shibata N
Cancer Prev Res (Phila) 2015 Apr;8(4):271-6. Epub 2015 Jan 26 doi: 10.1158/1940-6207.CAPR-14-0415. PMID: 25623218
Mestrallet G, Bertholet-Thomas A, Ranchin B, Bouvier R, Frappaz D, Cochat P
Pediatr Transplant 2011 May;15(3):e53-5. doi: 10.1111/j.1399-3046.2010.01273.x. PMID: 20408995
Melo KF, Martin RM, Costa EM, Carvalho FM, Jorge AA, Arnhold IJ, Mendonca BB
J Clin Endocrinol Metab 2002 Jun;87(6):2500-5. doi: 10.1210/jcem.87.6.8521. PMID: 12050205
Bönte A, Schröder W, Denamur E, Querfeld U
Nephrol Dial Transplant 2000 Oct;15(10):1688-90. doi: 10.1093/ndt/15.10.1688. PMID: 11007843
Koziell A, Charmandari E, Hindmarsh PC, Rees L, Scambler P, Brook CG
Clin Endocrinol (Oxf) 2000 Apr;52(4):519-24. doi: 10.1046/j.1365-2265.2000.00980.x. PMID: 10762296

Clinical prediction guides

Inoue S, Kondo A, Inoki Y, Ichikawa Y, Tanaka Y, Ueda C, Kitakado H, Suzuki R, Okada E, Sakakibara N, Horinouchi T, Nozu K
Clin Exp Nephrol 2024 Nov;28(11):1075-1081. Epub 2024 Jun 14 doi: 10.1007/s10157-024-02510-w. PMID: 38877226Free PMC Article
Torban E, Goodyer P
Am J Physiol Renal Physiol 2024 Jan 1;326(1):F3-F19. Epub 2023 Nov 2 doi: 10.1152/ajprenal.00248.2023. PMID: 37916284
Yang C, Romaniuk PJ
Biochem Cell Biol 2008 Aug;86(4):312-21. doi: 10.1139/o08-075. PMID: 18756326
Niaudet P, Gubler MC
Pediatr Nephrol 2006 Nov;21(11):1653-60. Epub 2006 Aug 23 doi: 10.1007/s00467-006-0208-1. PMID: 16927106
Jaubert F, Vasiliu V, Patey-Mariaud de Serre N, Auber F, Jeanpierre C, Gubler MC, Nihoul-Fékété C, Fellous M
Arkh Patol 2003 Mar-Apr;65(2):40-4. PMID: 15357247

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