FS
MCID: FRS002
MIFTS: 54
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Frasier Syndrome (FS)
Categories:
Cancer diseases, Endocrine diseases, Fetal diseases, Genetic diseases, Nephrological diseases, Rare diseases, Reproductive diseases
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MalaCards integrated aliases for Frasier Syndrome:Characteristics:Orphanet epidemiological data:58
frasier syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; OMIM®:57 (Updated 05-Mar-2021)
Inheritance:
somatic mutation autosomal dominant
Miscellaneous:
phenotypic overlap with denys-drash syndrome . HPO:31Classifications:
MalaCards categories:
Global: Genetic diseases Rare diseases Fetal diseases Cancer diseases Anatomical: Nephrological diseases Reproductive diseases Endocrine diseases
ICD10:
33
Orphanet: 58
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GARD :
20
The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 347DefinitionA rare genetic, syndromic glomerular disorder characterized by the association of progressive glomerular nephropathy and 46,XY complete gonadal dysgenesis with a high risk of developing gonadoblastoma.EpidemiologyTo date, less than 150 cases have been described.Clinical descriptionNephropathy is the hallmark of the disease. It develops during childhood presenting as persistent proteinuria and subsequently steroid-resistant nephrotic syndrome (SRNS) and progresses to end-stage renal disease (ESRD) in the second or third decade of life. On renal biopsy, focal segmental glomeruloscrelosis (FSGS) is the most common histopathological finding. Individuals have a 46, XY karyotype and present with female external genitalia, complete gonadal dysgenesis and have a higher risk of gonadoblastoma. These individuals are later evaluated for delayed puberty or primary amenorrhea. Since (modest) breast development occurs also without estrogen stimulus, failure to recognize a delayed puberty is not rare. In addition, the clinical picture may be confused by attributing pubertal delay to previous immunosuppressive therapy, renal insufficiency itself or renal transplantation. Complete gonadal dysgenesis results in infertility, female external genitalia and presence of Mullerian structures. Wilms tumor is not common in individuals with Frasier syndrome.EtiologyFrasier syndrome has been associated to specific pathogenic variants affecting nucleotides 4-5 of the intron 9 (previously referred to as IVS9+4; IVS9+5) in the WT1 gene (11p13). WT1 encodes for a protein that serves as regulatory transcription factor important both for renal and gonadal development.Diagnostic methodsThe diagnosis is suspected on childhood onset of progressive glomerulopathy with findings of FSGS on histological analysis. Phenotypic females with delayed puberty or primary amenorrhea, should be carefully evaluated for signs of nephropathy. When the clinical findings suggest the diagnosis of WT1 associated disorders, single gene testing of the hotspot 8-9 exons with adjacent introns can be performed. Karyotype testing is recommended for all individuals with WT1 intron 9 pathogenic variants.Differential diagnosisThe main differential diagnosis is idiopathic steroid-resistant nephrotic syndrome, and other WT1 associated diseases including Denys-Drash syndrome, genetic steroid resistant nephrotic syndrome and disorders of testicular development.Genetic counselingMost affected individuals have a de novo pathogenic variant and hence negative family history; however, autosomal dominant inheritance has been reported. Where karyotyping is indicated, pre-testing genetic counselling on the possibility of detecting sex reversal should be offered.Management and treatmentManagement is multidisciplinary and should involve a nephrologist for management of chronic renal failure (initially with nephroprotective medical therapy and afterwards with renal replacement therapies or transplantation when ESRD occurs), an endocrinologists for treatment of associated disorder of testicular development, and oncologists and surgeons to evaluate the need for an early gonadectomy in order to prevent tumorigenesis. Preemptive bilateral gonadectomy at the time of renal transplant or placement of a peritoneal dialysis catheter might be an option.PrognosisThere is limited information on life expectancy. After kidney transplantation, nephrotic syndrome does not recur. 46,XY individuals with complete gonadal dysgenesis are infertile.Visit the Orphanet disease page for more resources.
MalaCards based summary : Frasier Syndrome, also known as fs, is related to gonadoblastoma and pseudohermaphroditism. An important gene associated with Frasier Syndrome is WT1 (WT1 Transcription Factor), and among its related pathways/superpathways are Embryonic and Induced Pluripotent Stem Cell Differentiation Pathways and Lineage-specific Markers and Primary Focal Segmental Glomerulosclerosis FSGS. Affiliated tissues include Kidney, ovary and pituitary, and related phenotypes are glomerulopathy and male pseudohermaphroditism Disease Ontology : 12 A syndrome that is characterized by gonadal dysgenesis, streak gonads, progressive focal segmental glomerulonephropathy and the development of urogenital cancers that is the result of mutation in the WT1 gene. MedlinePlus Genetics : 43 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 (ambiguous genitalia) or the genitalia appear completely female. 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. OMIM® : 57 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). (136680) (Updated 05-Mar-2021) UniProtKB/Swiss-Prot : 73 Frasier syndrome: Characterized by a slowly progressing nephropathy leading to renal failure in adolescence or early adulthood, male pseudohermaphroditism, and no Wilms tumor. As for histological findings of the kidneys, focal glomerular sclerosis is often observed. There is phenotypic overlap with Denys-Drash syndrome. Inheritance is autosomal dominant. Wikipedia : 74 Frasier syndrome is a urogenital anomaly associated with the WT1 (Wilms tumor 1 gene)... more... |
Human phenotypes related to Frasier Syndrome:58 31 (show all 19)
Symptoms via clinical synopsis from OMIM®:57 (Updated 05-Mar-2021)Clinical features from OMIM®:136680 (Updated 05-Mar-2021)MGI Mouse Phenotypes related to Frasier Syndrome:46
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Interventional clinical trials:
Cochrane evidence based reviews: frasier syndrome |
MalaCards organs/tissues related to Frasier Syndrome:40
Kidney,
Ovary,
Pituitary
![]() Data from LifeMap, the Embryonic Development and Stem Cells Database
Cells/anatomical compartments in embryo or adult related to Frasier Syndrome:
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Articles related to Frasier Syndrome:(show top 50) (show all 125)
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ClinVar genetic disease variations for Frasier Syndrome:6 (show top 50) (show all 431)
UniProtKB/Swiss-Prot genetic disease variations for Frasier Syndrome:73
Copy number variations for Frasier Syndrome from CNVD:7
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Search
GEO
for disease gene expression data for Frasier Syndrome.
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Cellular components related to Frasier Syndrome according to GeneCards Suite gene sharing:
Biological processes related to Frasier Syndrome according to GeneCards Suite gene sharing:(show all 21)
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