Syndromes Flashcards
Foundations
Carney triad
characterized by the coexistence of three types of neoplasms, mainly in young women, including gastric gastrointestinal stromal tumor, pulmonary chondroma, and extra-adrenal paraganglioma. The underlying genetic defect remains elusive. CT is distinct from Carney complex, and the Carney-Stratakis syndrome.
Carney triad
named for J Aidan Carney, is considered to be a specific type of multiple endocrine neoplasia (MEN). The three classically associated tumors are a subset of gastric epithelioid leiomyosarcoma (it is now known that this subset is actually gastrointestinal stromal tumor arising from the interstitial cells of Cajal), pulmonary chondroma, and extra-adrenal paraganglioma.
the gastrointestinal stromal tumors (GIST) in Carney triad
GIST in Carney triad lack CD117 (c-kit) mutations (i.e., they are wild-type), and hence these GISTs may prove unresponsive to Imatinib.
Carney triad
The condition manifests more commonly in females. Multiple tumors in multiple organs in young patients, with occasional sibling involvement, suggested an inherited disorder, but the underlying genetic basis has not been identified.
In addition to these three classical tumors, there is an increased incidence of pheochromocytoma, esophageal leiomyoma and adrenocortical adenoma.
Carney complex
characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue nevus.
Carney–Stratakis syndrome
describes the dyad of hereditary gastrointestinal stromal tumor (GIST) and paraganglioma, that is caused by germline mutations in the mitochondrial tumor suppressor gene pathway involving the succinate dehydrogenase subunits SDHD, SDHC and SDHB.
SDHB immunohistochemistry and SDH-x genetic analysis
Taken together, SDHB immunohistochemistry and SDH-x genetic analysis should be viewed as complementary tests. In cases of strong clinical suspicion, follow-up mutational analysis should be considered despite retention of SDHB expression.
Behçet syndrome
an auto-inflammatory systemic vasculitis of unknown etiology. It is characterized by mucocutaneous manifestations, including recurrent oral and genital ulcerations, ocular manifestations, especially chronic relapsing uveitis, and systemic vasculitis involving arteries and veins of all sizes.
Felty’s syndrome
a rare autoimmune disease characterized by the triad of rheumatoid arthritis, enlargement of the spleen and low neutrophil count.
Alport syndrome
defined as hereditary nephritis often associated with sensorineural hearing loss and ocular abnormalities, along with macro-thrombocytic thrombocytopenia.
Giant platelets and thrombocytopenia are seen on the peripheral smear.
Wiskott-Aldrich syndrome
rare X-linked disorder with a characteristic triad of immunodeficiency, thrombocytopenia, and eczema. It results from a genetic mutation in the gene encoding Wiskott-Aldrich syndrome protein (WASp) affecting the immune system and inducing a state of immunodeficiency. The disease follows a broad spectrum depending on gene mutations ranging from severe phenotype (classic WAS) to milder ones (X-linked thrombocytopenia (XLT) and X-linked neutropenia)
Wiskott-Aldrich syndrome an X-linked genetic defect gene location?
short arm of the X-chromosome at Xp 11.22-23 position. The gene product Wiskott-Aldrich protein (WASp) is a 502 amino acid protein expressed in the cytoplasm of non-erythroid hematopoietic cells. More than 300 gene mutations have been identified leading to impaired protein configuration. The most common mutations are missense mutations followed by non-sense, splice site and short deletion mutations. Because of the wide range of genetic mutations, the disease itself has phenotypic variability ranging from severe (classic WAS) to mild disease X linked thrombocytopenia and X linked neutropenia.
three main clinical phenotypic manifestations of Wiskott-Aldrich syndrome
Classic (severe) Wiskott-Aldrich syndrome: This is the severe phenotype of WAS. Affected boys present in early childhood with a hemorrhagic diathesis due to thrombocytopenia; recurrent bacterial, viral and fungal infections; and extensive eczema. Lymphadenopathy is frequently present, especially in those WAS patients with chronic eczema, and hepatosplenomegaly is common. Patients with classic WAS tend to develop autoimmune disorders and lymphoma or other malignancies, often leading to early death.[11]
X-linked neutropenia (XLN): XLN presents mainly as congenital neutropenia. Patients with XLN present with infections characteristic for neutropenia but may also develop infections associated with lymphocyte dysfunction. These patients also have an elevated risk for myelodysplasia.[12]
X-linked thrombocytopenia (XLT): XLT presents as congenital thrombocytopenia that is sometimes intermittent (IXLT).[13] Eczema is usually mild. These patients generally have a benign disease course and good long-term survival. They still carry an increased risk (lower than that for WAS) for severe events such as life-threatening infections (especially post-splenectomy), serious hemorrhage, autoimmune complications, and cancer.[14] Any male with thrombocytopenia and small platelets should be evaluated for WASp expression and WAS gene mutations.
Size of platelet volume is Wiskott-Aldrich syndrome?
The usual size is less than 6 fl (normal 7.5 to 10.5 fl). However, rarely, normal-sized platelets or large platelets have been reported.
eczema-thrombocytopenia-immunodeficiency syndrome
Wiskott–Aldrich syndrome (WAS)
