MedGen

Kury-Isidor syndrome (KURIS) is a neurodevelopmental disorder with a highly variable phenotype. It is characterized mainly by mild global developmental delay apparent from infancy or early childhood with walking delayed by a few years and speech delay, often with language deficits. Intellectual development may be mildly delayed, borderline, or even normal; most patients have behavioral problems, including autism. Additional variable systemic features may include poor overall growth, hypotonia, distal skeletal anomalies, seizures, and nonspecific dysmorphic facial features (summary by Kury et al., 2022). [from OMIM]

BAP1 tumor predisposition syndrome (BAP1-TPDS) is associated with an increased risk for a specific skin lesion, BAP1-inactivated melanocytic tumors (BIMT; formerly called atypical Spitz tumors), and the following cancers, in descending order of frequency: uveal (eye) melanoma (UM), malignant mesothelioma (MMe), cutaneous melanoma (CM), renal cell carcinoma (RCC), and basal cell carcinoma (BCC). Hepatocellular carcinoma, cholangiocarcinoma, and meningioma may also be associated with BAP1-TPDS. Affected individuals can have more than one type of primary cancer. In general, the median age of onset of these tumors is younger than in the general population. UM tends to be a more aggressive class 2 tumor with higher risk for metastasis and reduced survival compared to UM occurring in the general population. Due to the limited number of families reported to date, the penetrance, natural history, and frequencies of BAP1-associated tumors are yet to be determined. Other suspected but unconfirmed tumors in BAP1-TPDS include (in alphabetic order): breast cancer, neuroendocrine carcinoma, non-small-cell lung adenocarcinoma, thyroid cancer, and urinary bladder cancer. [from GeneReviews]

Uveal melanoma (see 155720) is the most common primary intraocular malignancy. Metastases arise in more than 30% of patients, usually to the liver, with a poor prognosis (median survival of 10 months) (summary by Derrien et al., 2021). Somatic monosomy 3, which is an unusual finding in most tumors, is present in approximately 50% of uveal melanomas and is significantly correlated with metastatic disease (summary by Tschentscher et al., 2001). Mutation in the BAP1 gene is known to confer susceptibility to this specific disease. It has been estimated that about 22% of cases of familial uveal melanoma are due to BAP1 mutations. Conversely, uveal melanoma has been reported in about 31% of BAP1 mutation carriers, making it one of the most common manifestations of TPDS1 (Rai et al., 2016; Rai et al., 2017). For a discussion of genetic heterogeneity of susceptibility to uveal melanoma, see UVM1 (606660), caused by mutation in the MBD4 gene (603574) on chromosome 3q21. [from OMIM]