| #613325 | ||||||||||
| RHABDOID TUMOR PREDISPOSITION SYNDROME 2; RTPS2 | ||||||||||
| Phenotype Gene Relationships | ||||||||||
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| TEXT | ||||||||||
| A number sign (#) is used with this entry because rhabdoid tumor predisposition syndrome-2 (RTPS2) is caused by heterozygous germline mutation in the SMARCA4 gene (603254) on chromosome 19p. RTPS1 (609322) is caused by mutation in the SMARCB1 gene (601607) on chromosome 22q11. | ||||||||||
| Clinical Features | ||||||||||
| Schneppenheim et al. (2010) reported 2 German sisters with highly aggressive malignant embryonal tumors of the brain. At age 8 months, the first girl was found to have a mass originating from the right cerebellopontine angle involving the brainstem. She died a few weeks later. Her sister presented at 7 months of age with increased abdominal circumference and pain. Although imaging studies suggested a stage IV Wilms tumor (194070) with metastases to the lungs and mediastinum, neuropathologic analysis showed a rhabdoid tumor. She died at 18 months of distant and local disease. Neuropathology of both tumors showed a SMARCB1-expressive atypical teratoid/rhabdoid tumor. | ||||||||||
| Molecular Genetics | ||||||||||
| By candidate gene sequencing in 2 German sisters with early-onset fatal rhabdoid tumors, Schneppenheim et al. (2010) identified a heterozygous germline truncating mutation in the SMARCA4 gene (R1189X; 603254.0001). The girls' unaffected father was heterozygous for the germline R1189X mutation, indicating reduced penetrance. Analysis of tumor tissue showed complete loss of SMARCA4 expression and loss of heterozygosity at the SMARCA4 locus. SNP array analysis indicated that partial uniparental disomy of the paternal allele was the cause of LOH in the tumors. Schneppenheim et al. (2010) noted both SMARCA4 and the tumor suppressor SMARCB1 are members of the ATP-dependent SWI/SNF chromatin-remodeling complex. | ||||||||||
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