{"id":27157,"date":"2024-05-26T15:06:34","date_gmt":"2024-05-26T13:06:34","guid":{"rendered":"https:\/\/www.krebs-praedisposition.de\/?post_type=kompendium&p=27157"},"modified":"2025-08-26T13:21:11","modified_gmt":"2025-08-26T11:21:11","slug":"retinoblastoma-predisposition","status":"publish","type":"kompendium","link":"https:\/\/www.krebs-praedisposition.de\/en\/kompendium\/retinoblastoma-predisposition\/","title":{"rendered":"Retinoblastoma Predisposition"},"content":{"rendered":"

Retinoblastoma Predisposition \u2013\u00a0Definition<\/h2><\/div>
<\/div><\/div><\/div><\/div>

Retinoblastoma (OMIM #180200) is a malignant tumor of the immature retina that is based on pathogenic variants in both alleles of the RB1<\/em> gene and usually occurs before the age of 5. The tumor can occur unilaterally or bilaterally. The hereditary form of retinoblastoma also predisposes to primitive neuroectodermal tumors, the most common of which is pineoblastoma. There is also an increased risk of developing secondary tumors such as osteosarcomas and other soft tissue sarcomas, tumors of the nasal cavity, eye and orbit, melanomas, and brain tumors.<\/p>\n<\/div>

Synonym:<\/p>\n<\/div><\/div><\/div>

–<\/p>\n<\/div><\/div><\/div><\/div>

<\/div><\/div>

Gene:<\/p>\n<\/div><\/div><\/div>

RB1<\/em><\/p>\n

in 1.5% of cases with isolated unilateral retinoblastoma: MYCN<\/em> amplification<\/p>\n<\/div><\/div><\/div><\/div>

<\/div><\/div>

Gen\u00ade product:<\/p>\n<\/div><\/div><\/div>

RB1<\/p>\n<\/div><\/div><\/div><\/div>

<\/div><\/div>

Function:<\/p>\n<\/div><\/div><\/div>

ubiquitous nuclear phosphoprotein involved in cell cycle regulation (transition from G1 to S phase)<\/p>\n<\/div><\/div><\/div><\/div>

<\/div><\/div>

Pattern of inheritance:<\/p>\n<\/div><\/div><\/div>

Autosomal dominant<\/p>\n

40% of retinoblastomas are hereditary.<\/p>\n

80% of hereditary retinoblastomas are de novo<\/i> mutations.<\/p>\n<\/div><\/div><\/div><\/div>

<\/div><\/div>

Prevalence:<\/p>\n<\/div><\/div><\/div>

Incidence about 1:15,000-1:20,000 live births;<\/p>\n

Incidence rate 3-5 per 1 million<\/p>\n<\/div><\/div><\/div><\/div>

<\/div><\/div>

Genotype-phenotype correlation:<\/p>\n<\/div><\/div><\/div>

Nonsense and frameshift mutations in exons 2 to 25 (the most common a pathogenic variants with familial occurrence) almost always lead to bilateral retinoblastomas with high penetrance.<\/p>\n

Lower penetrance with variable expressivity is present in missense, promoter, and splice mutations.<\/p>\n

Patients with a pathogenic variants of lower penetrance also show a lower risk of developing secondary tumors.<\/p>\n

Patients with complete 13q deletion have the same outcome for retinoblastoma, and pineoblastomas also occur. In addition, these patients exhibit facial dysmorphia (anteverted ears, broad forehead, long philtrum) and varying degrees of neurological impairment.<\/p>\n<\/div><\/div><\/div><\/div>

<\/div><\/div>

Penetrance:<\/p>\n<\/div><\/div><\/div>

90-95% for most a pathogenic variants<\/p>\n<\/div><\/div><\/div><\/div><\/div><\/div>

<\/div>
<\/div><\/div><\/div><\/div><\/div><\/div>

Overview of the Chapters on This Page:<\/h4><\/div><\/div><\/div>