Von Hippel-Lindau disease (vHL) is a hereditary tumor predisposition syndrome that places affected individuals at risk for multiple tumors, which are predominantly benign and generally occur in the central nervous system or abdomen. Although the majority of tumors occur in adults, children and adolescents with the condition develop a significant proportion of vHL manifestations and are vulnerable to delayed tumor detection and their sequelae. Although multiple tumor screening paradigms are currently being utilized for patients with vHL, surveillance should be reassessed as the available relevant clinical information continues to expand. We propose a new vHL screening paradigm similar to existing approaches, with important modifications for some tumor types, placing an emphasis on risks in childhood. This includes advancement in the timing of surveillance initiation and increased frequency of screening evaluations. Another neuroendocrine-related familial condition is the rapidly expanding hereditary paraganglioma and pheochromocytoma syndrome (HPP). The tumor spectrum for patients with HPP syndrome includes paragangliomas, pheochromocytomas, renal cancer, and gastrointestinal stromal tumors. The majority of patients with HPP syndrome harbor an underlying variant in one of the SHDx genes (SDHA, SDHB, SDHC, SDHD, SDHA, and SDHAF2), although other genes also have been described (MAX and TMEM127). Annual screening for elevated plasma or urine markers along with complete blood count and biennial whole-body MRI accompanied by focal neck MRI is recommended for older children and adults with HPP syndrome to detect tumors early and to decrease morbidity and mortality from HPP-related tumors.

A number of genetic syndromes have been linked to increased risk for Wilms tumor (WT), hepatoblastoma (HB) and other embryonal tumors. Here, we outline these rare syndromes with at least a 1% risk to develop these tumors and recommend uniform tumor screening recommendations for North America. Specifically, for syndromes with increased risk for WT, we recommend renal ultrasounds every 3 months from birth (or the time of diagnosis) through the 7th birthday. For HB, we recommend screening with full abdominal ultrasound and alpha-fetoprotein serum measurements every 3 months from birth (or the time of diagnosis) through the 4th birthday. We recommend that when possible, these patients be evaluated and monitored by cancer predisposition specialists. At this time, these recommendations are not based on the differential risk between different genetic or epigenetic causes for each syndrome, which some European centers have implemented. This differentiated approach largely represents distinct practice environments between the United States and Europe and these guidelines are designed to be a broad framework within which physicians and families can work together to implement specific screening. Further study is expected to lead to modifications of these recommendations.