Birth incidence and prevalence of tumor‐prone syndromes: Estimates from a UK family genetic register service

Abstract

Autosomal dominantly inherited tumor-prone syndromes are a substantial health problem and are amenable to epidemiologic studies by combining cancer surveillance registries with a genetic register (GR)-based approach. Knowledge of the frequency of the conditions provides a basis for appropriate health-resources allocations. GRs for five tumor-prone syndromes were established in the Manchester region of North West England in 1989 and 1990. Mapping birth dates of affected individuals from families onto regional birth rates has allowed an estimate of birth incidence, disease prevalence, and de novo mutation rates. Disease prevalence in order of frequency were for neurofibromatosis type 1 (NF1): 1 in 4,560; familial adenomatous polyposis (FAP): 1 in 18,976; nevoid basal cell carcinoma [Gorlin syndrome (GS)]: 1 in 30,827; neurofibromatosis type 2 (NF2) 1 in 56,161; and von Hippel Lindau (VHL) 1 in 91,111. Best estimates for birth incidence were: 1 in 2,699; 1 in 8,619; 1 in 14,963, 1 in 33,000; and 1 in 42,987, respectively. The proportions due to de novo mutation were: 42% (NF1); 16% (FAP); 26% (GS); 56% (NF2); and 21% (VHL). Estimates for NF1, NF2, FAP, and VHL are in line with previous estimates, and we provide the first estimates of birth incidence and de novo mutation rate for GS.

Discovery of Rare Mutations in Autism: Elucidating Neurodevelopmental Mechanisms

“…Affecting as many as 1 in 2700 newborns [61], neurofibromatosis type 1 (NF1) is a monogenic disorder characterized by both physical and cognitive symptoms. Hallmarks of the syndrome include café-au-lait spots and benign nerve tumors known as neurofibromas.…”

Worries and needs of adults and parents of adults with neurofibromatosis type 1

“…Neurofibromatosis type 1 (NF1) is a relatively common autosomal dominant neurocutaneous disorder with an estimated birth incidence of 1/2,700 (Evans et al, 2010). Approximately 40% to 50% of the cases are caused by a de novo mutation in the NF1 gene (Evans et al, 2010; Friedman, 1999).…”

“…Approximately 40% to 50% of the cases are caused by a de novo mutation in the NF1 gene (Evans et al, 2010; Friedman, 1999). Clinical features of NF1 include multiple café‐au‐lait spots, axillary and inguinal freckling, multiple cutaneous neurofibromas, and iris Lisch nodules (NIH, 1987).…”

Multiple tumor types including leiomyoma and Wilms tumor in a patient with Gorlin syndrome due to 9q22.3 microdeletion encompassing the PTCH1 and FANC‐C loci

“…Exonic, multiexonic, and whole-gene deletions have been reported in about 6% of individuals with NBCCS [Evans and Farndon, 2002]. The studies of disease prevalence come from the UK population, where it is nearer to 1:30,827 [Evans et al, 2010]; The actual figure could be higher still, since less severe cases may not be diagnosed and Jones et al [2011] recently reported an incidence of 1 in 19,000 births.…”

“…Exonic, multiexonic, and whole-gene deletions have been reported in about 6% of individuals with NBCCS [Evans and Farndon, 2002]. The studies of disease prevalence come from the UK population, where it is nearer to 1:30,827 [Evans et al, 2010]; The actual figure could be higher still, since less severe cases may not be diagnosed and Jones et al [2011] recently reported an incidence of 1 in 19,000 births.NBCCS is clinically diagnosed in patients with one major diagnostic criterion and molecular confirmation or two major criteria or one major and two minor diagnostic criteria [Bree et al, 2011]. The major criteria are the following: (1) BCC before the age of 20 or excessive numbers of BBCs out of proportion to prior sun exposure and skin type, (2) odontogenic jaw keratocyst prior to 20 years of age, (3) palmar or plantar pitting, (4) lamellar calcification of the falx cerebri, (5) medulloblastoma typically desmoplastic, and (6) first-degree relative with NBCCS.…”