This Tumours of postganglionic sympathetic neurons is the most common solid Tumours in children. Most cases are sporadic; familial cases (in which predisposition to neuroblastoma is inherited as an autosomal dominant trait) account for less than 1 % of the total. However, in a statistical analysis of the age at onset of neuroblastoma, Knudson and Strong (1972) estimated that 22% of neuroblastomas could result from a germinal mutation and follow a “single-hit” mutation model, as in inherited retinoblastoma (Knudson 1971). The mean age at diagnosis of familial cases is 9 months (60 % at less than 1 year) compared to 30 months (25 % at less than 1 year) in nonfamilial cases (Kushner et al. 1986), and familial Tumours are frequently multiple (Robertson et al. 1991).
Neuroblastoma is occasionally seen in overgrowth disorders such as Beckwith–Wiedemann syndrome and hemihypertrophy and in disorders associated with abnormal neural crest differentiation such as NF1, Hirschsprung disease, and congenital central hypoventilation syndrome. Germline mutations in PHOX2B were initially demonstrated in congenital central hypoventilation syndrome and subsequently in patients with neuroblastoma in association with congenital central hypoventilation syndrome and/or Hirschsprung disease and in familial non-syndromic neuroblastoma (Trochet et al. 2004). Although germline PHOX2B mutations may occasionally be found in patients with apparently sporadic neuroblastoma, overall it appears to be a rare cause of inherited neuroblastoma (Perri et al. 2005; McConville et al. 2006; Raabe et al. 2008).
Frequent somatic changes in neuroblastoma include MYCN amplification, chromosome 1p36 and 11q allele loss, and copy number gain at 17q. In addition, copy number gain and activating mutations in the anaplastic lymphoma kinase (ALK1) proto-oncogene were found to be a common event (Chen et al. 2008; Janoueix-Lerosey et al. 2008; Mossé et al. 2008).
Furthermore, germline ALK1 mutations are an important cause of familial neuroblastoma (Janoueix-Lerosey et al. 2008; Mossé et al. 2008).
Neuroblastoma susceptibility associated with ALK1 missense mutations is inherited as an autosomal dominant trait with incomplete penetrance and often manifests with multiple Tumours (Bourdeaut et al. 2012). Two de novo ALK1 mutations have been associated with a novel syndrome of multifocal congenital neuroblastoma, encephalopathy, and abnormal brainstem morphology (de Pontual et al. 2011).
Genome-wide association studies have linked aggressive neuroblastoma susceptibility to common genomic variants at chromosome 6p22 and SNPs in BARD1 (which interacts with BRCA1) (Maris et al. 2008; Capasso et al. 2009).
In familial neuroblastoma, screening by urinary catecholamine estimations from birth to age 6 years can be offered. However, although initially advocated, population screening of infants for neuroblastoma was not found to reduce mortality (Woods et al. 2002).