ALK or PHOX2B – risk management

Familial neuroblastoma predisposition is an autosomal dominant cancer predisposition due to a heritable pathogenic variant in the ALK gene or the PHOX2B gene.

This risk management guideline has been developed for individuals who have NOT been diagnosed with a relevant cancer/tumour. The care of affected individuals should be individualised based on their clinical situation, and the monitoring they need as part of their treatment and post-treatment follow up.

The risk management of an individual with a pathogenic variant in two or more genes that confer a predisposition to cancer should also be individualised.

Unaffected individual <18 years of age with or obligate carrier of:

• an ALK pathogenic variant
• a pathogenic PHOX2B non-polyalanine repeat mutation (NPARM)

Exclusion criteria

• Individual >18 years of age
• Individual who tested negative for a familial ALK or a PHOX2B pathogenic variant

* NPARM: non-polyalanine repeat mutation; PARM: polyalanine repeat mutation

There is currently no international consensus on screening. Surveillance protocols have been proposed by expert groups but have not been systematically studied.

* The impact of lifestyle on cancer risk should be discussed e.g. exercise regularly, maintain a healthy weight, have a healthy diet, limit alcohol intake, do not smoke and avoid excessive sun exposure.

** VMA: vanillylmandelic acid; HVA: homovanillic acid

Surveillance

There are limited data on the effectiveness of cancer screening in ALK or PHOX2B pathogenic variant carriers. Published recommendations represent expert opinion and are extrapolated from cancer screening studies in the general population. 

Population screening for neuroblastoma (NB) by measuring urinary catecholamine metabolites in newborn, infancy and at 1 year of age was shown to be effective for screening for presymptomatic NB but resulted in a significantly increased incidence of NB, no decrease in NB in children over 1 year of age and no difference in mortality.^r,r However, experts suggest that screening using a combination of abdominal ultrasound, urine catecholamines and chest X-rays may be useful in a targeted population of children at increased risk of NB due to a hereditary predisposition.^r

First degree blood relatives (parents/brothers/sisters/children) are at 50% risk of having inherited a gene pathogenic variant or having the condition. First degree relatives should be referred to a clinical genetics service or familial cancer centre.

Informing family members about hereditary cancer

Centre for Genetics Education NSW Health
Genetic Alliance Australia

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