An ALK-related predisposition to neuroblastic tumors (OMIM #613014) is due to a heterozygous germline mutation of the anaplastic lymphoma kinase (ALK) gene and predisposes to the development of neuroblastomas, ganglioneuroblastomas, and ganglioneuromas, specifically during infancy and childhood. It is also possible for tumors to develop in the adrenal glands and in the region of the sympathetic ganglia.
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|Synonym||Predispostion to neuroblastoma|
|Gene||ALK (anaplastic lymphoma kinase)|
|Gene product||ALK tyrosine kinase receptor|
|Function||Membrane tyrosine kinase, which controls the proliferation of immature sympathetic neurons|
|Prevalence||Approximately 1-2% of neuroblastoma patients|
|Genotype-phenotype correlation||With the exception of the following three pathogenic variants, there are no known associations between specific ALK mutations and the risk of developing neuroblastoma or the outcome of neuroblastoma.
|Penetrance||Incomplete; presumed to be approximately 50%|
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Clinical Diagnostic Criteria
The following findings constitute a potential ALK-related predisposition to neuroblastic tumors:
The diagnosis “ALK-related predisposition to neuroblastic tumors” is confirmed by the detection of a heterozygous germline ALK mutation that alters the amino acid sequence of the tyrosine kinase domain.
Patients with an ALK-related predisposition to neuroblastic tumors are at increased risk of developing the following neuroblastic tumors:
The risk of developing neuroblastic tumors is highest during infancy and decreases with increasing age. Tumors occur earlier (on average at 9 months of age) in cases of familial neuroblastoma compared with cases without a familial neuroblastoma predisposition (on average at 2-3 years of age).
In addition, there is a greater risk of developing multiple primary tumors in the case of familial neuroblastoma compared to the non-familial form. These multiple primary tumors may be bilateral adrenal gland tumors or tumors external to the adrenal glands that form in the region of sympathetic ganglia. Tumors may occur synchronously or metachronously.
The outcome of neuroblastic tumors is largely dependent on tumor type, tumor stage, and the effectiveness of therapy and less dependent on the presence of an ALK germline mutation.
Treatment is in accordance with the treatment guidelines of the neuroblastoma study. An ALK inhibitor therapy option should be discussed with the study.
There are no standard recommendations to date. The following is a potential approach for the early detection of neuroblastic tumors in cases where an ALK mutation has been detected:
Clinical examination, ultrasound of the abdomen, measurement of catecholamines, urin VMA, and HVA, X-ray of the thorax (PA and lateral):
Following the successful treatment of a neuroblastic tumor, the early detection examinations should be continued up to 10 years of age to minimize the risk of developing multiple primary tumors.
Open Clinical Trials / Registries
Unfortunately, we are as yet unaware of any existing self-help groups for patients with an ALK-related predisposition to neuroblastic tumors. We will add any new information in this regard as soon as we learn of it.