NEUROBLASTOMA, SUSCEPTIBILITY TONEUROBLASTOMA, SUSCEPTIBILITY TO, 1, INCLUDED

General Information (adopted from Orphanet):

Synonyms, Signs: NBLST1, INCLUDED
Number of Symptoms 28
OrphanetNr:
OMIM Id: 256700
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal dominant inheritance
Heterogeneous
Sporadic
[Omim]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: No data available.

Symptom Information: Sort by abundance 

1
(HPO:0010543) Opsoclonus 2 / 7739
2
(HPO:0002277) Horner syndrome 7 / 7739
3
(HPO:0001336) Myoclonus 115 / 7739
4
(HPO:0001251) Ataxia 413 / 7739
5
(HPO:0003005) Ganglioneuroma 6 / 7739
6
(HPO:0006747) Ganglioneuroblastoma 5 / 7739
7
(HPO:0002653) Bone pain 75 / 7739
8
(HPO:0002028) Chronic diarrhea 51 / 7739
9
(HPO:0002027) Abdominal pain 184 / 7739
10
(HPO:0002014) Diarrhea 225 / 7739
11
(HPO:0001824) Weight loss 42 / 7739
12
(HPO:0001508) Failure to thrive 454 / 7739
13
(HPO:0000822) Hypertension 224 / 7739
14
(HPO:0001903) Anemia 289 / 7739
15
(HPO:0011978) Elevated urinary vanillylmandelic acid 2 / 7739
16
(HPO:0011977) Elevated urinary homovanillic acid 2 / 7739
17
(OMIM) Mediastinal mass with calcifications on radiology 1 / 7739
18
(OMIM) Bluish skin nodules 1 / 7739
19
(HPO:0002176) Spinal cord compression 15 / 7739
20
(OMIM) Abdominal mass with calcifications on radiology 1 / 7739
21
(OMIM) Adrenal glands are most common site 1 / 7739
22
(OMIM) Increased urinary dopamine 1 / 7739
23
(MedDRA:10059420) Paraneoplastic syndrome 1 / 7739
24
(OMIM) Neuroblastoma, arises anywhere along the sympathetic chain (including intracranially) 1 / 7739
25
(OMIM) Periorbital ecchymoses (soft tissue involvement) 1 / 7739
26
(OMIM) Palpable abdominal mass 1 / 7739
27
(OMIM) Increased urinary catecholamines 2 / 7739
28
(OMIM) Tumor may secrete vasoactive intestinal peptide (VIP) 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Neuroblastoma is the most common childhood cancer diagnosed before the age of 1 year, and accounts for 10 to 15% of all cancer deaths in children. Some patients inherit a genetic predisposition to neuroblastoma due to germline mutations, ...
Clinical Description OMIM - Early Familial Reports

Dodge and Benner (1945) reported a brother and sister with neuroblastoma of the adrenal medulla. In the family of Zimmerman (1951), the father had had a mediastinal ganglioneuroma removed at age 10 ...

Molecular genetics OMIM - Germline Mutations in the KIF1B Gene

In 1 pheochromocytoma (171300) and 3 neuroblastoma tumor samples and in corresponding germline DNA samples from the respective patients, Schlisio et al. (2008) identified 4 different missense mutations in ...

Diagnosis GeneReviews Individuals with ALK-related neuroblastoma susceptibility (i.e., heterozygous for an ALK mutation) are at risk of developing neuroblastoma, ganglioneuroblastoma, or ganglioneuroma. Often the family history is positive for one or more relatives with one of these tumors [Mossé et al 2008] with both benign and malignant forms occurring in the same family. ...
Clinical Description GeneReviews Individuals with ALK-related neuroblastoma susceptibility (i.e., heterozygous for ALK mutations) are at risk of developing neuroblastoma, ganglioneuroblastoma, or ganglioneuroma. The risk for tumor development is highest in infancy and decreases by late childhood. Individuals with familial neuroblastoma tend to develop tumors at a younger age (average 9 months) than those without familial predisposition (age 2-3 years) [Park et al 2008]. Individuals with familial neuroblastoma also have a higher incidence of multiple primary tumors [Mossé et al 2008, Park et al 2008]. There are no data at present regarding the specific percentage of individuals with germline mutations in ALK who will develop tumors in their lifetime. ...
Genotype-Phenotype Correlations GeneReviews The vast majority (91%) of ALK disease-causing mutations fall within the kinase domain [Chen et al 2008]. All reported mutations in the kinase domain appear to be oncogenic [Mossé et al 2008].The most commonly reported germline mutation is p.Arg1275Gln, found in approximately 45% of cases [Wood et al 2009]; it is also the most common somatic mutation. This mutation may be associated with somewhat decreased penetrance (40%) compared with all other reported mutations (61%) [Eng 2008]. ...
Differential Diagnosis GeneReviews Germline mutations in ALK and PHOX2B are the etiologic agents for familial neuroblastoma susceptibility. Germline mutations in ALK are the main cause of familial susceptibility to neuroblastoma in otherwise healthy families. Heterozygous germline mutations in PHOX2B account for the remainder of families, most of whom also have disorders of neural crest development (see PHOX2B) [Mossé et al 2008, Azarova et al 2011]. ...
Management GeneReviews No guidelines have been established for initial screening for individuals diagnosed with ALK-related neuroblastoma susceptibility. ...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....