Hereditary Renal Cancer Syndromes
Round 1
Reviewer 1 Report
Comments and Suggestions for Authors
I read the manuscript titled "Hereditary kidney cancer" with interest. I suggest the following title "Hereditary Renal Cancer Syndromes".
I suggest you use MeSH terms for keywords.
In general, although this is not the first narrative review on this topic, I think you have put in the effort.
Please, at the end of the introduction, briefly state the purpose of the review. I also ask that the tables and figures appear within the text in the order you list them.
I suggest that you form section 2 under the title diseases/syndromes or similar according to your opinion and that you form all diseases/syndromes as subsections (2.1., 2.2., etc...).
Are you the authors of figure 1?
It is not usual to list a table within the conclusion.
More than 50% of the references are from the last 8 years, which is commendable.
Comments on the Quality of English Language
Moderate editing of English language required.
Author Response
Comment: I suggest you use MeSH terms for keywords.
Response: We have changed the keywords.
Comment: Please, at the end of the introduction, briefly state the purpose of the review. I also ask that the tables and figures appear within the text in the order you list them.
Response: We have inserted the following statement: “This review provides an update on clinical and genetic aspects of inherited predisposition to kidney cancer”.
Comment: I suggest that you form section 2 under the title diseases/syndromes or similar according to your opinion and that you form all diseases/syndromes as subsections (2.1., 2.2., etc...).
Response: This is done.
Comment: Are you the authors of figure 1?
Response: Yes
Comment: It is not usual to list a table within the conclusion.
Response: We have moved this table close to the first mention on the treatment of hereditary cancer syndromes.
Reviewer 2 Report
Comments and Suggestions for Authors
The authors present a nicely written review of the various hereditary kidney cancers. The review is comprehensive, up to date, and contains useful tables.
A few areas of improvement
1. the surveillance recommendations of these different syndromes should be listed somewhere (e.g. what imaging modality, how often, and at what age to start). Table 3 is an option
2. The controversy around FH c.1431_1433dupAAA (p.Lys477dup) should be mentioned with respect to HLRCC and FH deficiency
3. the pathway figure 1 could be improved in terms of being more professional looking. This could be done in collaboration with a medical graphic artist.
Comments on the Quality of English Language
no comments, english is adequate
Author Response
Comment: The surveillance recommendations of these different syndromes should be listed somewhere (e.g. what imaging modality, how often, and at what age to start). Table 3 is an option
Response: We have inserted a new table describing the surveillance recommendations.
Comment: The controversy around FH c.1431_1433dupAAA (p.Lys477dup) should be mentioned with respect to HLRCC and FH deficiency
Response: We have inserted comments on this issue:
“While heterozygous inactivation of FH is associated with FHTPS/HLRCC, individuals with biallelic germline FH deficiency (constitutional fumarase deficiency) demonstrate a mitochondrial encephalopathy phenotype but no increased cancer risk. Rare hypomorphic FH variants are described, which are associated with FH deficiency while being in a biallelic state, but not with HLRCC when present in heterozygotes. The most studied example is the FH c.1431_1433dupAAA (p.Lys477dup) allele [129]. It causes constitutional FH deficiency when present in trans with another loss-of-function FH mutation, but its heterozygous carriers are not affected by FHTPS/HLRCC.”
Comment: The pathway figure 1 could be improved in terms of being more professional looking. This could be done in collaboration with a medical graphic artist.
Response: We have revised this figure.
