Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Response to the article by Linnankivi et al., entitled ‘Cerebroretinal microangiopathy with calcifications and cyst, Revesz syndrome and aplastic anemia’

Bone Marrow Transplantation volume 48, page 154 (2013)Cite this article

Subjects

We appreciate the interest and comments by Dr Linnankivi regarding our article entitled ‘‘Allo-SCT in a patient with CRMCC with aplastic anemia using a reduced intensity conditioning regimen’’.1 The relationship between Revesz syndrome and cerebroretinal microangiopathy with calcifications and cysts (CRMCC) was not clear until the CTC1 (encoding conserved telomere maintenance component 1) mutation was identified.2, 3 The definition of CRMCC originally encompassed Coats plus syndrome, Labrune syndrome and leukoencephalopathy, the brain calcifications and cysts of which are associated with characteristic central nervous system abnormalities, such as extensive intracranial calcification and leukoencephalopathy.4 Coats plus syndrome is also characterized by the presence of bilateral exudative retinopathy.4 In addition, some Coats plus patients show evidence of nail dystrophy, sparse hair and anemia, which are similar to the symptoms of dyskeratosis congenita (DKC).5 On the other hand, Revesz syndrome was originally described in a male infant with bilateral exudative retinopathy, intracranial calcifications, cysts in the brain, leukoencephalopathy and aplastic anemia.6 These findings suggested that Revesz syndrome might be a severe variant of Coats plus syndrome. Therefore, we experienced difficulty in clinically distinguishing Revesz syndrome from CRMCC/Coats plus syndrome based on the severity of the hematological complications. Recently, a TINF2 mutation was identified in patients with DKC and Revesz syndrome, suggesting that Revesz syndrome is, in fact, a variant of DKC.7, 8 Subsequently, Anderson et al.2 and Polvi et al.3 identified mutations in the CTC1 gene that were responsible for Coats plus syndrome in some patients. Therefore, we diagnosed our patient with Coats plus syndrome based on these genetic abnormalities, leading to further understanding of the phenotypic details/differences caused by these genetic alterations. However, we now agree that our patient has Revesz syndrome harboring the TINF2 mutation,7, 8 which is distinct from CRMCC/Coats plus syndrome harboring mutations in CTC1.2, 3 Further genetic analyses are needed to examine whether the CTC1 mutation causes severe aplastic anemia, especially in DKC patients with unidentified genetic alterations, because TINF2 mutations have been identified in DKC patients without any symptoms of Revesz syndrome.8 Therefore, it is mandatory that allogeneic hematopoietic SCT with a reduced intensity conditioning regimen should be considered for all patients with severe aplastic anemia harboring genetic alterations that cause telomere dysfunction.9

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Linnankivi T, Polvi A, Mäkitie O, Lehesjoki A-E, Kivelä T . Cerebroretinal microangiopathy with calcifications and cysts, Revesz syndrome and aplastic anemia. Bone Marrow Transplant 2012 (this issue).

  2. Anderson BH, Kasher PR, Mayer J, Szynkiewicz M, Jenkinson EM, Bhaskar SS et al. Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus. Nat Genet 2012; 44: 338–342.

    Article  CAS  Google Scholar 

  3. Polvi A, Linnankivi T, Kivelä T, Herva R, Keating JP, Mäkitie O et al. Mutations in CTC1, encoding the CTS Telomere Maintenance Complex Component 1, cause cerebroretinal microangiopathy with calcifications and cysts. Am J Hum Genet 2012; 90: 540–549.

    Article  CAS  Google Scholar 

  4. Briggs TA, Abdel-Salam GM, Balicki M, Baxter P, Bertini E, Bishop N et al. Cerebroretinal microangiopathy with calcifications and cysts (CRMCC). Am J Med Genet A 2008; 146A: 182–190.

    Article  CAS  Google Scholar 

  5. Savage SA . Connecting complex disorders through biology. Nat Genet 2012; 44: 238–240.

    Article  CAS  Google Scholar 

  6. Revesz T, Fletcher S, al-Gazali LI, DeBuse P . Bilateral retinopathy, aplastic anemia, and central nervous system abnormalities: a new syndrome? J Med Genet 1992; 29: 673–675.

    Article  CAS  Google Scholar 

  7. Savage SA, Giri N, Baerlocher GM, Orr N, Lansdorp PM, Alter BP . TINF2, a component of sheltrin telomere protection complex, is mutated in dyskeratosis congenital. Am J Hum Genet 2008; 82: 501–509.

    Article  CAS  Google Scholar 

  8. Walne AJ, Vulliamy T, Beswick R, Kirwan M, Dokal I . TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes. Blood 2008; 112: 3594–3600.

    Article  CAS  Google Scholar 

  9. Dietz AC, Orchard PJ, Baker KS, Giller RH, Savage SA, Alter BP et al. Disease-specific hematopoietic cell transplantation: nonmyeloablative conditioning regimen for dyskeratosis congenita. Bone Marrow Transplant 2011; 46: 98–104.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan

    D Asai, T Imamura & H Hosoi

  2. Division of Pediatrics, Kyoto City Hospital, Kyoto, Japan

    S Osone & H Kuroda

  3. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan

    H Sakaguchi, N Nishio & S Kojima

Authors
  1. D Asai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S Osone
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T Imamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H Sakaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N Nishio
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H Kuroda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S Kojima
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H Hosoi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T Imamura.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Asai, D., Osone, S., Imamura, T. et al. Response to the article by Linnankivi et al., entitled ‘Cerebroretinal microangiopathy with calcifications and cyst, Revesz syndrome and aplastic anemia’. Bone Marrow Transplant 48, 154 (2013). https://doi.org/10.1038/bmt.2012.108

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2012.108

Search

Advanced search

Quick links