Thiemann disease and familial digital arthropathy – brachydactyly: two sides of the same coin?

Orphanet Journal of Rare Diseases

  ^{1    2    3    4    5    6    6    7} 

[1] 0000 0001 2157 2938, grid.17063.33, Division of Rheumatology, Department of Paediatrics and Medicine, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada;0000 0001 2161 2573, grid.4464.2, Department of Rheumatology The Royal London Hospital, The University of London, E1 4DG, London, UK;0000 0001 2179 088X, grid.1008.9, Victorian Clinical Genetics Service, Murdoch Childrens Research Institute, The University of Melbourne, Melbourne, Australia;0000 0004 0473 9646, grid.42327.30, Department of Diagnostic Imaging, The Hospital for Sick Children University of Toronto, Toronto, ON, Canada;0000 0004 0473 9646, grid.42327.30, Department of Paediatric Laboratory Medicine and Laboratory Medicine and Pathobiology, The Hospital for Sick Children and University of Toronto, M5G 1X8, Toronto, ON, Canada;0000 0004 0473 9646, grid.42327.30, Division of Clinical and Metabolic Genetics, The Hospital for Sick Children and University of Toronto, M5G 1X8, Toronto, ON, Canada;0000 0004 0473 9646, grid.42327.30, Division of Clinical and Metabolic Genetics, The Hospital for Sick Children and University of Toronto, M5G 1X8, Toronto, ON, Canada;0000 0004 0473 9646, grid.42327.30, Developmental and Stem Cell Biology, The Hospital for Sick Children, M5G 1X8, Toronto, ON, Canada;

关键词: TRPV4;    Hand;    Osteonecrosis;    Osteoarthritis;    Arthritis;   

DOI  :  10.1186/s13023-019-1138-x

来源: publisher

【 摘 要 】

BackgroundFamilial digital arthropathy-brachydactyly (FDAB) and Thiemann disease are non-inflammatory digital arthropathies with many phenotypic similarities. Thirty-three cases of Thiemann disease have been described so far (Mangat et al, Ann Rheum Dis 64:11-2, 2005; Ha et al, Thiemann's disease: a case Report, 2017) but no gene variants have been identified as causative to date. FDAB is reported in only a few patients and has been associated with three heterozygous missense variants in the Transient receptor potential vanilloid 4 (TRPV4) gene. We report a TRPV4 variant in a father and son referred with a diagnosis of Thiemann disease and compare the clinical and radiological features of Thiemann disease with Familial digital arthropathy-brachydactyly (FDAB). We hypothesize that these two entities may be one and the same.MethodsWe describe a father and son referred with a diagnosis of Thiemann disease who were subsequently identified with a heterozygous variant (c.809G > T) in TRPV4. The identical genetic variant was previously reported to cause FDAB. A PUBMED® database search was conducted to retrieve articles related to Thiemann disease and FDAB. We were able to review the clinical and radiological findings of nineteen individuals affected by Thiemann disease and compare them with three families affected by FDAB.ResultsThiemann disease initially affects the proximal interphalangeal joints and primarily the middle phalangeal bases. In FDAB, the distal phalangeal joints are first affected with the middle phalangeal heads being the primary site of changes. Radial deviation has only been described in FDAB. Our analysis determined that 5 of 20 individuals affected by Thiemann disease have clinical and radiological findings that also fit well with FDAB.ConclusionFDAB and Thiemann disease are non-inflammatory digital arthropathies with phenotypic overlap. Although more extensive joint involvement, a distal hand joint preponderance and brachydactyly are expected in FDAB, there are striking clinical and radiological similarities between the two entities. Our analysis suggests that these two phenotypes may represent phenotypic variability of the same entity. Despite many attempts to identify other reported patients affected by Thiemann disease, we were not able to procure DNA from any of the cases to verify our findings. Genetic testing of an affected individual will be crucial in order to provide accurate reproductive genetic counselling about the autosomal dominant nature of this condition.

【 授权许可】

CC BY