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Case Reports
. 2018 Sep 12;19(1):164.
doi: 10.1186/s12881-018-0682-x.

Three cases of multicentric carpotarsal osteolysis syndrome: a case series

Affiliations
Case Reports

Three cases of multicentric carpotarsal osteolysis syndrome: a case series

Peong Gang Park et al. BMC Med Genet. .

Abstract

Background: Multicentric carpotarsal osteolysis syndrome (MCTO) is characterized by progressive destruction and disappearance of the carpal and tarsal bones associated with nephropathy. MCTO is caused by loss-of-function mutations in the MAF bZIP transcription factor B (MAFB) gene.

Case presentation: This report describes three unrelated patients with MAFB mutations, including two male and one female patient. Osteolytic lesions in the carpal and tarsal bones were detected at 2 years, 12 years, and 14 months of age, respectively. Associated proteinuria was noted at 4 years, 12 years, and 3 months of age, respectively. Kidney biopsy was performed in two of them and revealed focal segmental glomerulosclerosis (FSGS). One patient showed progression to end-stage renal disease, that is by 1 year after the detection of proteinuria. The second patient had persistent proteinuria but maintained normal renal function. In the third patient, who did not undergo a kidney biopsy, the proteinuria disappeared spontaneously. The bony lesions worsened progressively in all three patients. Mutational study of MAFB revealed three different mutations, two novel mutations [c.183C > A (p.Ser61Arg) and c.211C > G (p.Pro71Ala)] and one known mutation [c.212C > T (p.Pro71Leu)].

Conclusion: We report three cases with MCTO and two novel MAFB mutations. The renal phenotypes were different among the three patients, whereas progressive worsening of the bony lesions was common in all patients. We also confirmed FSGS to be an early renal pathologic finding in two cases. A diagnosis of MCTO should be considered in patients with progressive bone loss concentrated primarily in the carpal and tarsal bones and kidney involvement, such as proteinuria.

Keywords: Focal segmental glomerular sclerosis; Idiopathic osteolysis; MAFB gene; Multicentric carpotarsal osteolysis syndrome; Proteinuria.

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Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Seoul National University Hospital’s Institutional Review Board (IRB No. 0812–002-264). The patients and their parents provided informed consent to participate in this study.

Consent for publication

The parents of the patients provided informed consent to publish this case report, including case description, medical data, and images.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Radiological findings of 2 patients with multicentric carpotarsal osteolysis syndrome. In Patient 1, radiographs of the hands (a) and feet (b) obtained at 4 years old show severe bone resorption of the carpal and tarsal bones. Bone erosions are also noted in the proximal ends of metacarpal and metatarsal bones and the distal ends of the talus and calcaneus. Note that the distal metacarpal and metatarsal bones and the phalanges remained well-preserved at that time. Incidentally, there are fractures of the left 2nd and 3rd metatarsal necks (arrows). Follow-up radiographs of the hands (c) and feet (d) at the age of 20 show marked progression of bone resorption and associated joint contracture. In addition to the carpal and tarsal bones, the metacarpal and metatarsal bones, phalanges, distal radii, and ulnae are extensively involved. In Patient 3, radiographs of the hands (e) and feet (not shown) obtained at 1 year of age show multiple areas of osteolysis predominantly involving the carpal and tarsal bones. In addition, an abdominal aortic aneurysm was incidentally detected with renal ultrasonography (not shown), and a subsequently taken abdominal CT angiograph (f) confirmed fusiform aneurysms involving the infrarenal aorta and bilateral common iliac arteries (arrows)
Fig. 2
Fig. 2
Renal pathological findings of 2 patients with multicentric carpotarsal osteolysis syndrome. In Patient 1, light microscopy (a) shows a glomerulus with segmental sclerosis (arrow), tubular atrophy, and interstitial fibrosis (hematoxylin and eosin, × 200). Electron microscopy (b) reveals wide effacement of foot process (arrow). (scale bar = 10 μm) In Patient 2, light microscopy shows a glomerulus perihilar segmental sclerosis (c, periodic acid–Schiff, × 400) and mild to moderate tubulointerstitial fibrosis with tubular atrophy (d, Masson’s trichrome, × 200), and electron microscopy (e) reveals wide effacement of the foot processes with occasional villous transformation and hydropic change of podocytes. (scale bar = 10 μm)
Fig. 3
Fig. 3
Pedigrees and sequence chromatograms of the patients and their parents. Patients 1 and 3 carry a de novo heterozygous mutation of c.211C > G (p.Pro71Ala) and c.212C > T (p.Pro71Leu) in the MAFB gene, respectively. Patient 2 carries a heterozygous MAFB mutation, c.183C > A (p.Ser61Arg). Her mother does not carry the mutation and her father’s sample was unavailable

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