Familial tumoral calcinosis

A forty-year follow-up on one family

Kelly Carmichael, James A. Bynum, E. Burke Evans

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background: Familial tumoral calcinosis is a rare autosomal recessive disorder that was first described well in a report on four patients from one family in 1969. The disease leads to periarticular ectopic calcifications. The original report described patients from black, healthy, unrelated parents with sixteen children, seven of whom had the disease. Methods: On the basis of retrospective chart reviews and interviews with surviving family members, we describe the long- term follow-up of this one family, encompassing as long as forty years. Of the sixteen siblings, seven had tumoral calcinosis. Results: All seven affected children had hyperphosphatemia. There were two subsequent generations comprising thirteen children and seven grandchildren with no instances of tumoral calcinosis. The seven affected patients were followed for as many as forty years and underwent an average of twenty-one operations (range, four to thirty-six operations) for the treatment of calcified lesions. The genetic defect has been identified as the GALNT3 gene, thus leading to the hyperphosphatemic form of the disease. Although two of the patients had died by the time of the present study, the remaining five provided accounts of the disease course, the response to surgery and to medical therapy, and the effect of therapy on their lives. Some members had relatively few lesions and surgical procedures (as few as four), whereas others had an unrelenting course of lesions, recurrences, and surgical procedures (as many as thirty-six, with numerous other procedures). Three patients had multiyear periods with few symptoms-one for seven years, one for twelve years, and one for fifteen years. No effective medical therapy was found to control the lesions, and operations were associated with a high recurrence rate. Conclusions: Familial tumoral calcinosis has a varied natural history; some patients have an unrelenting course, while others may experience quiescent periods. The GALNT3 gene is responsible for the hyperphosphatemic form as seen in this family. Molecular testing may be of benefit to members of affected families, and future studies may help to explain the phenotypic variability among affected individuals. No medical or surgical treatment plan seemed to be effective for controlling the lesions in this family.

Original languageEnglish (US)
Pages (from-to)664-671
Number of pages8
JournalJournal of Bone and Joint Surgery - Series A
Volume91
Issue number3
DOIs
StatePublished - Mar 1 2009

Fingerprint

Calcinosis
Hyperphosphatemia
Therapeutics
Recurrence
Natural History
Genes
Siblings
Parents
Interviews

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

Cite this

Familial tumoral calcinosis : A forty-year follow-up on one family. / Carmichael, Kelly; Bynum, James A.; Evans, E. Burke.

In: Journal of Bone and Joint Surgery - Series A, Vol. 91, No. 3, 01.03.2009, p. 664-671.

Research output: Contribution to journalArticle

@article{61c1c657685c468b980271eb0d99090b,
title = "Familial tumoral calcinosis: A forty-year follow-up on one family",
abstract = "Background: Familial tumoral calcinosis is a rare autosomal recessive disorder that was first described well in a report on four patients from one family in 1969. The disease leads to periarticular ectopic calcifications. The original report described patients from black, healthy, unrelated parents with sixteen children, seven of whom had the disease. Methods: On the basis of retrospective chart reviews and interviews with surviving family members, we describe the long- term follow-up of this one family, encompassing as long as forty years. Of the sixteen siblings, seven had tumoral calcinosis. Results: All seven affected children had hyperphosphatemia. There were two subsequent generations comprising thirteen children and seven grandchildren with no instances of tumoral calcinosis. The seven affected patients were followed for as many as forty years and underwent an average of twenty-one operations (range, four to thirty-six operations) for the treatment of calcified lesions. The genetic defect has been identified as the GALNT3 gene, thus leading to the hyperphosphatemic form of the disease. Although two of the patients had died by the time of the present study, the remaining five provided accounts of the disease course, the response to surgery and to medical therapy, and the effect of therapy on their lives. Some members had relatively few lesions and surgical procedures (as few as four), whereas others had an unrelenting course of lesions, recurrences, and surgical procedures (as many as thirty-six, with numerous other procedures). Three patients had multiyear periods with few symptoms-one for seven years, one for twelve years, and one for fifteen years. No effective medical therapy was found to control the lesions, and operations were associated with a high recurrence rate. Conclusions: Familial tumoral calcinosis has a varied natural history; some patients have an unrelenting course, while others may experience quiescent periods. The GALNT3 gene is responsible for the hyperphosphatemic form as seen in this family. Molecular testing may be of benefit to members of affected families, and future studies may help to explain the phenotypic variability among affected individuals. No medical or surgical treatment plan seemed to be effective for controlling the lesions in this family.",
author = "Kelly Carmichael and Bynum, {James A.} and Evans, {E. Burke}",
year = "2009",
month = "3",
day = "1",
doi = "10.2106/JBJS.G.01512",
language = "English (US)",
volume = "91",
pages = "664--671",
journal = "Journal of Bone and Joint Surgery - American Volume",
issn = "0021-9355",
publisher = "Journal of Bone and Joint Surgery Inc.",
number = "3",

}

TY - JOUR

T1 - Familial tumoral calcinosis

T2 - A forty-year follow-up on one family

AU - Carmichael, Kelly

AU - Bynum, James A.

AU - Evans, E. Burke

PY - 2009/3/1

Y1 - 2009/3/1

N2 - Background: Familial tumoral calcinosis is a rare autosomal recessive disorder that was first described well in a report on four patients from one family in 1969. The disease leads to periarticular ectopic calcifications. The original report described patients from black, healthy, unrelated parents with sixteen children, seven of whom had the disease. Methods: On the basis of retrospective chart reviews and interviews with surviving family members, we describe the long- term follow-up of this one family, encompassing as long as forty years. Of the sixteen siblings, seven had tumoral calcinosis. Results: All seven affected children had hyperphosphatemia. There were two subsequent generations comprising thirteen children and seven grandchildren with no instances of tumoral calcinosis. The seven affected patients were followed for as many as forty years and underwent an average of twenty-one operations (range, four to thirty-six operations) for the treatment of calcified lesions. The genetic defect has been identified as the GALNT3 gene, thus leading to the hyperphosphatemic form of the disease. Although two of the patients had died by the time of the present study, the remaining five provided accounts of the disease course, the response to surgery and to medical therapy, and the effect of therapy on their lives. Some members had relatively few lesions and surgical procedures (as few as four), whereas others had an unrelenting course of lesions, recurrences, and surgical procedures (as many as thirty-six, with numerous other procedures). Three patients had multiyear periods with few symptoms-one for seven years, one for twelve years, and one for fifteen years. No effective medical therapy was found to control the lesions, and operations were associated with a high recurrence rate. Conclusions: Familial tumoral calcinosis has a varied natural history; some patients have an unrelenting course, while others may experience quiescent periods. The GALNT3 gene is responsible for the hyperphosphatemic form as seen in this family. Molecular testing may be of benefit to members of affected families, and future studies may help to explain the phenotypic variability among affected individuals. No medical or surgical treatment plan seemed to be effective for controlling the lesions in this family.

AB - Background: Familial tumoral calcinosis is a rare autosomal recessive disorder that was first described well in a report on four patients from one family in 1969. The disease leads to periarticular ectopic calcifications. The original report described patients from black, healthy, unrelated parents with sixteen children, seven of whom had the disease. Methods: On the basis of retrospective chart reviews and interviews with surviving family members, we describe the long- term follow-up of this one family, encompassing as long as forty years. Of the sixteen siblings, seven had tumoral calcinosis. Results: All seven affected children had hyperphosphatemia. There were two subsequent generations comprising thirteen children and seven grandchildren with no instances of tumoral calcinosis. The seven affected patients were followed for as many as forty years and underwent an average of twenty-one operations (range, four to thirty-six operations) for the treatment of calcified lesions. The genetic defect has been identified as the GALNT3 gene, thus leading to the hyperphosphatemic form of the disease. Although two of the patients had died by the time of the present study, the remaining five provided accounts of the disease course, the response to surgery and to medical therapy, and the effect of therapy on their lives. Some members had relatively few lesions and surgical procedures (as few as four), whereas others had an unrelenting course of lesions, recurrences, and surgical procedures (as many as thirty-six, with numerous other procedures). Three patients had multiyear periods with few symptoms-one for seven years, one for twelve years, and one for fifteen years. No effective medical therapy was found to control the lesions, and operations were associated with a high recurrence rate. Conclusions: Familial tumoral calcinosis has a varied natural history; some patients have an unrelenting course, while others may experience quiescent periods. The GALNT3 gene is responsible for the hyperphosphatemic form as seen in this family. Molecular testing may be of benefit to members of affected families, and future studies may help to explain the phenotypic variability among affected individuals. No medical or surgical treatment plan seemed to be effective for controlling the lesions in this family.

UR - http://www.scopus.com/inward/record.url?scp=62549136150&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=62549136150&partnerID=8YFLogxK

U2 - 10.2106/JBJS.G.01512

DO - 10.2106/JBJS.G.01512

M3 - Article

VL - 91

SP - 664

EP - 671

JO - Journal of Bone and Joint Surgery - American Volume

JF - Journal of Bone and Joint Surgery - American Volume

SN - 0021-9355

IS - 3

ER -