Madelung-like deformity in pseudohypoparathyroidism type 1b

Janine Sanchez, Erasmo Perera, Suzanne M Jan De Beur, Changlin Ding, Anna Dang, Gary D. Berkovitz, Michael A. Levine

Research output: Contribution to journalArticle

Abstract

Context: Pseudohypoparathyroidism (PHP) types 1a and 1b are distinguished by clinical, biochemical, and molecular features. We report extended kindred with PHP 1b in which many affected members also had growth plate defects, including brachydactyly and a Madelung-like deformity. Design: Analyses included clinical examination, assessment of mineral metabolism, thyroid function, skeletal radiography, and analysis of the GNAS and STX16 genes. Setting: Patients were studied in an academic medical center. Results: We studied 37 members of a family in which PHP 1b occurred in 23 individuals. Ten of 17 affected patients who were examined had brachydactyly E, including two subjects with Madelunglike defects. Five of 16 subjects had subclinical hypothyroidism; no subject showed sc ossification or short stature. None of the unaffected members had brachydactyly or an elevated serum level of PTH or TSH. Levels of immunoactive erythrocyte Gα s were normal in two affected subjects tested. Linkage analysis indicated linkage between PTH resistance and the GNAS gene locus; however, no mutations were identified in GNAS exons 1-13. Methylation analysis of genomic DNA from affected subjects showed loss of maternal epigenotype in exon 1A with normal methylation of the differentially methylated regions for XLGαs and NESP55, and PCR demonstrated heterozygosity for a 3.0-kb deletion in the STX16 gene. Conclusion: The segregation of brachydactyly with PHP 1b in this family indicates that an imprinting defect in GNAS can lead to growth plate defects, including brachydactyly and Madelung deformity. These features suggest that GNAS signaling plays a more extensive role in chondrocyte maturation than previously thought.

Original languageEnglish (US)
JournalJournal of Clinical Endocrinology and Metabolism
Volume96
Issue number9
DOIs
StatePublished - Sep 2011

Fingerprint

Brachydactyly
Pseudohypoparathyroidism
Defects
Methylation
Genes
Growth Plate
Exons
Radiography
Metabolism
Minerals
Chondrocytes
Hypothyroidism
Osteogenesis
Thyroid Gland
Erythrocytes
Mothers
Madelung Deformity
Pseudohypoparathyroidism Type 1B
DNA
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Madelung-like deformity in pseudohypoparathyroidism type 1b. / Sanchez, Janine; Perera, Erasmo; Jan De Beur, Suzanne M; Ding, Changlin; Dang, Anna; Berkovitz, Gary D.; Levine, Michael A.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 96, No. 9, 09.2011.

Research output: Contribution to journalArticle

Sanchez, Janine ; Perera, Erasmo ; Jan De Beur, Suzanne M ; Ding, Changlin ; Dang, Anna ; Berkovitz, Gary D. ; Levine, Michael A. / Madelung-like deformity in pseudohypoparathyroidism type 1b. In: Journal of Clinical Endocrinology and Metabolism. 2011 ; Vol. 96, No. 9.
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