2q37 deletions in patients with an albright hereditary osteodystrophy phenotype and PTH resistance

Francesca Marta Elli, Luisa de Sanctis, Bruno Madeo, Maria A. Maffini, Paolo Bordogna, Arianna Pirelli, Maura Arosio, Giovanna Mantovani

Research output: Contribution to journalArticle

Abstract

Pseudohypoparathyroidism (PHP) is a rare endocrine disorder derived from the defective activation of the cAMP pathway by the parathyroid hormone secondary to GNAS molecular defects. PHP subtypes are defined by the presence/absence of specific clinical/biochemical features. PHP1A is characterized by resistance to multiple hormones with features of Albright hereditary osteodystrophy (AHO), while pseudopseudohypoparathyroidism (PPHP) is characterized by AHO in the absence of PTH resistance. Small subsets of PHP and PPHP patients without known molecular defects have been re-diagnosed as being affected by the brachydactyly-mental retardation syndrome (BDMR), also known as the AHO-like syndrome. This study aimed to analyse 24 PHP1A and 51 PPHP patients without a molecular diagnosis for the presence of BDMR-associated 2q37 deletions to improve the differential diagnosis and to identify features that might help to avoid a misdiagnosis. Molecular investigations identified 4 deletions in 4 unrelated patients. The affected patients showed a combination of the most pathognomonic AHO features. Of note, 3 of the patients also displayed mild PTH resistance, and none of the patients developed ectopic ossifications. Our work confirmed the rarity of the misdiagnosis of BDMR in PHP patients through the identification of 4 patients bearing a 2q37 deletion in a cohort of 73 PHP patients (5.3%). Three patients with the deletion presented a PHP1A phenotype in the absence of any BDMR-specific findings. Further studies on larger case series are needed to elucidate the overlap between these clinical entities and to allow the early identification of patients.

Original languageEnglish
Article number604
JournalFrontiers in Endocrinology
Volume10
Issue numberAUG
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Phenotype
Pseudohypoparathyroidism
Pseudopseudohypoparathyroidism
Diagnostic Errors
Albright's hereditary osteodystrophy
Chromosome 2q37 deletion syndrome
Heterotopic Ossification
Parathyroid Hormone
Differential Diagnosis
Hormones

Keywords

  • 2q37 deletion
  • Albright hereditary osteodystrophy
  • Brachydactyly-mental retardation syndrome
  • GNAS
  • Pseudohypoparathyroidism

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

2q37 deletions in patients with an albright hereditary osteodystrophy phenotype and PTH resistance. / Elli, Francesca Marta; de Sanctis, Luisa; Madeo, Bruno; Maffini, Maria A.; Bordogna, Paolo; Pirelli, Arianna; Arosio, Maura; Mantovani, Giovanna.

In: Frontiers in Endocrinology, Vol. 10, No. AUG, 604, 01.01.2019.

Research output: Contribution to journalArticle

Elli, Francesca Marta ; de Sanctis, Luisa ; Madeo, Bruno ; Maffini, Maria A. ; Bordogna, Paolo ; Pirelli, Arianna ; Arosio, Maura ; Mantovani, Giovanna. / 2q37 deletions in patients with an albright hereditary osteodystrophy phenotype and PTH resistance. In: Frontiers in Endocrinology. 2019 ; Vol. 10, No. AUG.
@article{b324adb7d0084b29a8acb82134751cb7,
title = "2q37 deletions in patients with an albright hereditary osteodystrophy phenotype and PTH resistance",
abstract = "Pseudohypoparathyroidism (PHP) is a rare endocrine disorder derived from the defective activation of the cAMP pathway by the parathyroid hormone secondary to GNAS molecular defects. PHP subtypes are defined by the presence/absence of specific clinical/biochemical features. PHP1A is characterized by resistance to multiple hormones with features of Albright hereditary osteodystrophy (AHO), while pseudopseudohypoparathyroidism (PPHP) is characterized by AHO in the absence of PTH resistance. Small subsets of PHP and PPHP patients without known molecular defects have been re-diagnosed as being affected by the brachydactyly-mental retardation syndrome (BDMR), also known as the AHO-like syndrome. This study aimed to analyse 24 PHP1A and 51 PPHP patients without a molecular diagnosis for the presence of BDMR-associated 2q37 deletions to improve the differential diagnosis and to identify features that might help to avoid a misdiagnosis. Molecular investigations identified 4 deletions in 4 unrelated patients. The affected patients showed a combination of the most pathognomonic AHO features. Of note, 3 of the patients also displayed mild PTH resistance, and none of the patients developed ectopic ossifications. Our work confirmed the rarity of the misdiagnosis of BDMR in PHP patients through the identification of 4 patients bearing a 2q37 deletion in a cohort of 73 PHP patients (5.3{\%}). Three patients with the deletion presented a PHP1A phenotype in the absence of any BDMR-specific findings. Further studies on larger case series are needed to elucidate the overlap between these clinical entities and to allow the early identification of patients.",
keywords = "2q37 deletion, Albright hereditary osteodystrophy, Brachydactyly-mental retardation syndrome, GNAS, Pseudohypoparathyroidism",
author = "Elli, {Francesca Marta} and {de Sanctis}, Luisa and Bruno Madeo and Maffini, {Maria A.} and Paolo Bordogna and Arianna Pirelli and Maura Arosio and Giovanna Mantovani",
year = "2019",
month = "1",
day = "1",
doi = "10.3389/fendo.2019.00604",
language = "English",
volume = "10",
journal = "Frontiers in Endocrinology",
issn = "1664-2392",
publisher = "Frontiers Media S. A.",
number = "AUG",

}

TY - JOUR

T1 - 2q37 deletions in patients with an albright hereditary osteodystrophy phenotype and PTH resistance

AU - Elli, Francesca Marta

AU - de Sanctis, Luisa

AU - Madeo, Bruno

AU - Maffini, Maria A.

AU - Bordogna, Paolo

AU - Pirelli, Arianna

AU - Arosio, Maura

AU - Mantovani, Giovanna

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Pseudohypoparathyroidism (PHP) is a rare endocrine disorder derived from the defective activation of the cAMP pathway by the parathyroid hormone secondary to GNAS molecular defects. PHP subtypes are defined by the presence/absence of specific clinical/biochemical features. PHP1A is characterized by resistance to multiple hormones with features of Albright hereditary osteodystrophy (AHO), while pseudopseudohypoparathyroidism (PPHP) is characterized by AHO in the absence of PTH resistance. Small subsets of PHP and PPHP patients without known molecular defects have been re-diagnosed as being affected by the brachydactyly-mental retardation syndrome (BDMR), also known as the AHO-like syndrome. This study aimed to analyse 24 PHP1A and 51 PPHP patients without a molecular diagnosis for the presence of BDMR-associated 2q37 deletions to improve the differential diagnosis and to identify features that might help to avoid a misdiagnosis. Molecular investigations identified 4 deletions in 4 unrelated patients. The affected patients showed a combination of the most pathognomonic AHO features. Of note, 3 of the patients also displayed mild PTH resistance, and none of the patients developed ectopic ossifications. Our work confirmed the rarity of the misdiagnosis of BDMR in PHP patients through the identification of 4 patients bearing a 2q37 deletion in a cohort of 73 PHP patients (5.3%). Three patients with the deletion presented a PHP1A phenotype in the absence of any BDMR-specific findings. Further studies on larger case series are needed to elucidate the overlap between these clinical entities and to allow the early identification of patients.

AB - Pseudohypoparathyroidism (PHP) is a rare endocrine disorder derived from the defective activation of the cAMP pathway by the parathyroid hormone secondary to GNAS molecular defects. PHP subtypes are defined by the presence/absence of specific clinical/biochemical features. PHP1A is characterized by resistance to multiple hormones with features of Albright hereditary osteodystrophy (AHO), while pseudopseudohypoparathyroidism (PPHP) is characterized by AHO in the absence of PTH resistance. Small subsets of PHP and PPHP patients without known molecular defects have been re-diagnosed as being affected by the brachydactyly-mental retardation syndrome (BDMR), also known as the AHO-like syndrome. This study aimed to analyse 24 PHP1A and 51 PPHP patients without a molecular diagnosis for the presence of BDMR-associated 2q37 deletions to improve the differential diagnosis and to identify features that might help to avoid a misdiagnosis. Molecular investigations identified 4 deletions in 4 unrelated patients. The affected patients showed a combination of the most pathognomonic AHO features. Of note, 3 of the patients also displayed mild PTH resistance, and none of the patients developed ectopic ossifications. Our work confirmed the rarity of the misdiagnosis of BDMR in PHP patients through the identification of 4 patients bearing a 2q37 deletion in a cohort of 73 PHP patients (5.3%). Three patients with the deletion presented a PHP1A phenotype in the absence of any BDMR-specific findings. Further studies on larger case series are needed to elucidate the overlap between these clinical entities and to allow the early identification of patients.

KW - 2q37 deletion

KW - Albright hereditary osteodystrophy

KW - Brachydactyly-mental retardation syndrome

KW - GNAS

KW - Pseudohypoparathyroidism

UR - http://www.scopus.com/inward/record.url?scp=85072730128&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072730128&partnerID=8YFLogxK

U2 - 10.3389/fendo.2019.00604

DO - 10.3389/fendo.2019.00604

M3 - Article

AN - SCOPUS:85072730128

VL - 10

JO - Frontiers in Endocrinology

JF - Frontiers in Endocrinology

SN - 1664-2392

IS - AUG

M1 - 604

ER -