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Macrosomia, obesity, and macrocephaly as first clinical presentation of PHP1b caused by STX16 deletion
Author(s) -
de Lange Iris M.,
Verrijn Stuart Annemarie A.,
van der Luijt Rob B.,
Ploos van Amstel Hans Kristian,
van Haelst Mieke M.
Publication year - 2016
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37818
Subject(s) - gnas complex locus , pseudohypoparathyroidism , macrocephaly , endocrinology , medicine , parathyroid hormone , imprinting (psychology) , exon , biology , gene , genetics , pediatrics , calcium
Pseudohypoparathyroidism (PHP) is a genetic disorder with resistance to parathyroid hormone (PTH) as most important feature. Main subtypes of the disease are pseudohypoparathyroidism 1b (PHP1b) and pseudohypoparathyroidism 1a (PHP1a). PHP1b is characterized by PTH resistance of the renal cortex due to reduced activity of the stimulatory G protein α subunit (Gsα) of the PTH receptor. In addition to resistance to PTH, PHP1a patients also lack sensitivity for other hormones that signal their actions through G protein‐coupled receptors and display physical features of Albright hereditary osteodystrophy (AHO), which is not classically seen in PHP1b patients. PHP1a is caused by heterozygous loss‐of‐function mutations in maternally inherited GNAS exons 1–13, which encode Gsα. PHP1b is often caused by deletion of the STX16 gene, which is thought to have an important role in controlling the methylation and thus imprinting at part of the GNAS locus. Here we present a patient with PHP1b caused by the previously described recurrent 3‐kb STX16 deletion. The patient's first symptoms were macrosomia, early onset obesity, and macrocephaly. Since this is an atypical but previously described rare presentation of PHP1b, we reemphasize STX16 deletions and PHP1b as a rare cause for early onset obesity and macrosomia. © 2016 Wiley Periodicals, Inc.