Macrosomia, obesity, and macrocephaly as first clinical presentation of PHP1b caused by STX16 deletion
Iris M de Lange1, Annemarie A Verrijn Stuart2, Rob B van der Luijt1
1Department of Medical Genetics, University Medical Centre, Utrecht, The Netherlands.
Insights
Pseudohypoparathyroidism type 1b (PHP1b) can present with macrosomia, obesity, and macrocephaly due to STX16 deletions. This highlights PHP1b as a rare cause of these early-onset symptoms.
Area of Science:
- Genetics
- Endocrinology
- Molecular Biology
Background:
- Pseudohypoparathyroidism (PHP) is a genetic disorder characterized by parathyroid hormone (PTH) resistance.
- PHP subtypes include PHP1b and PHP1a, differing in hormone resistance and physical manifestations.
- PHP1a involves GNAS mutations, while PHP1b is often linked to STX16 deletions affecting GNAS imprinting.
Observation:
- This report details a patient with PHP1b caused by a recurrent 3-kb STX16 deletion.
- The patient exhibited macrosomia, early-onset obesity, and macrocephaly, which are atypical symptoms for PHP1b.
- These findings represent a rare but documented presentation of PHP1b.
Findings:
- The study confirms a link between STX16 deletions and PHP1b.
- The case demonstrates that PHP1b can manifest with macrosomia, early-onset obesity, and macrocephaly.
- This atypical presentation underscores the importance of considering genetic factors in diagnosing such conditions.
Implications:
- STX16 deletions should be considered in the differential diagnosis of early-onset obesity and macrosomia.
- Recognizing rare PHP1b presentations can lead to earlier diagnosis and management.
- Further research into GNAS imprinting and STX16 gene function is warranted.
Abstract:
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.
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