Pseudohypoparathyroidism type 1B

What causes pseudohypoparathyroidism type 1B (PHP1B)?

PHP1B is a complex genetic disorder that may be caused by various types of changes in genes or chromosomes. While there are several different PHP1B subtypes, they all appear to somehow be associated with methylation changes involving the region of the GNAS gene.

Methylation is a chemical reaction that attaches small molecules called methyl groups to certain segments of DNA. Abnormal methylation can disrupt the normal activity of genes. For example, for genes that are only "active" when inherited from a certain parent, methylation is one way that a gene's parent of origin is "marked" during the formation of egg and sperm cells. Changes that affect the activation and deactivation of genes without any change in the underlying DNA sequence are called epigenetic changes.

Epigenetic changes involving PHP1B can be caused by a maternal deletion in the GNAS or STX16 gene, by paternal uniparental isodisomy of chromosome 20q (patUPD20q) or by undefined genetic mutations. The GNAS methylation changes are ultimately responsible for resistance to PTH signals in part of the kidneys, leading to the features of PHP1B.

Last updated on 05-01-20

How is pseudohypoparathyroidism type 1B (PHP1B) diagnosed?

The diagnosis of PHP1B is generally based on clinical features (signs, symptoms, and physical exams) and biochemical findings from a blood test for calcium-phosphate metabolism. This blood test includes measurements of calcium, phosphate, magnesium, and parathyroid hormone (PTH) in order to distinguish PHP from other conditions. PHP1B can be distinguished from other types of PHP by the absence of Albright's hereditary osteodystrophy. Molecular genetic testing can confirm the diagnosis.

Last updated on 05-01-20

Is pseudohypoparathyroidism type 1B (PHP1B) inherited?

PHP1B is most often sporadic (not inherited), occurring in people with no family history of PHP1B. However, sex-influenced autosomal dominant inheritance, from mother to child, has been reported. When a trait is sex- influenced, it means that the trait is expressed differently depending on whether it is inherited from a person's mother or father. This phenomenon is known as genomic imprinting.

In familial cases of PHP1B, it appears that parathyroid hormone (PTH) resistance in PHP1B develops only after maternal inheritance of the genetic change, whereas paternal inheritance is not associated with PTH resistance or other endocrine abnormalities. In several families with PHP1B, it has been reported that the disorder only occurred if the genetic change was inherited from the mother.

The genetics of PHP1B is extremely complex. The disorder may be caused by various types of genetic or epigenetic changes. Because the signs and symptoms of the sporadic and autosomal dominant forms of PHP1B are similar, identifying the specific genetic cause in each case is important for determining genetic risks to other family members.

People with personal questions or concerns about the inheritance of PHP1B, or genetic testing, are strongly encouraged to speak with a genetic counselor or other genetics professional. A genetics professional can help by:

  • thoroughly evaluating the family history
  • addressing questions and concerns
  • assessing recurrence risks
  • facilitating genetic testing if desired
  • discussing prenatal testing and management options

Last updated on 05-01-20

Name: HypoPARAthyroidism Association, Inc. HPTH P.O. Box 2258
Idaho Falls, ID, 83403, United States
Phone: +1-208-524-3857 Toll Free: 866-213-0394 Email: Url:
Name: Hormone Health Network United States Toll Free: 1-800-HORMONE (1-800-467-6663) Email: Url:
Name: The Endocrine Society 8401 Connecticut Avenue, Suite 900
Chevy Chase, MD, 20815, United States
Phone: 301–941–0200 Toll Free: 888–363–6274 Fax : 301–941–0259 Email: Url:
Name: American Thyroid Association 6066 Leesburg Pike, Suite 550
Falls Church, VA, 22041, United States
Phone: 703–998–8890 Toll Free: 800–THYROID (849–7643) Fax : 703–998–8893 Email: Url:
Name: Hypopara UK 6 The Meads East Grinstead
West Sussex, RH19 4DF, United Kingdom
Phone: 01342 316315 Email: Url:

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