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Disease Profile

Pseudopseudohypoparathyroidism

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

All ages

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ICD-10

E20.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

PPHP; Albright hereditary osteodystrophy without multiple hormone resistance; Pseudopseudo-Hypoparathyroidism;

Categories

Congenital and Genetic Diseases; Endocrine Diseases; Eye diseases;

Summary

Pseudopseudohypoparathyroidism (PPHP) is an inherited condition that causes short stature, round face, and short hand bones.[1][2] PPHP causes joints and other soft tissues in the body to harden. It also affects how bones are formed. As a result, PPHP can cause bone, joint, and nerve damage, and this damage can cause lasting pain.[3] Some people with PPHP (10%) also have learning disability.[2] PHPP is caused by mutations in the GNAS gene and is inherited in an autosomal dominant fashion. This condition is usually inherited from the father (genomic imprinting).[1]

PPHP is genetically related to pseudohypoparathyroidism type Ia (PHP-1a). Signs and symptoms are similar, however people with PPHP do not show resistance to parathyroid hormone while people with PHP-1a do. Obesity is characteristic for PHP-1a and may be severe, while obesity is less prominent and may be absent among people with PPHP. Both PHP-1a and PPHP are caused by mutations that affect the function of the GNAS gene. But people who inherit the mutation from their mother develop PHP-1a; whereas those who inherit the mutation from their father develop PPHP.[1]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
5%-29% of people have these symptoms
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Brachydactyly
Short fingers or toes
0001156
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
Delayed eruption of teeth
Delayed eruption
Delayed teeth eruption
Delayed tooth eruption
Eruption, delayed
Late eruption of teeth
Late tooth eruption

[ more ]

0000684
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Full cheeks
Apple cheeks
Big cheeks
Increased size of cheeks
Large cheeks

[ more ]

0000293
Hypoplasia of dental enamel
Underdeveloped teeth enamel
0006297
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Obesity
Having too much body fat
0001513
Osteoporosis
0000939
Pseudohypoparathyroidism
0000852
Round face
Circular face
Round facial appearance
Round facial shape

[ more ]

0000311
Short metacarpal
Shortened long bone of hand
0010049
Short metatarsal
Short long bone of foot
0010743
Short neck
Decreased length of neck
0000470
Short stature
Decreased body height
Small stature

[ more ]

0004322

Diagnosis

Diagnosis of PPHP is based on the presence of features of Albright hereditary osteodystrophy (AHO) without parathyroid hormone (PTH) resistance. If there are features of AHO and resistance to PTH a different form of pseudohypoparathyroidism (PHP) will be considered. Other forms of PHP are usually ruled out by blood tests including serum calcium, phosphate and PTH. X-rays will show shortening of the fourth metacarpal (long bone of the hand) and advanced bone age. All metacarpals and metatarsals (long bones of the foot) may be affected. The diagnosis is confirmed by genetic testing identifying a mutation or change in the GNAS gene. [2][4]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      In-Depth Information

      • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss Pseudopseudohypoparathyroidism. Click on the link to view a sample search on this topic.

        References

        1. Pseudopseudohypoparathyroidism. Online Mendelian Inheritance of Man. November 2010; https://www.ncbi.nlm.nih.gov/omim/612463. Accessed 4/1/2011.
        2. Mantovani G. Pseudopseudohypoparathyroidism. Orphanet. October 2014; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=79445.
        3. Iwase T, Nokura K, Mizuno T, Inagaki T. Spastic tetraparesis in a patient with pseudopseudohypoparathyroidism. J Neurol. 2002 Oct;249(10):1457-8; https://www.ncbi.nlm.nih.gov/pubmed/12532935. Accessed 3/18/2013.
        4. Abraham MR. Pseudohypoparathryroidism Workup. Medscape Reference. December 11 2015; https://emedicine.medscape.com/article/124836-workup.

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