What are the other Names for this Condition? (Also known as/Synonyms)

• Congenital Isolated Hypoparathyroidism
• FIH (Familial Isolated Hypoparathyroidism)
• Inherited Isolated Hypoparathyroidism

What is Familial Isolated Hypoparathyroidism? (Definition/Background Information)

• Familial Isolated Hypoparathyroidism (FIH) is a rare heterogeneous group of metabolic disorders characterized by abnormal calcium metabolism due to deficient secretion of parathormone (PTH), without other endocrine disorders or developmental defects
• It can occur at any age (from the newborn period to adulthood) but generally starts within the first decade of life
• The clinical signs are mainly those of hypocalcemia: myopathy, muscular weakness, cramps, tetany, lenticular cataracts, teeth anomalies and short stature
• FIH may be due to an activating mutation of the calcium-sensing receptor (CASR) gene. This is the most common cause of genetic hypoparathyroidism and is transmitted as an autosomal dominant trait. It represents 42% of isolated hypoparathyroidism cases
• Diagnosis is made when hypocalcemia, hyperphosphoremia, and low or undetectable PTH levels are observed
• Management consists of symptomatic treatment with supplementary calcium and vitamin D

(Source: Familial Isolated Hypoparathyroidism; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Familial Isolated Hypoparathyroidism? (Age and Sex Distribution)

• Familial Isolated Hypoparathyroidism is a rare congenital disorder, with an estimated prevalence of less than 1 in a million
• The presentation of symptoms may occur at any age. However, the signs and symptoms become apparent before a child reaches 10 years of age
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Familial Isolated Hypoparathyroidism? (Predisposing Factors)

• A positive family history may be an important risk factor, since Familial Isolated Hypoparathyroidism can be inherited
• Currently, no other risk factors have been clearly identified for FIH

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Familial Isolated Hypoparathyroidism? (Etiology)

Familial Isolated Hypoparathyroidism may be caused by mutation(s) in CASR, PTH or GCMB genes.

• Mutations in the CASR gene are the most common cause of FIH, accounting for over 40% of all reported cases. The CASR gene mutations are predominantly inherited in an autosomal dominant manner
• The PTH gene mutation(s) causing Familial Isolated Hypoparathyroidism may be inherited in either an autosomal dominant or autosomal recessive manner, while GCMB gene mutations are reported to be transmitted in an autosomal recessive manner

Autosomal dominant inheritance pattern: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Familial Isolated Hypoparathyroidism?

The signs and symptoms of Familial Isolated Hypoparathyroidism may include:

Very frequently present symptoms in 80-99% of the cases:

• Abnormality of calcium-phosphate metabolism
• Hypocalcemia
• Hypoparathyroidism
• Myopathy
• Nephropathy
• Seizures
• Short stature

Frequently present symptoms in 30-79% of the cases:

• Abnormality of dental enamel
• Arrhythmia
• Cataract
• Cerebral calcification
• Delayed eruption of teeth

Occasionally present symptoms in 5-29% of the cases:

• Hyperphosphatemia
• Tetany

(Source: Familial Isolated Hypoparathyroidism; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Familial Isolated Hypoparathyroidism Diagnosed?

Familial Isolated Hypoparathyroidism is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests, including blood tests to check for levels of
  • Parathyroid hormone
  • Calcium
  • Phosphorus
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Familial Isolated Hypoparathyroidism?

The complications of Familial Isolated Hypoparathyroidism may include:

• Problems with movement due to low muscle tone and muscular spasms
• Risk of falls and injuries, if there are sudden and recurrent seizures 
• Low self-esteem as a result of short stature

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Familial Isolated Hypoparathyroidism Treated?

There is no cure for Familial Isolated Hypoparathyroidism, since it is a genetic condition.

• The treatment is usually given to manage the signs and symptoms and any complication that develops
• The treatment may include calcium and Vitamin D supplements
• Intake of foods rich in calcium (such as breakfast cereals, orange juice and leafy vegetables) is highly recommended
• FDA-approved recombinant parathyroid hormone injection (teriparatide)

How can Familial Isolated Hypoparathyroidism be Prevented?

Currently, Familial Isolated Hypoparathyroidism may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Familial Isolated Hypoparathyroidism? (Outcomes/Resolutions)

• The prognosis of Familial Isolated Hypoparathyroidism is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Familial Isolated Hypoparathyroidism:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/