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

• Congenital IGHD Disorder
• Congenital Isolated GH Deficiency Disorder
• Non-Acquired Isolated Growth Hormone Deficiency Disorder

What is Isolated Growth Hormone Deficiency Disorder? (Definition/Background Information)

• Isolated Growth Hormone Deficiency (IGHD) Disorder is a condition caused by a severe shortage or absence of growth hormone without other hormonal problems
• The growth hormone is a protein necessary for normal growth of the bone and body tissues. Because people with this condition do not have enough of this hormone, they have short stature, which is noticeable from early childhood
• There are basically four different types of isolated growth hormone deficiency, which are classified by the severity of the symptoms, the cause and the inheritance: 
• Isolated Growth Hormone Deficiency type IA
• Isolated Growth Hormone Deficiency type IB
• Isolated Growth Hormone Deficiency type II 
• Isolated Growth Hormone Deficiency type III
• Treatment involves giving growth hormone to those who are affected

(Source: Isolated Growth Hormone Deficiency Disorder; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

The characteristics of the 4 subtypes of Isolated Growth Hormone Deficiency Disorder are as follow:

• Isolated Growth Hormone Deficiency type IA: The most severe type is caused by mutation(s) in the GH1 gene and results in absence of growth hormone
• Isolated Growth Hormone Deficiency type IB: There are low levels of growth hormone present, and the condition is caused either by GH1 or GHRHR gene mutations
• Isolated Growth Hormone Deficiency type II: With very low levels of growth hormone and under-developed pituitary gland, this type is caused by mutations in the GH1 gene
• Isolated Growth Hormone Deficiency type III: It is caused by mutation(s) in the BTK gene, with low levels of growth hormone. In addition, affected individuals also have a weak immune system

Who gets Isolated Growth Hormone Deficiency Disorder? (Age and Sex Distribution)

• Isolated Growth Hormone Deficiency Disorder is a rare congenital disorder
• The age at presentation of symptoms may vary, depending on the type of IGHD Disorder
• Type IA: Infancy
• Type 1B: Mid-childhood
• Types II and III: Early- to mid-childhood
• Both males and females may be affected by all types with the exception of type III, which predominantly occurs in males
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Isolated Growth Hormone Deficiency Disorder? (Predisposing Factors)

• A positive family history may be an important risk factor, since Isolated Growth Hormone Deficiency Disorder can be inherited
• Currently, no other risk factors have been clearly identified for this deficiency disorder

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 Isolated Growth Hormone Deficiency Disorder? (Etiology)

The different types of Isolated Growth Hormone Deficiency Disorder may be caused by different gene mutation(s) and can be inherited differently as well.

• Isolated Growth Hormone Deficiency type IA is caused by mutation(s) in the GH1 gene and inherited in an autosomal recessive manner
• Isolated Growth Hormone Deficiency type IB is caused either by GH1 or GHRHR gene mutations, and is also inherited in an autosomal recessive manner
• Isolated Growth Hormone Deficiency type II is caused by mutations in the GH1 gene, and can be inherited in an autosomal dominant manner. This type of the disorder can also develop spontaneously due to new mutations
• Isolated Growth Hormone Deficiency type III is caused by mutation(s) in the BTK gene, and is inherited in an X-linked recessive pattern

Autosomal recessive mode of 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).

Autosomal dominant pattern of inheritance: 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.

X-linked recessive mode of inheritance: The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

What are the Signs and Symptoms of Isolated Growth Hormone Deficiency Disorder?

The signs and symptoms of Isolated Growth Hormone Deficiency Disorder may vary among affected individuals in type and severity, and include:

• Anterior hypopituitarism
• Delayed skeletal maturation
• Short stature

(Source: Isolated Growth Hormone Deficiency Disorder; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

• Frequent infections in type III
• Delayed eruption of teeth
• Poor growth of nails
• Increased cholesterol and LDL levels in blood

How is Isolated Growth Hormone Deficiency Disorder Diagnosed?

Isolated Growth Hormone Deficiency Disorder is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• 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 Isolated Growth Hormone Deficiency Disorder?

The complications of Isolated Growth Hormone Deficiency Disorder may include:

• Delay or failure to reach developmental milestones
• Tissue scarring due to frequent infections
• Truncal obesity
• Low self-esteem due to one’s appearance
• Depression and anxiety

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

How is Isolated Growth Hormone Deficiency Disorder Treated?

There is no cure for Isolated Growth Hormone Deficiency Disorder, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops. The treatment methods may include 

• Growth hormone supplementation
• Antibiotics for infections

How can Isolated Growth Hormone Deficiency Disorder be Prevented?

Isolated Growth Hormone Deficiency Disorder 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), if available, 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 Isolated Growth Hormone Deficiency Disorder? (Outcomes/Resolutions)

• The prognosis of Isolated Growth Hormone Deficiency Disorder is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions and late-onset of disease generally fare better have better than those with severe symptoms and early-onset disease 
• It has been reported that without growth hormone treatment, the lifespan of those affected may be shortened

Additional and Relevant Useful Information for Isolated Growth Hormone Deficiency Disorder:

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

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