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

• Growth Retardation with Sensorineural Deafness and Mental Retardation
• IGF1 Deficiency Disorder

What is Insulin-like Growth Factor I Deficiency Disorder? (Definition/Background Information)

• Growth delay due to Insulin-like Growth Factor I Deficiency is characterized by the association of intrauterine and postnatal growth retardation with sensorineural deafness and intellectual deficit
• Additional clinical features of Insulin-like Growth Factor I Deficiency Disorder include microcephaly, adiposity, and insulin resistance. Partial gonadal dysfunction and osteoporosis may also be present
• Prenatal diagnosis is feasible for families with an identified IGF1 mutation proven to be responsible for the disease phenotype of intrauterine and postnatal growth delay associated with intellectual deficit
• IGF-I Deficiency Disorder is transmitted as an autosomal recessive trait. Affected families should be offered genetic counselling and informed of a 25% risk of recurrence

(Source: Insulin-like Growth Factor I Deficiency; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Insulin-like Growth Factor I Deficiency Disorder? (Age and Sex Distribution)

• Insulin-like Growth Factor I Deficiency Disorder is an extremely rare congenital disorder, with only 4 cases reported thus far in the medical literature
• The presentation of symptoms may occur at birth
• Both males and females may be affected

What are the Risk Factors for Insulin-like Growth Factor I Deficiency Disorder? (Predisposing Factors)

• A positive family history may be an important risk factor, since Insulin-like Growth Factor I Deficiency Disorder can be inherited
• Children born to consanguineous parents may bear an increased risk for IGF-I 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 Insulin-like Growth Factor I Deficiency Disorder? (Etiology)

• Insulin-like Growth Factor I Deficiency Disorder is caused by mutation(s) in the IGF-1 gene, which codes for the insulin-like growth factor-I
• This growth factor is essential for growth, brain development, and metabolism before and after birth
• The condition is inherited in an autosomal recessive manner

Autosomal recessive pattern 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).

What are the Signs and Symptoms of Insulin-like Growth Factor I Deficiency Disorder?

The signs and symptoms of Insulin-like Growth Factor I Deficiency Disorder may include:

• Abnormality of metabolism/homeostasis
• Clinodactyly
• Decreased body weight
• Hyperactivity
• Intellectual disability
• Intrauterine growth retardation
• Osteopenia
• Ptosis
• Radial deviation of finger
• Sensorineural hearing impairment
• Short attention span

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

• Abnormal facial shape
• Attention deficit hyperactivity disorder
• Bilateral sensorineural hearing impairment
• Congenital sensorineural hearing impairment
• Failure to thrive
• Insulin resistance
• Intellectual disability, mild
• Microcephaly
• Prelingual sensorineural hearing impairment
• Severe intrauterine growth retardation
• Severe postnatal growth retardation
• Short stature
• Small for gestational age

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

• Clinodactyly of the 5th finger
• Delayed eruption of teeth
• Delayed skeletal maturation
• Hypogonadism
• Micrognathia
• Osteoporosis
• Neonatal hyperbilirubinemia
• Small placenta

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

• Cafe-au-lait spot
• Concave nasal ridge
• Congenital bilateral ptosis
• Hypoglycemia
• Low anterior hairline
• Low posterior hairline
• Motor delay
• Myopia
• Prominent forehead
• Single transverse palmar crease
• Truncal obesity

(Source: Insulin-like Growth Factor I Deficiency; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Insulin-like Growth Factor I Deficiency Disorder Diagnosed?

Insulin-like Growth Factor I 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
• Prenatal ultrasound examination of a developing fetus to check for intra-uterine growth retardation
• Molecular genetic testing to check for or confirm causative mutation(s) in the IGF-1 gene
• Differential diagnosis to rule out conditions that may present with symptoms similar to Insulin-like Growth Factor I Deficiency Disorder (Examples: Growth hormone deficiency, growth hormone resistance and growth delay due to insulin-like growth factor I resistance, among others)

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 Insulin-like Growth Factor I Deficiency Disorder?

The complications of Insulin-like Growth Factor I Deficiency Disorder may include:

• Deafness
• Delay in reaching developmental milestones
• Potential for bone fractures, which may be caused by osteoporosis
• Low self-esteem due to short stature

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

How is Insulin-like Growth Factor I Deficiency Disorder Treated?

There is no cure for Insulin-like Growth Factor I 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 methods for efficient management of this genetic condition may include:

• Nutritional support
• Recombinant growth hormone therapy
• Recombinant IGF-1 therapy

How can Insulin-like Growth Factor I Deficiency Disorder be Prevented?

Currently, Insulin-like Growth Factor I 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) 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 Insulin-like Growth Factor I Deficiency Disorder? (Outcomes/Resolutions)

• The prognosis of Insulin-like Growth Factor I Deficiency Disorder 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 Insulin-like Growth Factor I Deficiency Disorder:

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

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