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Disease Profile

Insulin-like growth factor I deficiency

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.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

E34.3

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.

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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)

IGF1 deficiency

Categories

Congenital and Genetic Diseases; Endocrine Diseases; Metabolic disorders

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 73272

Definition
Growth delay due to insulin-like growth factor I deficiency is characterised by the association of intrauterine and postnatal growth retardation with sensorineural deafness and intellectual deficit.

Epidemiology
The syndrome is extremely rare and only four cases have been reported in the literature so far.

Clinical description
Addition clinical features include microcephaly, adiposity, and insulin resistance. Partial gonadal dysfunction and osteoporosis may also be present. A case of partial IGF-I deficiency has also been described and was associated with preand postnatal growth retardation and microcephaly but the developmental delay was mild and hearing tests were normal.

Etiology
IGF-I deficiency is caused by homozygous mutations in the insulin-like growth factor 1 gene (IGFI; 12q22-q24.1). IGF-I is essential for foetal and postnatal growth, brain development and metabolism.

Diagnostic methods
Diagnosis relies on direct sequencing of the five IGF1 exons and of the intron-exon junctions. Measurement of IGF-I levels can be used for diagnosis but the circulating levels of IGF-I vary between patients (ranging from undetectable, low to very high) depending on the molecular defect present and on the immunoassay used.

Differential diagnosis
The differential diagnosis should include growth hormone deficiency and growth hormone resistance (caused by GH receptor or STAT5b anomalies), growth delay due to insulin-like growth factor I resistance and primary acid-labile subunit (ALS) deficiency syndrome (see these terms), as well as secondary IGF-I deficiency due to nutritional problems.

Antenatal diagnosis
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.

Genetic counseling
IGF-I deficiency is transmitted as an autosomal recessive trait. Affected families should be offered genetic counselling and informed of a 25% risk of recurrence.

Management and treatment
Management involves nutritional and developmental support, together with screening for deafness. Growth velocity in patients with partial IGF-I deficiency can be increased by recombinant growth hormone (GH) therapy. Recombinant IGF-I therapy can be used in patients with complete IGF-I deficiency or those showing an insufficient response to recombinant GH treatment.

Visit the Orphanet disease page for more resources.

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
80%-99% of people have these symptoms
Abnormal facial shape
Unusual facial appearance
0001999
Attention deficit hyperactivity disorder
Attention deficit
Attention deficit disorder
Attention deficit-hyperactivity disorder
Attention deficits
Childhood attention deficit/hyperactivity disorder

[ more ]

0007018
Bilateral sensorineural hearing impairment
0008619
Congenital sensorineural hearing impairment
0008527
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Insulin resistance
Body fails to respond to insulin
0000855
Intellectual disability, mild
Mental retardation, borderline-mild
Mild and nonprogressive mental retardation
Mild mental retardation

[ more ]

0001256
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Prelingual sensorineural hearing impairment
0000399
Severe intrauterine growth retardation
Severe prenatal growth deficiency
0008846
Severe postnatal growth retardation
Marked growth retardation
Severe growth delay in children
Severe postnatal growth failure

[ more ]

0008850
Short stature
Decreased body height
Small stature

[ more ]

0004322
Small for gestational age
Birth weight less than 10th percentile
Low birth weight

[ more ]

0001518
30%-79% of people have these symptoms
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Delayed eruption of teeth
Delayed eruption
Delayed teeth eruption
Delayed tooth eruption
Eruption, delayed
Late eruption of teeth
Late tooth eruption

[ more ]

0000684
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development

[ more ]

0002750
Hypogonadism
Decreased activity of gonads
0000135
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Neonatal hyperbilirubinemia
0003265
Osteoporosis
0000939
Small placenta
0006266
5%-29% of people have these symptoms
Cafe-au-lait spot
0000957
Concave nasal ridge
Boxer's nasal deformity
Boxer's nose deformity
Saddle nose
Ski jump nose

[ more ]

0011120
Congenital bilateral ptosis
Congenital drooping of both upper eyelids
0007911
Hypoglycemia
Low blood sugar
0001943
Low anterior hairline
Low frontal hairline
Low-set frontal hairline

[ more ]

0000294
Low posterior hairline
Low hairline at back of neck
0002162
Motor delay
0001270
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness

[ more ]

0000545
Prominent forehead
Pronounced forehead
Protruding forehead

[ more ]

0011220
Single transverse palmar crease
0000954
Truncal obesity
0001956
Percent of people who have these symptoms is not available through HPO
Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality

[ more ]

0001939
Autosomal recessive inheritance
0000007
Clinodactyly
Permanent curving of the finger
0030084
Congenital onset
Symptoms present at birth
0003577
Decreased body weight
Decreased weight
Low body weight
Low weight
Weight less than 3rd percentile

[ more ]

0004325
Hyperactivity
More active than typical
0000752
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Osteopenia
0000938
Ptosis
Drooping upper eyelid
0000508
Radial deviation of finger
0009466
Sensorineural hearing impairment
0000407
Short attention span
Poor attention span
Problem paying attention

[ more ]

0000736

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

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 Providing General Support

      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

      • 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 Insulin-like growth factor I deficiency. Click on the link to view a sample search on this topic.