Rare Pediatrics News

Disease Profile

Insulin-like growth factor 1 resistance to

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.


US Estimated

Europe Estimated

Age of onset






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


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.


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.


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


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.


Not applicable


Other names (AKA)

Somatomedin end-organ insensitivity to; Somatomedin-c resistance to; IGF-1 resistance


Congenital and Genetic Diseases; Endocrine Diseases


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

Orpha Number: 73273

Growth delay due to IGF-I resistance is characterised by variable intrauterine and postnatal growth retardation and elevated serum IGF-I levels. Addition features include variable degrees of intellectual deficit, microcephaly and dysmorphism (broad nasal bridge and tip, smooth philtrum, thin upper and everted lower lips, short fingers, clinodactyly, wide-set nipples and pectus excavatum).

Prevalence is unknown.

IGF-I resistance may be caused by a variety of genetic defects: ring chromosome 15, distal heterozygous 15q deletions encompassing the IGF1R gene (15q26.3), or IGF1R gene mutations. Intellectual deficit is pronounced in patients with ring chromosome 15 but varies depending on the size of the deletion and on the functions of other deleted genes in patients with 15q deletions. Partial IGF-I insensitivity due to IGF1R haploinsufficiency has been reported in one patient with a small deletion encompassing one allele of the IGF1R gene and was characterised by small size for gestational age, persistent growth failure that improved considerably with GH therapy, and the absence of intellectual deficit. IGF1R mutations have been described in six patients so far and were associated with variable growth delay and degrees of intellectual deficit.

Diagnostic methods
Diagnosis relies on karyotyping for detection of ring chromosome 15, detection of small deletions encompassing IGF1R and detection of IGF1R mutations by sequence variation screening methods or by direct sequencing of the 21 IGF1R exons and their intron-exon junctions.

Differential diagnosis
The differential diagnosis should include bio-inactive IGF-I resulting in IGF-I deficiency (see this term). Measurement of IGF-I levels can be used for diagnosis but circulating levels of IGF-I may vary over time for the same patient and may not be elevated in case of poor nutritional status.

Antenatal diagnosis
Prenatal diagnosis has not been reported and is complicated by the variable expressivity (even within the same family) of some of the reported mutations, especially in terms of their impact on intellectual development.

Genetic counseling
In all but one of these patients, the mutations were heterozygous and transmitted as an autosomal dominant trait. Affected families should be offered genetic counselling and informed of a 50% risk of recurrence for dominant inheritance and of a 25% risk of recurrence for recessive transmission.

Management and treatment
Management involves nutritional and developmental support. Although deafness has not yet been reported in patients with IGF-I resistance, it is present in some patients with IGF-I deficiency (caused by mutations in the gene encoding the IGF1R ligand, IGFI). As a result, screening for deafness should be proposed for all patients with IGF-I resistance. Some patients with IGF-I resistance show increased growth velocity with recombinant GH therapy while others show no response.

Prognosis varies depending on the underlying molecular anomaly.

Visit the Orphanet disease page for more resources.


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:
80%-99% of people have these symptoms
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development

[ more ]

Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

Short stature
Decreased body height
Small stature

[ more ]

30%-79% of people have these symptoms
Broad nasal tip
Broad tip of nose
Broad, upturned nose
Increased breadth of nasal tip
Increased breadth of tip of nose
Increased width of nasal tip
Increased width of tip of nose
Nasal tip, broad
Nasal tip, wide
Wide tip of nose

[ more ]

Permanent curving of the finger
Everted lower lip vermilion
Drooping lower lip
Outward turned lower lip

[ more ]

Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific

[ more ]

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

[ more ]

Motor delay
Pectus excavatum
Funnel chest
Short palm
Smooth philtrum
Thin vermilion border
Decreased volume of lip
Thin lips

[ more ]

Wide intermamillary distance
Widely spaced nipples
Wide-spaced nipples
Widely-spaced nipples

[ more ]

Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]

Percent of people who have these symptoms is not available through HPO
Abnormal rib cage morphology
Abnormality of the rib cage
Excessive, persistent worry and fear
Autosomal dominant inheritance
Autosomal recessive inheritance
Congenital onset
Symptoms present at birth
Decreased body weight
Decreased weight
Low body weight
Low weight
Weight less than 3rd percentile

[ more ]

Deeply set eye
Deep set eye
Deep-set eyes
Sunken eye

[ more ]

Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay

[ more ]

Diabetes mellitus
Global developmental delay
High palate
Elevated palate
Increased palatal height

[ more ]

High pitched voice
Highly arched eyebrow
Arched eyebrows
Broad, arched eyebrows
High, rounded eyebrows
High-arched eyebrows
Thick, flared eyebrows

[ more ]

Hypoplasia of the corpus callosum
Underdevelopment of part of brain called corpus callosum
Increased serum insulin-like growth factor 1
Inability to make and keep healthy fat tissue
Long philtrum
Low-set ears
Low set ears
Lowset ears

[ more ]

Little lower jaw
Small jaw
Small lower jaw

[ more ]

Narrow mouth
Small mouth
Patent foramen ovale
Radial deviation of finger
Reduced subcutaneous adipose tissue
Reduced fat tissue below the skin
Receding chin
Receding lower jaw
Weak chin
Weak jaw

[ more ]

Rieger anomaly
Sandal gap
Gap between 1st and 2nd toes
Gap between first and second toe
Increased space between first and second toes
Sandal gap between first and second toes
Wide space between 1st, 2nd toes
Wide space between first and second toes
Wide-spaced big toe
Widely spaced 1st-2nd toes
Widely spaced first and second toes
Widened gap 1st-2nd toes
Widened gap first and second toe

[ more ]

Short foot
Short feet
Small feet

[ more ]

Small hand
Disproportionately small hands
Sparse scalp hair
Reduced/lack of hair on scalp
Scalp hair, thinning
Sparse, thin scalp hair
sparse-absent scalp hair

[ more ]

Squint eyes

[ more ]


[ more ]

Triangular face
Face with broad temples and narrow chin
Triangular facial shape

[ more ]



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.

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 1 resistance to. Click on the link to view a sample search on this topic.

Rare Pediatrics News

fascinating Rare disease knowledge right in your inbox
Subscribe to receive