Insulin-like growth factor I deficiency

Other Names: IGF1 deficiency; Growth retardation with sensorineural deafness and mental retardation

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.

Cause

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.

Inheritance

Autosomal recessive inheritance, a 25% chance

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.

Signs and symptoms

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 pre- and postnatal growth retardation and microcephaly but the developmental delay was mild and hearing tests were normal.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Abnormal facial shape(Unusual facial appearance)
• Attention deficit hyperactivity disorder(Attention deficit)
• Bilateral sensorineural hearing impairment
• Congenital sensorineural hearing impairment
• Failure to thrive(Faltering weight)
• Insulin resistance(Body fails to respond to insulin)
• Intellectual disability, mild(Mental retardation, borderline-mild)
• Microcephaly(Abnormally small skull)
• Prelingual sensorineural hearing impairment
• Severe intrauterine growth retardation(Severe prenatal growth deficiency)
• Severe postnatal growth retardation(Marked growth retardation)
• Short stature(Decreased body height)
• Small for gestational age(Birth weight less than 10th percentile)

30%-79% of people have these symptoms

• Clinodactyly of the 5th finger(Permanent curving of the pinkie finger)
• Delayed eruption of teeth(Delayed eruption)
• Delayed skeletal maturation(Delayed bone maturation)
• Hypogonadism(Decreased activity of gonads)
• Micrognathia(Little lower jaw)
• Neonatal hyperbilirubinemia
• Osteoporosis
• Small placenta

5%-29% of people have these symptoms

• Cafe-au-lait spot
• Concave nasal ridge(Boxer's nasal deformity)
• Congenital bilateral ptosis(Congenital drooping of both upper eyelids)
• Hypoglycemia(Low blood sugar)
• Low anterior hairline(Low frontal hairline)
• Low posterior hairline(Low hairline at back of neck)
• Motor delay
• Myopia(Close sighted)
• Prominent forehead(Pronounced forehead)
• Single transverse palmar crease
• Truncal obesity

Diagnosis

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.

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.

NIH genetic and rare disease info

• NIH info on Insulin-like growth factor I deficiency

Insulin-like growth factor I deficiency is a rare disease.

Insulin-like growth factor I deficiency Resources
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