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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.
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.
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.
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.
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.
Source: GARD Last updated on 05-01-20
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