• A molecular basis for many forms of Primary IGFD has now been identified. • Disorders of the GH receptor can have low levels of GHBP (as in most defects of the extracellular domain of the GH receptor), or normal levels of GHBP (as in defects of the transmembrane and intracellular domains) • A growth phenotype similar to that seen in defects of the GH receptor has been observed in patients with post-receptor defects resulting from mutations of the gene for STAT5b. • Defects of the IGF-I gene can result in absence of serum IGF-I (IGF-I gene deletion) or elevated IGF-I (missense mutations resulting in bioinactive IGF-I). • Low serum concentrations of IGF-I and IGFBP-3, accompanied by modest growth failure, have been observed in mutations of the gene for ALS.