Table 2.
Summary of Phenotypic and Biochemical Features in the Range of Genetic Defects Causing Mild GH Insensitivity
| Phenotype |
Gene Defect
|
||||||
|---|---|---|---|---|---|---|---|
| GHR Heterozygous Dominant Negative | GHR Pseudoexon | STAT5B Heterozygous Dominant Negative | IGFI | IGF2 (Heterozygous Variants) | IGFALS | PAPPA2 | |
| Severe growth failure | +/− | +/− | + | + | + | – | – |
| Midface hypoplasia | – | * | +/− | – | – | – | – |
| Other facial dysmorphism | – | – | – | + | + | – | + |
| Deafness | – | – | – | +/− | – | – | – |
| Microcephaly | – | – | – | + | – | – | +/− |
| Intellectual delay | – | – | – | + | – | – | – |
| Pubertal delay | – | – | +/− | – | – | + | – |
| Immune deficiency | – | – | + | – | – | – | – |
| Hypoglycemia | – | + | −/+ | – | n/r | – | – |
| Hyperinsulinemia | – | – | – | +/− | n/r | + | + |
| IGF-1 | ↓ | n/↓ | ↓ | n/↓ | n/↑ | ↓ | ↑ |
| IGFBP-3 | ↓ | n/↓ | ↓ | n | n/↑ | ↓ | ↑ |
| ALS | n/↓ | n/↓ | +/− | n | n/r | ↓ | ↑ |
| GH | ↑ | n/↑ | ↑ | n/↑ | n/↑ | ↑ | ↑ |
| GHBP deficiency | +/− | – | – | – | – | – | – |
The following symbols apply: +, positive; –, negative; +/−, predominantly positive; −/+, predominantly negative; *, ∼50%; ↑, increased; ↓, decreased.
Abbreviations: n, normal; n/a, not applicable; n/r, not reported.