Abstract Causal variants in the IGF 1 receptor (IGF1R) gene are associated with variable degrees of growth and neurodevelopmental impairment. While heterozygous variants often manifest as less severe phenotypes, homozygous loss-of-function mutations are widely regarded as incompatible with life. Biallelic hypomorphic variants are exceptionally rare and their clinical spectrum remains poorly defined. We report the case of a girl born at term after severe symmetric fetal growth restriction (FGR), identified prenatally through trio whole-exome sequencing as carrying compound heterozygous IGF1R variants—c.155GC (p.Cys52Ser) and c.3476AG (p.Asp1159Gly). Postnatally, she exhibited microcephaly, dysmorphic features, and marked growth failure. Growth hormone therapy was initiated at 13 months of age, leading to gradual and sustained improvement in head circumference, linear growth, and psychomotor development. We report a rare case of a prenatal diagnosis of compound heterozygous IGF1R variants with early GH treatment. The case broadens current knowledge on IGF1R-related disorders, shows that survival is possible in compound heterozygous states, and suggests a potential benefit of early GH therapy.
Pinto et al. (Sat,) studied this question.