Laron Dwarfism (GHR)
Pathogenic variants in the gene GHR causes Laron dwarfism, an autosomal recessive disorder characterized by normal or high serum growth hormone and low serum insulin-like growth factor-1 (IGF1) levels which fail to rise after exogenous GH administration. The age of onset is infancy. This disorder is characterized by short stature, reduced muscle strength and endurance, low blood sugar levels in infancy, delayed puberty, thin and fragile hair, and dental abnormalities. Many affected individuals have a distinctive facial appearance, including a protruding forehead, a sunken bridge of the nose, and a blue tint to the whites of the eyes. Life expectancy of affected individuals is normal. This disorder occurs at a greater frequency in the Semitic or Mediterranean populations and a large group from the area of southern Ecuador. Some individuals with a heterozygous pathogenic variant in GHR may be affected with partial growth hormone insensitivity, which is inherited in an autosomal dominant manner and is characterized by partial resistance to growth hormone in the presence of normal or high levels of circulating growth hormone. The age of onset is childhood. This disorder is characterized by short stature, delayed onset of puberty, low blood sugar in infancy and early childhood, and obesity in adulthood. Life expectancy of affected individuals is normal. No clear genotype-phenotype correlation has been reported.
For information about carrier frequency and residual risk, please see the residual risk table.