Laron syndrome
Laron syndrome (LS), also known as growth hormone insensitivity or growth hormone receptor deficiency (GHRD), is an autosomal recessive disorder characterized by a lack of insulin-like growth factor 1 (IGF-1; somatomedin-C) production in response to growth hormone (GH; hGH; somatotropin). It is usually caused by inherited growth hormone receptor (GHR) mutations.
| Laron syndrome | |
|---|---|
| Other names | genetic pituitary dwarfism (1966), Laron dwarfism (1973), Laron-type dwarfism (1984), growth hormone insensitivity (1994), hereditary somatomedin deficiency, growth hormone receptor deficiency (GHRD)(1999) |
| Growth hormone | |
| Specialty | Endocrinology, Medical Genetics, Pediatrics |
| Symptoms | Short stature, truncal obesity, facial dysmorphism |
| Usual onset | Present at birth |
| Duration | Lifelong |
| Causes | Autosomal recessive growth hormone receptor gene mutation (chromosome 5) |
| Risk factors | Hypoglycemia, seizures, reduced intellectual capacity, osteopenia |
| Differential diagnosis | STAT5b, IGF1 gene mutation, ALS deficiency, IGF-1 receptor mutation, familial short stature, malnutrition, hepatic disease, congenital growth delay, hypopituitarism |
| Treatment | IGF-1, Mecasermin |
| Frequency | 1–9 / 1,000,000 (approximately 250 known cases worldwide) |
Affected individuals classically present with short stature between −4 and −10 standard deviations below median height, obesity, craniofacial abnormalities, micropenis, low blood sugar, and low serum IGF-1 despite elevated basal serum GH.
LS is a very rare condition with a total of 250 known individuals worldwide. The genetic origins of these individuals have been traced back to Mediterranean, South Asian, and Semitic ancestors, with the latter group comprising the majority of cases. Molecular genetic testing for growth hormone receptor gene mutations confirms the diagnosis of LS, but clinical evaluation may include laboratory analysis of basal GH, IGF-1 and IGFBP levels, GH stimulation testing, and/or GH trial therapy. Treatment options include recombinant IGF-1 (Mecasermin).
Evidence has suggested that people with Laron syndrome have a reduced risk of developing cancer and diabetes mellitus type II, with a significantly reduced incidence and delayed age of onset of these diseases compared to their unaffected relatives. The molecular mechanisms of increased longevity and protection from age-related disease among people with LS is an area of active investigation.