Characterized by a very short stature, facial changes, and obesity, Laron syndrome is an autosomal recessive genetic disorder in which insensitivity to growth hormone by tissues is the main pathological entity. Mutations in the growth hormone gene have shown to be responsible for the disorder, but the diagnosis can be made only after a thorough clinical and laboratory workup.
The clinical presentation of patients suffering from Laron syndrome, occurring due to growth hormone (GH) insensitivity, is diverse, but the two most important features are dwarfism and obesity  . The majority of patients exhibit short stature from birth, and a progressive deficit in growth and development throughout childhood leads to finite body heights between 4 and 10 height standard deviations (SDs) below the average for appropriate age . In addition, very small hands and feet (known as acromicria) are observed, as well as short limbs compared to the size of the trunk . Obesity is progressive, despite the fact that the caloric intake is normal or even reduced, and occurs on the grounds of reduced muscle and bone content . It often predisposes patients to sleep apnea, skin wrinkling and joint pain as a result of poor muscle strength, which may be quite debilitating   . Genital and hormonal abnormalities, such as hypogonadism and underdevelopment of the genital organs (or hypogenitalism, manifesting as micropenis, small testes, and reduced ovarian size, respectively) are frequent findings in children suffering from this genetic disorder. Moreover, puberty is often delayed, and secondary sexual characteristics typically develop later in adolescence   . Facial changes, including protrusion of the forehead, a saddle nose, hypoplasia of the mandible and other facial bones, thin hair and delayed teething are common features as well  . Delayed nail growth and blue sclerae may also be present .
The diagnosis of Laron syndrome can be difficult to attain without a thorough patient history and a meticulous physical examination. The autosomal recessive nature of the disorder may be the reason why it is identified almost exclusively in families with consanguineous marriages, and the majority of patients are of Middle-Eastern or Mediterranean origin  . For this reason, the presence of similar symptoms and signs in among close relatives or siblings may be a valuable clue toward the diagnosis, whereas a complete physical examination provides sufficient clinical criteria to assume impaired growth hormone activity. Basic laboratory workup should include estimation of glucose levels, as many patients suffer from hypoglycemia, the later development of diabetes mellitus and insulin intolerance, together with serum alkaline phosphatase (ALP), creatinine, a full lipid profile, and hormonal assessment . Paradoxically, growth hormone (GH) levels are normal or markedly elevated when exogenous stimulation is performed, but the values of insulin-like growth factor 1 (IGF-1) are quite low, which serves as one of the key regulators of GH activity . Low IGF-1 levels are thought to explain the mild pancytopenia that is observed in patients, due to its potential role in erythropoiesis . Imaging studies, such as plain radiography and computed tomography (CT), could be used to assess skeletal and soft-tissue changes, respectively. Even though the diagnosis is often made based on clinical and laboratory criteria  , genetic studies should be carried out, if possible, in order to confirm GH insensitivity .