Zeitschrift für genetische Syndrome und Gentherapie
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Abstrakt

Genetically Determined Central Hypothyroidism

Antonis Voutetakis, Nikolaos Settas and Catherine Dacou-Voutetakis

Central, secondary or low TSH hypothyroidism can be congenital or acquired. Congenital Central hypothyroidism (CH-C), either isolated or (unlike primary hypothyroidism) combined with deficiency of other pituitary hormones, is usually caused by mutations in genes related either to TSH synthesis or pituitary ontogenesis. The prevalence of CH-C is higher than previously considered, ranging from 1:16000 to 1:20000 live births. Isolated CH-C is most frequently caused by mutations in the TSΗβ-subunit and in rare cases by TRHR gene mutations. Either one of these mutations are inherited as a recessive trait. In patients with multiple pituitary hormone deficiency, molecular defects have been detected in the following genes: IGSF1, PROP1, POU1F1, LHX3, LHX4, HESX1, SHH, TGIF, GLI2. The resulting phenotype varies and the mode of inheritance could be autosomal dominant, autosomal recessive or X-linked, depending on the specific gene involved. In patients with CH-C, the timely identification of the underlying genetic defect is crucial because it leads to early and appropriate management that improves prognosis and determines genetic counseling.