Table 3.
Genetic Diagnosis to Detect the Individual Molecular Basis of CH
| Thyroid Morphology, as Assessed by Ultrasonography and/or Scintigraphy | Family History |
||
|---|---|---|---|
| Consanguinity or Siblings/Cousins With CH | Parents With CH | ||
| Isolated CH | Normally located thyroid with normal perchlorate discharge test | TSH-R (if hypoplasia), TG (if goiter, low TG level) | PAX8 |
| Normally located thyroid with abnormal perchlorate discharge test (ie, iodide organification defects) | TPO, DUOX2/DUOXA2 +/− TG | ||
| Normally located thyroid on ultrasonography, with no iodide uptake on scintigraphy | SCL5A5/NIS, TSH-R (if hypoplasia) | ||
| Syndromic CH | |||
| Deafness | Normally located thyroid | SCL26A4/PDS | |
| Short stature, obesity, hypocalcemia | Normally located thyroid | GNAS | |
| Cleft palate, “spiky” hair | Athyreosis (hypoplasia) | FOXE1 (no mutations described in patients with ectopic or normally sized and sited thyroid gland to date) | |
| Kidney agenesis or any malformation of the genitourinary tract | Athyreosis, ectopic thyroid gland, normally located thyroid +/− hypoplasia | PAX8 | PAX8 |
| Choreoathetosis or neurological disease | Normally located thyroid, hypoplasia (athyreosis) | NKX2–1 (no mutations described in ectopic cases so far) | NKX2–1 |
| Lung disorders (surfactant deficiency syndrome at term, interstitial lung disease) | Normally located thyroid, hypoplasia (athyreosis) | NKX2–1 (no mutations described in ectopic cases so far) | NKX2–1 |
| Cardiac defects | Ectopy (athyreosis) | NKX2–5 | NKX2–5 |