Table 1.
Candidate genes in inheritable forms of central hypothyroidism (CeH) and related phenotypes
| Genes (OMIM*) | Inheritance and phenotype (OMIM#) |
|---|---|
| TSHβ (188540) | Recessively inherited isolated CeH of neonatal onset with low TSH, high α-GSU and normal PRL concentrations, pituitary hyperplasia reversible on L-T4 replacement (275100) |
| TRHR (188545) | Recessively inherited CeH with normal TSH and low PRL concentrations, blunted TSH/PRL responses to TRH, male index cases referred for growth retardation or overweight during childhood, 1 female proband referred for prolonged neonatal jaundice; no lactation defect in affected women |
| TBL1X (300196) | X-linked mild isolated CeH, normal TSH concentrations, impaired hearing |
| IGSF1 (300137) | X-linked CeH (affecting males and females with skewed X chromosome inactivation), associated with low PRL, variable GH deficiency, metabolic syndrome, and postpubertal macroorchidism (+2.0 SDS) (300888) |
| POU1F1 (173110) | Dominantly or recessively inherited CeH of variable age of onset, combined with GH and PRL defects, prominent forehead, midface hypoplasia, depressed nose (613038) |
| PROP1 (601538) | Recessively inherited CeH with variable age of onset, combined with GH, PRL, LH/FSH defects, and delayed ACTH deficiency, small to large pituitary volume (262600) |
| HESX1 (601802) | Dominantly or recessively inherited hypopituitarism associated with septo-optic dysplasia (182230) |
| SOX3 (313430) | X-linked hypopituitarism, anterior pituitary hypoplasia with ectopic posterior pituitary, persistent cranio-pharyngeal canal, and learning difficulties (312000) |
| SOX2 (184429) | Dominantly inherited variable hypopituitarism, pituitary hypoplasia, microphthalmia, variable learning difficulties (206990) |
| OTX2 (600037) | Dominantly inherited hypopituitarism, anterior pituitary hypoplasia with ectopic posterior pituitary, and ocular defects (ano/microphthalmia/retinal dystrophy) (610125) |
| LHX3 (600577) | Recessively inherited hypopituitarism with inconstant ACTH defect, small to large pituitary, short and rigid cervical spine, and variable hearing defect (221750) |
| LHX4 (602146) | Dominant or recessively inherited variable hypopituitarism, anterior pituitary hypoplasia with ectopic posterior pituitary, Arnold-Chari syndrome, corpus callosum hypoplasia (262700) |
| NFKB2 (164012) | Dominantly inherited DAVID syndrome (variable immune deficiency and ACTH defect) with variable GH and TSH deficiency (615577) |
| CHD7 (608892) | Dominantly inherited CHARGE syndrome (coloboma, heart anomaly, choanal atresia, retardation, genital, and ear anomalies) with ectopic posterior pituitary and variable LH/FSH, TSH, and GH defects (214800) |
| FGFR1 (136350) | Dominantly inherited Kallmann syndrome (central hypogonadism and anosmia), variable associations with defects of other pituitary hormones including TSH, septo-optic dysplasia, and ectopic posterior pituitary |
| FGF8 (600483) | Recessively inherited Kallmann syndrome, variable associations with defects of other pituitary hormones including TSH, holoprosencephaly, and corpus callosum agenesia |
| FOXA2 (600288) | Dominant hypopituitarism with craniofacial and endoderm-derived organ abnormalities, and hyperinsulinism |
| PROKR2 (607123) | Variable hypopituitarism associated with septo-optic dysplasia or pituitary stalk interruption, variable inheritance |
| LEPR (601007) | Recessively inherited hyperphagia and obesity, combined with central hypogonadism and hypothyroidism (614963) |