A novel variant of THRβ and its 4-year clinical course in a Korean boy with resistance to thyroid hormone

Thyroid hormone resistance (RTH) is characterized by a decreased sensitivity of target tissues to thyroid hormones due to a defect in the THRα- and THRβ-encoded thyroid hormone receptors (THRs). The clinical manifestations range from no symptoms to simple goiter and hypo- or hyperthyroidism, depending on the receptor subtype distribution in the tissues. Here, we report the case of a thyroid hormone-resistant 12-month-old boy carrying a novel THRβ variant who was initially diagnosed with congenital hypothyroidism. An extensive evaluation revealed increased free T4 level and inappropriately increased thyroid-stimulating hormone (TSH) level; a normal lipid profile, sex hormone-binding globulin, and free alpha subunit of TSH; exaggerated TSH response to THR; and no radiological evidence of pituitary adenoma. A targeted next-generation sequencing panel identified a heterozygote c.993T>G (p.Asn331Lys) mutation in the THRβ gene. During the first year of life, a higher dose of levothyroxine was administered to the patient due to uncompensated RTH. Levothyroxine treatment was continued after 3 years to maintain TSH level <5 mIU/mL, but the observed weight gain was poor, height increase was insufficient, and bone development was delayed. However, neither hyperactivity nor developmental delay was observed. Patients with RTH exhibit various clinical features. Due to its heterogeneous nature, genetic test for accurate diagnosis is important to provide proper management.

A Case of Incontinentia Pigmenti with Developmental Delay / 대한소아신경학회지

Incontinentia pigmenti(IP), so called Bloch-Sulzberger syndrome is a rare hereditary neurocutaneous syndrome and was described first by Bardach in l925. This disorder is known as a systemic disease caused by a defect at the developmental stage of organs originated from ectoderm or mesoderm. Incontinentia pigmenti is presented by characteristic linear hyperpigmented skin lesions, often associated with central nervous system involvement, dysplasia in the dental system, and ocular abnormalities. This disorder occurs almost in female infants, usually lethal in males, inherited as X-linked dominantly. Thirty percent of the patients suffer from central nervous system complications such as mental retardation, encephalopathy, delayed development, seizure, spastic paralysis and microcephaly. We report a case of a 12 month-old female with incontinentia pigmenti who was hospitalized with linear hyperpigmented skin lesions and delayed development.