PMC6300407_01
Clinical and biochemical features of the patient with a TBL1X defect. (A) Pedigree of members of the family showing patient born of twin pregnancy from nonconsanguineous parents. Thyroid hormone profile and glycosylated hemoglobin were used to evaluate hypothyroidism and diabetes, respectively, in all members of the family. Italics represent values above normal ranges. (B) Thyrotropin response of the index patient (6 y of age without levothyroxine treatment) at the TRH test during 180 min. TSH and prolactin (Prl) values are represented in the graph through time during the 3 h of the test. Fold increase of TSH was calculated by dividing the TSH value at each time (0, 15, 30, 60, 120, or 180 min) by the TSH level at the beginning of the test (0 min). FT4 increase 3 h after TRH administration was calculated as reported, as an indirect measure of TSH bioactivity, and was normal. Underlining represents values below normal ranges. (C) Thyroid ultrasound at 6 y and 9 mo of age, representing three-dimensional measures of each lobule, showed mild hypoplasia of the gland. (D) Brain MRI in the index case at 6.5 y of age showing normal pituitary morphology and size (white asterisk) but a downward herniation of cerebellar tonsils protruding through the foramen magnum (CMI), which compresses the spinal cord (white arrows). (E) Hearing loss per frequency in the right and left ear of the index patient is represented in left and right panels, respectively. %FT4 Incr, percentage of FT4 increase; N.R., normal range; wt, wild-type.
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F1
The patient is a 10-year-old male of Spanish descent, born to nonconsanguineous parents in a twin pregnancy derived from in vitro fertilization of own parental sperm and oocytes (Fig. 1A). His mother and twin sister showed an unremarkable phenotype (Fig. 1A). A 180-minute TRH test was performed to investigate the origin of his hypothyroidism, showing reduced TSH stimulation (low TSH secretion capacity) and full recovery of the basal TSH level at the end of the test (Fig. 1B), suggesting a pituitary defect. Neck ultrasounds showed mild hypoplasia of the thyroid gland with 1.84 mL volume (p50: 3.05 mL) (Fig. 1C). Brain MRI showed normal pituitary size and shape, but a CMI was identified, consisting of the aberrant displacement of the cerebellar tonsils into the foramen magnum (Fig. 1D). ADHD was indicated, but he did not receive therapy due to parental decision. At 10 years of age, a pure-tone audiometry was performed, which identified poor hearing thresholds in the air conduction at high frequencies compared with the age-specific reference interval (Fig. 1E).