A Japanese patient with congenital central hypothyroidism caused by a novel IGSF1 mutation.

BACKGROUND: IGSF1 abnormality causes diverse symptoms, including congenital central hypothyroidism (CCH), prolactin hyposecretion, testicular enlargement and delayed puberty.

CASE PRESENTATION: Here, we report a case of a male patient who visited our hospital with a chief complaint of abdominal pain and short stature, in whom we identified a novel IGSF1 mutation. He was closely examined because of chronic constipation since infancy, persistent abdominal pain at 14 years of age and marked short stature (-4.7 standard deviation [SD] for normal Japanese boys). He was diagnosed with CCH. Decreased prolactin (PRL) secretion was also observed. IGSF1 analysis revealed a novel mutation at the splicing donor site (c.2065+1G>A) in intron 11. In silico analysis predicted this mutation to be a non-functional splice donor site. After thyroid hormone replacement, his thyroid function, constipation and growth rate improved.

CONCLUSIONS: This is the first report of a patient in whom constipation and short stature led to a diagnosis of CCH with a novel IGSF1 mutation.