A Novel Pathogenic IGSF1 Variant in a Patient with GH and TSH Deficiency Diagnosed by High IGF-I Values at Transition to Adult Care
Aslı Derya Kardelen1, Esin Karakılıç Özturan1, Şükran Poyrazoğlu1, Firdevs Baş1, Serdar Ceylaner2, Sjoerd D. Joustra3, Jan M. Wit3, Feyza Darendeliler11İstanbul University, İstanbul Faculty of Medicine, Department of Pediatric Endocrinology, İstanbul, Turkey2Intergen Genetic Research Center, Ankara, Turkey
3Willem-Alexander Children’s Hospital; Leiden University Medical Center, Department of Pediatrics, Division of Pediatric Endocrinology, Leiden, Netherlands
IGSF1 deficiency is a rare X-linked condition characterized by central hypothyroidism and a wide variety of other clinical features with variable prevalence, including a delayed pubertal testosterone rise and growth spurt in the context of normal or accelerated testicular growth, and adult macroorchidism with relatively low serum testosterone concentrations. Other features include increased waist circumference, attention deficit, prolactin deficiency and transient partial growth hormone (GH) deficiency in childhood, contrasting with an increased GH secretion in adulthood. Patients with this disorder are not detected shortly after birth if neonatal screening programs are based on thyroid-stimulating hormone (TSH) concentrations. A 13.2-year-old male patient was referred to pediatric endocrinology for evaluation of short stature. He was born large for gestational age into a nonconsanguineous family. During work-up for short stature, deficiencies of TSH, prolactin and GH were detected, leading to treatment with levothyroxine and GH. At 16.9 years, GH treatment was stopped and during transition to adult care, his insulin-like growth factor 1 level was above the normal range. This prompted an analysis of IGSF1, in which a novel hemizygous variant causing a stop codon at c.3559C>T (p.Q1187*) was found, confirming the diagnosis of IGSF1 deficiency syndrome. In this report, we describe his clinical and hormonal characteristics at presentation and during long-term follow-up.
Keywords: IGSF1, central hypothyroidism, short stature, large for gestational age, growth hormone deficiency, prolactin eficiencyManuscript Language: English
