ESPE Abstracts

Introduction: The IGSF1 gene deficiency syndrome (IDS) is an X-linked disorder involving hormonal disfunctions. We report a case of Central Hypothyroidism (CH) due to a Xq26.1q26.2 microdeletion including the IGSF1 gene.

Case: this boy was referred to our clinic for thyroid dysfunction. He was born at term by caesarean section due to maternal uterine myoma. Pregnancy was normal, parents were non consanguineous. Birth weight was 3412 gr (0.3 SDS), length was 51 cm (0.63 SDS) head circumference was 36 cm (1.42 SDS). Maternal family history was significant for intellectual disability, mother had hypoprolactinaemia and was unable to brestfeed. Due to speech disorder and stereotypies, neuropsychiatric evaluations were performed and autism was diagnosed. Electroencephalogram, brain MRI and metabolic investigations were normal. Ophthalmological evaluation showed possible astigmatism. Mild hearing loss was also found. Genetic investigations included FMR1 molecular analysis (negative) and CGH-array, that showed a q26.1q26.2 microdeletion inherited from the mother, including the IGSF1 gene. At the first evaluation at the age of 3 years and 6 months height was 111.7 cm (2.86 SDS), within the family range, weight was 24.4 kg (3.57 SDS), head circumference was 54.5 cm (3.39 SDS). Testicular volume was 3 ml. Phenotype was normal, bone age was 6 months delayed according to Greulich & Pyle atlas. Blood exams showed low levels of FT4 associated with normal TSH according to laboratory reference ranges. TRH test was performed revealing normal values of TSH after stimulation and low FT4. Blood levels of other hormones were normal and thyroid ultrasound showed a normal thyroid gland. As low FT4 was persistent with increasingly lower FT3 levels in addition, Levothyroxine was started (25 mg/die) and progressively increased according with blood FT4 values and auxological parameters. TSH levels gradually decreased during months becoming not measurable (< 0,01 microU/ml) at the age of 5 years and 8 months. Growth rate persisted normal. Relative macroorchidism was present, hormonal assessment was prepubertal.

Discussion: The most frequent endocrine condition associated with IDS is CH, that presented gradually in our patient. IDS may also involve delayed testosterone rise in puberty, macroorchidism in adult age, variable prolactin deficiency, occasional partial GH deficiency and overweight habitus. Levothyroxine replacement therapy is required as well as biochemical and auxological follow-up, to identify potential onset of hormonal defects and promptly start treatment. Due to X-linked inheritance, genetic evaluation of family members should be considered.