Male patients with the X-linked IGSF1 deficiency syndrome are characterized by central hypothyroidism, delayed pubertal testosterone rise, adult macroorchidism, variable prolactin deficiency and occasionally transient partial growth hormone deficiency. Thyroid hormone plays a vital role in brain development and functioning, and while most patients receive adequate replacement therapy starting shortly after birth, it is unknown whether this syndrome is accompanied by long-term impaired cognitive functioning. We therefore assessed cognitive functioning in male patients with IGSF1 deficiency.Methods
Fifteen adult male patients with IGSF1 deficiency participated in neuropsychological assessment of executive functioning and memory, and completed validated questionnaires on health-related quality of life (HRQoL), mood and fatigue. Results were compared to data from previous studies by our department: 54 healthy controls (76 for the attention task) for the test battery and 191 healthy controls for the questionnaires.Results
All patients had central hypothyroidism, and twelve were treated with levothyroxine. Patients performed worse than controls in tasks that required attentional control (Trail Making Test, Letter-Digit Substitution Test, and Sustained Attention to Response Task) (all P < 0·001). Memory was unaffected. In addition, patients reported more mental fatigue and reduction of activity (Multidimensional Fatigue Inventory) (both P < 0·01), while HRQoL and mood reports were not different from controls. Age at the start of replacement therapy and current thyroxine levels were not related to outcome.Conclusions
Adult male patients with IGSF1 deficiency exhibit mild deficits in attentional control on formal testing. This finding was not related to the age at start of replacement therapy, or current levothyroxine treatment.