title: Mild deficits in attentional control in patients with the IGSF1 deficiency syndrome.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.|Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: S D
authors.initials: SD
authors.lastname: Joustra
authors.affiliation: Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: C D
authors.initials: CD
authors.lastname: Andela
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: Oostdijk
authors.affiliation: Department of Pediatric Endocrinology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: A S P
authors.initials: AS
authors.lastname: van Trotsenburg
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Fliers
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: Wit
authors.affiliation: Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Pereira
authors.affiliation: Department of Psychology, Section Health, Medical and Neuropsychology, Leiden University, Leiden, The Netherlands.|Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: H A M
authors.initials: HA
authors.lastname: Middelkoop
authors.affiliation: Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: N R
authors.initials: NR
authors.lastname: Biermasz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001288:Attention; D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology*; D016022:Case-Control Studies; D056344:Executive Function; D006801:Humans; D007037:Hypothyroidism / Q000150:complications / Q000188:drug therapy*; D007136:Immunoglobulins / Q000172:deficiency*; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency*; D008568:Memory; D008875:Middle Aged; D009426:Netherlands; D009483:Neuropsychological Tests; D011788:Quality of Life; D011795:Surveys and Questionnaires; D013974:Thyroxine / Q000627:therapeutic use; D055815:Young Adult
chemical_list: C112314:IGSF1 protein, human; D007136:Immunoglobulins; D008565:Membrane Proteins; D013974:Thyroxine