PT - JOURNAL ARTICLE AU - Bhala, Sonia AU - Best, Ana F. AU - Giri, Neelam AU - Alter, Blanche P. AU - Pao, Maryland AU - Gropman, Andrea AU - Baker, Eva H. AU - Savage, Sharon A. TI - CNS manifestations in patients with telomere biology disorders AID - 10.1212/NXG.0000000000000370 DP - 2019 Dec 01 TA - Neurology Genetics PG - 370 VI - 5 IP - 6 4099 - http://ng.neurology.org/content/5/6/370.short 4100 - http://ng.neurology.org/content/5/6/370.full SO - Neurol Genet2019 Dec 01; 5 AB - Objective We systematically evaluated CNS manifestations in patients with inherited telomere biology disorders (TBDs) to better understand the clinical and biological consequences of germline aberrations in telomere biology.Methods Forty-four participants with TBDs (31 dyskeratosis congenita, 12 Hoyeraal-Hreidarsson syndrome, and 1 Revesz syndrome) enrolled in an institutional review board–approved longitudinal cohort study underwent detailed clinical assessments, brain MRI, and genetic testing. Lymphocyte telomere length Z-scores were calculated to adjust for age.Results In this cohort, 25/44 (57%) patients with a TBD had at least 1 structural brain abnormality or variant, most commonly cerebellar hypoplasia (39%). Twenty-one patients (48%) had neurodevelopmental disorder or psychomotor abnormality. Twelve had psychiatric diagnoses, including depression and/or anxiety disorders. Other findings such as hypomyelination, prominent cisterna magna, and cavum septum pellucidum were more frequent than in the general population (p < 0.001). Shorter lymphocyte telomere length was associated with an increased number of MRI findings (p = 0.02) and neurodevelopmental abnormalities (p < 0.001). Patients with autosomal recessive or X-linked TBDs had more neurologic findings than those with autosomal dominant disease.Conclusions Structural brain abnormalities and variants are common in TBDs, as are neurologic and psychiatric symptoms. The connection between neurodevelopment and telomere biology warrants future study.AD=autosomal dominant; AR=autosomal recessive; BMF=bone marrow failure; CI=confidence interval; DC=dyskeratosis congenita; DSM=Diagnostic and Statistical Manual of Mental Disorders; FISH=fluorescence in situ hybridization; IUGR=intrauterine growth restriction; OR=odds ratio; RS=Revez syndrome; TBD=telomere biology disorder; XLR=X-linked recessive