John H Livingston1, Josephine Mayer2, Emma Jenkinson2, Paul Kasher2, Stavros Stivaros3, Andrea Berger4, Duccio M Cordelli5, Patrick Ferreira6, Rosalind Jefferson7, Georg Kutschke8, Staffan Lundberg9, Katrin Ounap10, Prab Prabhakar11, Calvin Soh12, Helen Stewart13, Jon Stone14, Marjo S van der Knaap15, Hilda van Esch16, Christine van Mol16, Emma Wakeling17, Andrea Whitney18, Gillian I Rice1, Yanick J Crow1. 1. Department of Paediatric Neurology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom. 2. Department of Genetic Medicine, University of Manchester, Manchester Academic Health Science Centre, Central Manchester Foundation Trust University Hospitals, Manchester, United Kingdom. 3. Imaging, Genomics and Proteomics Research Group, University of Manchester, Manchester, United Kingdom. 4. Department of Pediatric Neurology, Children's Hospital, Harlaching, Munich and University of Mainz, Germany. 5. Child Neuropsychiatry Unit, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy. 6. Division of Medical Genetics, Alberta Children's Hospital, Calgary, Canada. 7. Department of Paediatrics, Royal Berkshire Hospital, Reading, United Kingdom. 8. Department of Pediatrics and Neonatology, Universitätsklinikum des Saarlandes, Homburg, Germany. 9. Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden. 10. Department of Genetics, Tartu University Hospital, Tartu, Estonia. 11. Department of Neurology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom. 12. Department of Neuroradiology, Salford Royal NHS Foundation Trust, Salford, United Kingdom. 13. Department of Clinical Genetics, Oxford Radcliffe Hospitals NHS Trust, Oxford, United Kingdom. 14. Department of Clinical Neurosciences, Western General Hospital, Edinburgh, United Kingdom. 15. Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands. 16. Center for Human Genetics, University Hospitals Leuven, KU Leuven, Leuven, Belgium. 17. North West Thames Regional Genetics Service, North West London Hospitals NHS Trust, Harrow, United Kingdom. 18. Department of Paediatric Neurology, Southampton General Hospital, Southampton, United Kingdom.
Abstract
OBJECTIVE: With the identification of mutations in the conserved telomere maintenance component 1 (CTC1) gene as the cause of Coats plus (CP) disease, it has become evident that leukoencephalopathy with calcifications and cysts (LCC) is a distinct genetic entity. PATIENTS AND METHODS: A total of 15 patients with LCC were identified from our database of patients with intracranial calcification. The clinical and radiological features are described. RESULTS: The median age (range) at presentation was 10 months (range, 2 days-54 years). Of the 15 patients, 9 presented with epileptic seizures, 5 with motor abnormalities, and 1 with developmental delay. Motor abnormalities developed in 14 patients and cognitive problems in 13 patients. Dense calcification occurred in the basal ganglia, thalami, dentate nucleus, brain stem, deep gyri, deep white matter, and in a pericystic distribution. Diffuse leukoencephalopathy was present in all patients, and it was usually symmetrical involving periventricular, deep, and sometimes subcortical, regions. Cysts developed in the basal ganglia, thalamus, deep white matter, cerebellum, or brain stem. In unaffected areas, normal myelination was present. No patient demonstrated cerebral atrophy. CONCLUSION: LCC shares the neuroradiological features of CP. However, LCC is a purely neurological disorder distinguished genetically by the absence of mutations in CTC1. The molecular cause(s) of LCC has (have) not yet been determined. Georg Thieme Verlag KG Stuttgart · New York.
OBJECTIVE: With the identification of mutations in the conserved telomere maintenance component 1 (CTC1) gene as the cause of Coats plus (CP) disease, it has become evident that leukoencephalopathy with calcifications and cysts (LCC) is a distinct genetic entity. PATIENTS AND METHODS: A total of 15 patients with LCC were identified from our database of patients with intracranial calcification. The clinical and radiological features are described. RESULTS: The median age (range) at presentation was 10 months (range, 2 days-54 years). Of the 15 patients, 9 presented with epileptic seizures, 5 with motor abnormalities, and 1 with developmental delay. Motor abnormalities developed in 14 patients and cognitive problems in 13 patients. Dense calcification occurred in the basal ganglia, thalami, dentate nucleus, brain stem, deep gyri, deep white matter, and in a pericystic distribution. Diffuse leukoencephalopathy was present in all patients, and it was usually symmetrical involving periventricular, deep, and sometimes subcortical, regions. Cysts developed in the basal ganglia, thalamus, deep white matter, cerebellum, or brain stem. In unaffected areas, normal myelination was present. No patient demonstrated cerebral atrophy. CONCLUSION: LCC shares the neuroradiological features of CP. However, LCC is a purely neurological disorder distinguished genetically by the absence of mutations in CTC1. The molecular cause(s) of LCC has (have) not yet been determined. Georg Thieme Verlag KG Stuttgart · New York.
Authors: Alex J Fay; Allison A King; Joshua S Shimony; Yanick J Crow; Jan E Brunstrom-Hernandez Journal: Pediatr Neurol Date: 2017-03-23 Impact factor: 3.372
Authors: Emma M Jenkinson; Mathieu P Rodero; Paul R Kasher; Carolina Uggenti; Anthony Oojageer; Laurence C Goosey; Yoann Rose; Christopher J Kershaw; Jill E Urquhart; Simon G Williams; Sanjeev S Bhaskar; James O'Sullivan; Gabriela M Baerlocher; Monika Haubitz; Geraldine Aubert; Kristin W Barañano; Angela J Barnicoat; Roberta Battini; Andrea Berger; Edward M Blair; Janice E Brunstrom-Hernandez; Johannes A Buckard; David M Cassiman; Rosaline Caumes; Duccio M Cordelli; Liesbeth M De Waele; Alexander J Fay; Patrick Ferreira; Nicholas A Fletcher; Alan E Fryer; Himanshu Goel; Cheryl A Hemingway; Marco Henneke; Imelda Hughes; Rosalind J Jefferson; Ram Kumar; Lieven Lagae; Pierre G Landrieu; Charles M Lourenço; Timothy J Malpas; Sarju G Mehta; Imke Metz; Sakkubai Naidu; Katrin Õunap; Axel Panzer; Prab Prabhakar; Gerardine Quaghebeur; Raphael Schiffmann; Elliott H Sherr; Kanaga R Sinnathuray; Calvin Soh; Helen S Stewart; John Stone; Hilde Van Esch; Christine E G Van Mol; Adeline Vanderver; Emma L Wakeling; Andrea Whitney; Graham D Pavitt; Sam Griffiths-Jones; Gillian I Rice; Patrick Revy; Marjo S van der Knaap; John H Livingston; Raymond T O'Keefe; Yanick J Crow Journal: Nat Genet Date: 2016-08-29 Impact factor: 38.330