BACKGROUND AND PURPOSE: Autosomal dominant hypertension with brachydactyly features severe hypertension that causes stroke usually before the age of 50 years. We recently characterized the hypertension as featuring normal renin, aldosterone, and catecholamine responses and mapped the gene responsible to chromosome 12p. Since angiography in an affected subject had earlier shown tortuous vessels, we performed magnetic resonance tomography (MRT) angiography to look for possible neurovascular anomalies (NVA), which have been previously associated with hypertension. NVA can be caused by a looping posterior inferior cerebellar or vertebral artery. Experimental and clinical evidence suggests that NVA may cause hypertension by a compression of the ventrolateral medulla. METHODS: We performed MRT in 15 hypertensive affected (aged 14 to 57 years) and 12 normotensive nonaffected (aged 12 to 59 years) family members. We then tested for linkage between the hypertension-brachydactyly phenotypes and the presence of NVA. RESULTS: All 15 affected persons had MRT evidence for NVA. All had left-sided posterior inferior cerebellar artery or vertebral artery loops, while 6 had bilateral NVA. None of the nonaffected family members had NVA. The phenotypes were linked with an LOD score of 9.2 given a penetrance of 99%. CONCLUSIONS: Autosomal dominant hypertension and brachydactyly regularly feature NVA, which is frequently bilateral. The early age at which NVA was identified suggests that the condition is primary. We suggest that NVA may be involved in the pathogenesis of this form of hypertension and perhaps essential hypertension as well. Further studies are necessary to address the question of causation.
BACKGROUND AND PURPOSE: Autosomal dominant hypertension with brachydactyly features severe hypertension that causes stroke usually before the age of 50 years. We recently characterized the hypertension as featuring normal renin, aldosterone, and catecholamine responses and mapped the gene responsible to chromosome 12p. Since angiography in an affected subject had earlier shown tortuous vessels, we performed magnetic resonance tomography (MRT) angiography to look for possible neurovascular anomalies (NVA), which have been previously associated with hypertension. NVA can be caused by a looping posterior inferior cerebellar or vertebral artery. Experimental and clinical evidence suggests that NVA may cause hypertension by a compression of the ventrolateral medulla. METHODS: We performed MRT in 15 hypertensive affected (aged 14 to 57 years) and 12 normotensive nonaffected (aged 12 to 59 years) family members. We then tested for linkage between the hypertension-brachydactyly phenotypes and the presence of NVA. RESULTS: All 15 affected persons had MRT evidence for NVA. All had left-sided posterior inferior cerebellar artery or vertebral artery loops, while 6 had bilateral NVA. None of the nonaffected family members had NVA. The phenotypes were linked with an LOD score of 9.2 given a penetrance of 99%. CONCLUSIONS: Autosomal dominant hypertension and brachydactyly regularly feature NVA, which is frequently bilateral. The early age at which NVA was identified suggests that the condition is primary. We suggest that NVA may be involved in the pathogenesis of this form of hypertension and perhaps essential hypertension as well. Further studies are necessary to address the question of causation.
Authors: Mieczysław Litwin; Elzbieta Jurkiewicz; Katarzyna Nowak; Andrzej Kościesza; Ryszard Grenda; Katarzyna Malczyk; Iwona Kościesza Journal: Pediatr Nephrol Date: 2003-06-13 Impact factor: 3.714
Authors: Ayush Giri; Jacklyn N Hellwege; Jacob M Keaton; Jihwan Park; Chengxiang Qiu; Helen R Warren; Eric S Torstenson; Csaba P Kovesdy; Yan V Sun; Otis D Wilson; Cassianne Robinson-Cohen; Christianne L Roumie; Cecilia P Chung; Kelly A Birdwell; Scott M Damrauer; Scott L DuVall; Derek Klarin; Kelly Cho; Yu Wang; Evangelos Evangelou; Claudia P Cabrera; Louise V Wain; Rojesh Shrestha; Brian S Mautz; Elvis A Akwo; Muralidharan Sargurupremraj; Stéphanie Debette; Michael Boehnke; Laura J Scott; Jian'an Luan; Jing-Hua Zhao; Sara M Willems; Sébastien Thériault; Nabi Shah; Christopher Oldmeadow; Peter Almgren; Ruifang Li-Gao; Niek Verweij; Thibaud S Boutin; Massimo Mangino; Ioanna Ntalla; Elena Feofanova; Praveen Surendran; James P Cook; Savita Karthikeyan; Najim Lahrouchi; Chunyu Liu; Nuno Sepúlveda; Tom G Richardson; Aldi Kraja; Philippe Amouyel; Martin Farrall; Neil R Poulter; Markku Laakso; Eleftheria Zeggini; Peter Sever; Robert A Scott; Claudia Langenberg; Nicholas J Wareham; David Conen; Colin Neil Alexander Palmer; John Attia; Daniel I Chasman; Paul M Ridker; Olle Melander; Dennis Owen Mook-Kanamori; Pim van der Harst; Francesco Cucca; David Schlessinger; Caroline Hayward; Tim D Spector; Marjo-Riitta Jarvelin; Branwen J Hennig; Nicholas J Timpson; Wei-Qi Wei; Joshua C Smith; Yaomin Xu; Michael E Matheny; Edward E Siew; Cecilia Lindgren; Karl-Heinz Herzig; George Dedoussis; Joshua C Denny; Bruce M Psaty; Joanna M M Howson; Patricia B Munroe; Christopher Newton-Cheh; Mark J Caulfield; Paul Elliott; J Michael Gaziano; John Concato; Peter W F Wilson; Philip S Tsao; Digna R Velez Edwards; Katalin Susztak; Christopher J O'Donnell; Adriana M Hung; Todd L Edwards Journal: Nat Genet Date: 2018-12-21 Impact factor: 38.330