Neurology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Data Supplement
Right arrow Correspondence:
Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Correspondence are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bosley, T. M.
Right arrow Articles by Engle, E. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bosley, T. M.
Right arrow Articles by Engle, E. C.
Related Collections
Right arrow MRI
Right arrow Ocular motility
Right arrow All Neuropsychology/Behavior
Right arrow Audition
Right arrow All Psychiatric disorders
Right arrow All Genetics
Right arrow Genetic linkage
NEUROLOGY 2007;69:1245-1253
© 2007 American Academy of Neurology

Clinical characterization of the HOXA1 syndrome BSAS variant

T. M. Bosley, MD, M. A. Salih, MD, I. A. Alorainy, MD, D. T. Oystreck, OC(C), M. Nester, PhD, K. K. Abu-Amero, PhD, M. A. Tischfield, BA and E. C. Engle, MD

From the Neuro-ophthalmology Division (T.M.B., D.T.O.), King Khaled Eye Specialist Hospital; Division of Pediatric Neurology (M.A.S.) and Department of Radiology (I.A.A.), King Khalid University Hospital, King Saud University; Departments of Neuroscience (T.M.B., M.N.) and Genetics (K.K.A.-A.), King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia; and the Program in Genomics, Children's Hospital Boston, and Program in Neuroscience (M.A.T., E.C.E.), Harvard Medical School, Boston, MA. Dr. Bosley is now with the Neurology Division, Cooper University Hospital, Camden, NJ; and Dr. Abu-Amero is now with the Shafallah Genetics Medical Center, Doha, Qatar.

Address correspondence and reprint requests to Dr. Thomas M. Bosley, Cooper University Hospital, 3 Cooper Plaza, Suite 320, Camden, NJ 08103 Bosley-Thomas{at}cooperhealth.edu or Dr. Elizabeth C. Engle, Children's Hospital Boston, Program in Genomics, Enders 560.2, 300 Longwood Ave., Boston, MA 02115 elizabeth.engle{at}childrens.harvard.edu

Background: The Bosley-Salih-Alorainy syndrome (BSAS) variant of the congenital human HOXA1 syndrome results from autosomal recessive truncating HOXA1 mutations. We describe the currently recognized spectrum of ocular motility, inner ear malformations, cerebrovascular anomalies, and cognitive function.

Methods: We examined nine affected individuals from five consanguineous Saudi Arabian families, all of whom harbored the same I75-I76insG homozygous mutation in the HOXA1 gene. Patients underwent complete neurologic, neuro-ophthalmologic, orthoptic, and neuropsychological examinations. Six individuals had CT, and six had MRI of the head.

Results: All nine individuals had bilateral Duane retraction syndrome (DRS) type 3, but extent of abduction and adduction varied between eyes and individuals. Eight patients were deaf with the common cavity deformity of the inner ear, while one patient had normal hearing and skull base development. Six had delayed motor milestones, and two had cognitive and behavioral abnormalities meeting Diagnostic and Statistical Manual of Mental Disorders–IV criteria for autism spectrum disorder. MRI of the orbits, extraocular muscles, brainstem, and supratentorial brain appeared normal. All six appropriately studied patients had cerebrovascular malformations ranging from unilateral internal carotid artery hypoplasia to bilateral agenesis.

Conclusions: This report extends the Bosley-Salih-Alorainy syndrome phenotype and documents the clinical variability resulting from identical HOXA1 mutations within an isolated ethnic population. Similarities between this syndrome and thalidomide embryopathy suggest that the teratogenic effects of early thalidomide exposure in humans may be due to interaction with the HOX cascade.

Abbreviations: ABDS = Athabascan brainstem dysgenesis syndrome; BSAS = Bosley-Salih-Alorainy syndrome; CARS = Childhood Autism Rating Scale; CCA = common carotid artery; CCD = common cavity deformity; CN = cranial nerve; C-spine = cervical spine; DRS = Duane retraction syndrome; DSM-4 = Diagnostic and Statistical Manual of Mental Disorders; ET = esotropia; IAC = internal auditory canal; ICA = internal carotid artery; MRA = magnetic resonance angiography; NA = not available; OD = right eye; ortho = orthophoria; OS = left eye; OU = both eyes; PCom = posterior communicating artery; TOF = time-of-flight; US = ultrasound; VAB = Vineland Adaptive Behavior; WNL = within normal limits; XT = exotropia.

Supplemental data at www.neurology.org

Supported in part by NIH-RO1-EY015298 (E.C.E.).

Disclosure: The authors report no conflicts of interest.

Received January 28, 2007. Accepted in final form April 17, 2007.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 by AAN Enterprises, Inc.