title: Expanding the neurologic phenotype of oculodentodigital dysplasia in a 4-generation Hispanic family.
abstract: We report a 4-generation Hispanic family with oculodentodigital dysplasia whose members were found to have typical phenotypic characteristics of this disorder, as well as a variable expression of neurologic manifestations in multiple generations ranging from a mild spastic gait to moderate to severe spastic tetraparesis/quadriplegia with epilepsy and an abnormal brain and spinal cord magnetic resonance imaging result. Gene testing documented a previously reported missense mutation in GJA1 (connexin 43) exon 2 (c.389T>C;p.I130T). Our evaluation not only expands the phenotypes associated with GJA1 gene mutations but also demonstrates that a great degree of variability in neurological defects can exist within a single family without evidence of genetic anticipation. A genotype-phenotype correlation between the p.I130T mutation and neurologic dysfunction appears more likely with the addition of this report's neurologic and GJA1 gene mutation findings. These findings expand the neurologic phenotype and prognosis and underscore the importance of counseling families with oculodentodigital dysplasia about the possibility of neurologic involvement.
authors.affiliation: Department of Neurology, Hospital Escuela, Tegucigalpa, Honduras.
authors.forename: Claudia
authors.initials: C
authors.lastname: Amador
authors.forename: Anne M
authors.initials: AM
authors.lastname: Mathews
authors.forename: Maria
authors.initials: M
authors.lastname: Del Carmen Montoya
authors.forename: Mary E
authors.initials: ME
authors.lastname: Laughridge
authors.forename: David B
authors.initials: DB
authors.lastname: Everman
authors.forename: Kenton R
authors.initials: KR
authors.lastname: Holden
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology; D002648:Child; D002869:Chromosome Aberrations; D018031:Connexin 43 / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000175:diagnosis / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005124:Eye Abnormalities / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D020233:Gait Disorders, Neurologic / Q000175:diagnosis / Q000235:genetics; D005799:Genes, Dominant / Q000235:genetics; D005817:Genetic Counseling; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020125:Mutation, Missense; D009460:Neurologic Examination; D010264:Paraplegia / Q000175:diagnosis / Q000235:genetics; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D011379:Prognosis; D011782:Quadriplegia / Q000175:diagnosis / Q000235:genetics; D013116:Spinal Cord / Q000473:pathology; D013576:Syndactyly / Q000175:diagnosis / Q000235:genetics*; D014071:Tooth Abnormalities / Q000175:diagnosis / Q000235:genetics*
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human