An Xp; Yq translocation causing a novel contiguous gene syndrome in brothers with generalized epilepsy, ichthyosis, and attention deficits.
OBJECTIVE
We describe two brothers with generalized epilepsy, attention deficits, congenital ichthyosis, and Leri-Weill dyschondrosteosis who harbor an unusual Xp; Yq translocation chromosome, resulting in a novel contiguous gene syndrome because of deletion of genes from the distal short arm of the X chromosome.


METHODS
Physical examination, neuropsychologic testing, EEG, and neuroimaging studies were performed. Because of their unusual phenotype, karyotyping, fluorescence in situ hybridization, and further molecular analyses were carried out to refine the break points of the underlying unbalanced sex chromosome rearrangement.


RESULTS
The subjects had generalized epilepsy, X-linked ichthyosis, Madelung deformities, mesomelia, normal intelligence, and attention deficits. The brothers' karyotype was unbalanced; they inherited a maternal derivative X chromosome. Deleted distal Xp genes included short-stature homeobox on the X chromosome (SHOX), aryl sulfatase E (ARSE), variably charged X-chromosome mRNA gene A (VCX-A), and steroid sulfatase (STS). The final karyotype was 46,Y,der(X)t(X; Y)(p22.3; q11.2).ish der(X) (DXZ1+, KAL+, STS-, SHOX-) mat.


CONCLUSIONS
Loss of distal contiguous Xp genes resulted in a syndrome comprising bony deformities, ichthyosis, attention problems, and generalized epilepsy. Candidate epilepsy genes within the deleted segment, such as ASMT, a gene involved in the final synthesis of melatonin, are discussed. Cytogenetic analyses should be included in the clinical evaluation of patients with generalized epilepsy and complex phenotypes.
Doherty
Michael J
MJ
Swedish Epilepsy Center, University of Washington, Seattle, Washington, U.S.A. Michael.Doherty@Swedish.org
Glass
Ian A
IA
Bennett
Craig L
CL
Cotter
Phil D
PD
Watson
Nate F
NF
Mitchell
Anna L
AL
Bird
Tom D
TD
Farrell
Don F
DF
D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D019457:Chromosome Breakage; D002872:Chromosome Deletion; D041321:Chromosomes, Human, X; D041322:Chromosomes, Human, Y; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics; D004392:Dwarfism / Q000175:diagnosis / Q000235:genetics; D004829:Epilepsy, Generalized / Q000175:diagnosis / Q000235:genetics*; D006580:Genetic Carrier Screening; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D016114:Ichthyosis, X-Linked / Q000175:diagnosis / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012729:Sex Chromosome Aberrations; D035781:Siblings; D013577:Syndrome; D014178:Translocation, Genetic
D005819:Genetic Markers; D009687:Nuclear Proteins; C404411:VCX protein, human