Joubert syndrome: monozygotic twins with discordant phenotypes.
We describe three sisters with Joubert syndrome, two of whom are monozygotic twins with highly discordant phenotypes. The twins were born at 34 weeks' gestation with discordant birthweights. Their anatomic, neurologic, and developmental status differs greatly: Twin B is able to walk, run, and is verbal, unlike Twin A who is wheelchair-bound, severely retarded, nonverbal, and autistic. Abnormal eye movements and retinal dysplasia are striking features in all three girls, but none has renal cysts seen by ultrasonography. Magnetic resonance images show the "molar tooth sign," the radiologic hallmark of Joubert syndrome, although only one twin, the most severely handicapped, has severe hypoplasia of the cerebellar hemispheres. Phenotypic differences between the twins could be attributable to postzygotic unequal division of the inner cell mass, unequal sharing of the venous return from a monochorionic placenta, mosaicism, or a mutation of a modifying gene.
Raynes
H R
HR
Department of Neurology, Jacobi and Montefiore Medical Centers, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10467, USA. goldraynes@aol.com
Shanske
A
A
Goldberg
S
S
Burde
R
R
Rapin
I
I
D002531:Cerebellum / Q000002:abnormalities*; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics*; D004200:Diseases in Twins / Q000235:genetics*; D005260:Female; D005317:Fetal Growth Retardation / Q000175:diagnosis / Q000235:genetics; D005500:Follow-Up Studies; D020546:Fourth Ventricle / Q000002:abnormalities / Q000473:pathology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D009460:Neurologic Examination; D010641:Phenotype; D011247:Pregnancy; D020754:Spinocerebellar Ataxias / Q000175:diagnosis / Q000235:genetics*; D013577:Syndrome; D014430:Twins, Monozygotic