Molar tooth sign of the midbrain-hindbrain junction: occurrence in multiple distinct syndromes.
The Molar Tooth Sign (MTS) is defined by an abnormally deep interpeduncular fossa; elongated, thick, and mal-oriented superior cerebellar peduncles; and absent or hypoplastic cerebellar vermis that together give the appearance of a "molar tooth" on axial brain MRI through the junction of the midbrain and hindbrain (isthmus region). It was first described in Joubert syndrome (JS) where it is present in the vast majority of patients with this diagnosis. We previously showed that the MTS is a component of several other syndromes, including Dekaban-Arima (DAS), Senior-Löken, and COACH (cerebellar vermis hypoplasia (CVH), oligophrenia, ataxia, coloboma, and hepatic fibrosis). Here we present evidence that the MTS is seen together with polymicrogyria, Váradi-Papp syndrome (Orofaciodigital VI (OFD VI)), and a new syndrome with encephalocele and cortical renal cysts. We also present a new patient with COACH syndrome plus the MTS. We propose that the MTS is found in multiple distinct clinical syndromes that may share common developmental mechanisms. Proper classification of patients with these variants of the MTS will be essential for localization and identification of mutant genes.
Gleeson
Joseph G
JG
Division of Pediatric Neurology, Department of Neurosciences, University of California, San Diego, California 92093-0624, USA. jogleeson@ucsd.edu
Keeler
Lesley C
LC
Parisi
Melissa A
MA
Marsh
Sarah E
SE
Chance
Phillip F
PF
Glass
Ian A
IA
Graham
John M
JM
Maria
Bernard L
BL
Barkovich
A James
AJ
Dobyns
William B
WB
D000015:Abnormalities, Multiple / Q000175:diagnosis*; D001921:Brain / Q000002:abnormalities* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D010375:Pedigree; D013577:Syndrome