Molar Tooth Sign of the Midbrain-Hindbrain Junction: Occurrence in Multiple Distinct Syndromes

Joseph G. Gleeson, Lesley C. Keeler, Melissa A. Parisi, Sarah E. Marsh, Phillip F. Chance, Ian A. Glass, John M. Graham, Bernard L. Maria, A. James Barkovich, William B. Dobyns

Research output: Contribution to journalArticlepeer-review

199 Scopus citations


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 MR1 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.

Original languageEnglish (US)
Pages (from-to)125-134
Number of pages10
JournalAmerican Journal of Medical Genetics
Volume125 A
Issue number2
StatePublished - Mar 1 2004
Externally publishedYes


  • Ataxia
  • Cerebellar vermis
  • Coloboma
  • Dekaban-Arima
  • Encephalocele
  • Hepatic fibrosis
  • Hypotonia
  • Joubert
  • Kidney cysts
  • Leber congenital amaurosis
  • Molar tooth
  • Nephronophthisis
  • OFD-VI
  • Oculomotor apraxia
  • Polymicrogyria
  • Senior-Löken
  • Váradi-Papp


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