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Letters to the Editor / Pediatric Neurology 50 (2014) e15ee16
Eugen Boltshauser, MD Division of Pediatric Neurology University Children’s Hospital Zurich, Switzerland Enza Maria Valente, MD, PhD Mendel Laboratory IRCCS Casa Sollievo della Sofferenza Institute San Giovanni Rotondo, Italy Department of Medicine and Surgery University of Salerno Salerno, Italy
http://dx.doi.org/10.1016/j.pediatrneurol.2013.11.003
Clinical Syndromes or Ciliopathies Associated With Molar Tooth Sign To the Editor: We have read with interest the letter to the Editor by Poretti et al.1 regarding our publication “Molar tooth sign is not pathognomonic for Joubert syndrome.”2 We agree with the authors that a distinction between Joubert syndrome, Joubert syndrome-related disorders, and individual syndromes included in the Joubert syndrome-related disorders does not appear to contribute to the diagnostic definition of patients and may be confusing. The authors suggested a less confusing and clinically more relevant nomenclature, which uses only the term Joubert syndrome and adopt a descriptive classification based on the extent of involvement.3 All patients with Joubert syndrome-related disorders have molar tooth sign but most of these patients do not have the typical clinical features of the disease including episodic hyperpnea, abnormal eye movements, ataxia, and intellectual disability. For instance, only a small portion of patients with Varadi Papp syndrome reveal the neurological features of Joubert syndrome and diagnostic criteria for Varadi Papp syndrome does not involve any of these features.4 Similarly, Senior Loken syndrome is mainly characterized by the combination of two specific features: a kidney condition called nephronophthisis and an eye
condition known as Leber congenital amaurosis. Examples may be multiplied for cerebello-oculo-renal syndrome, Debakan-Arima syndrome, and COACH syndrome. In fact, most of the disorders labeled as Joubert syndrome-related disorders are ciliopathies and shared clinical features variably include retinal dystrophy, nephronophthisis, cystic dysplastic kidneys, congenital liver fibrosis, polydactyly, situs inversus, and midline oral and facial defects.3 On the other hand, the term “pathognomonic” means that a finding is so specific that is never seen in another condition. However, molar tooth sign is observed in Joubert syndromerelated disorders and some ciliopathies other than Joubert syndrome. In conclusion, the nomenclature of Joubert syndromerelated disorders should be questioned because most of the patients do not reveal clinical features of Joubert syndrome except molar tooth sign. It may be better to use terms such as “clinical syndromes or ciliopathies associated with molar tooth sign.”
References 1. Poretti A, Boltshauser E, Valente EM. Molar tooth sign is pathognomonic for Joubert syndrome!. Pediatr Neurol; 2013. (Epub ahead of print). 2. Dirik M, Yis U, Dirik E. Molar tooth sign is not pathognomonic for Joubert syndrome. Pediatr Neurol; 2013. (Epub ahead of print). 3. Romani M, Micalizzi A, Valente EM. Joubert syndrome: congenital cerebellar ataxia with molar tooth. Lancet Neurol. 2013;12:894-905. 4. Poretti A, Vitiello G, Hennekam RC, et al. Delineation and diagnostic criteria of Oral-Facial-Digital Syndrome type VI. Orphanet J Rare Dis. 2012;7:4.
Uluç Yis¸, MD Division of Child Neurology, Department of Pediatrics, School of _ Medicine, Dokuz Eylül University, Izmir, Turkey E-mail address: [email protected] Mehmet Alp Dirik, MD _ Açık Radio Imaging Center, Izmir, Turkey Eray Dirik, MD Division of Child Neurology, Department of Pediatrics, Near East University, Lefkos¸a, Turkish Republic of Northern Cyprus
http://dx.doi.org/10.1016/j.pediatrneurol.2013.11.023
Letters to the Editor / Pediatric Neurology 50 (2014) e15ee16
Eugen Boltshauser, MD Division of Pediatric Neurology University Children’s Hospital Zurich, Switzerland Enza Maria Valente, MD, PhD Mendel Laboratory IRCCS Casa Sollievo della Sofferenza Institute San Giovanni Rotondo, Italy Department of Medicine and Surgery University of Salerno Salerno, Italy
http://dx.doi.org/10.1016/j.pediatrneurol.2013.11.003
Clinical Syndromes or Ciliopathies Associated With Molar Tooth Sign To the Editor: We have read with interest the letter to the Editor by Poretti et al.1 regarding our publication “Molar tooth sign is not pathognomonic for Joubert syndrome.”2 We agree with the authors that a distinction between Joubert syndrome, Joubert syndrome-related disorders, and individual syndromes included in the Joubert syndrome-related disorders does not appear to contribute to the diagnostic definition of patients and may be confusing. The authors suggested a less confusing and clinically more relevant nomenclature, which uses only the term Joubert syndrome and adopt a descriptive classification based on the extent of involvement.3 All patients with Joubert syndrome-related disorders have molar tooth sign but most of these patients do not have the typical clinical features of the disease including episodic hyperpnea, abnormal eye movements, ataxia, and intellectual disability. For instance, only a small portion of patients with Varadi Papp syndrome reveal the neurological features of Joubert syndrome and diagnostic criteria for Varadi Papp syndrome does not involve any of these features.4 Similarly, Senior Loken syndrome is mainly characterized by the combination of two specific features: a kidney condition called nephronophthisis and an eye
condition known as Leber congenital amaurosis. Examples may be multiplied for cerebello-oculo-renal syndrome, Debakan-Arima syndrome, and COACH syndrome. In fact, most of the disorders labeled as Joubert syndrome-related disorders are ciliopathies and shared clinical features variably include retinal dystrophy, nephronophthisis, cystic dysplastic kidneys, congenital liver fibrosis, polydactyly, situs inversus, and midline oral and facial defects.3 On the other hand, the term “pathognomonic” means that a finding is so specific that is never seen in another condition. However, molar tooth sign is observed in Joubert syndromerelated disorders and some ciliopathies other than Joubert syndrome. In conclusion, the nomenclature of Joubert syndromerelated disorders should be questioned because most of the patients do not reveal clinical features of Joubert syndrome except molar tooth sign. It may be better to use terms such as “clinical syndromes or ciliopathies associated with molar tooth sign.”
References 1. Poretti A, Boltshauser E, Valente EM. Molar tooth sign is pathognomonic for Joubert syndrome!. Pediatr Neurol; 2013. (Epub ahead of print). 2. Dirik M, Yis U, Dirik E. Molar tooth sign is not pathognomonic for Joubert syndrome. Pediatr Neurol; 2013. (Epub ahead of print). 3. Romani M, Micalizzi A, Valente EM. Joubert syndrome: congenital cerebellar ataxia with molar tooth. Lancet Neurol. 2013;12:894-905. 4. Poretti A, Vitiello G, Hennekam RC, et al. Delineation and diagnostic criteria of Oral-Facial-Digital Syndrome type VI. Orphanet J Rare Dis. 2012;7:4.
Uluç Yis¸, MD Division of Child Neurology, Department of Pediatrics, School of _ Medicine, Dokuz Eylül University, Izmir, Turkey E-mail address: [email protected] Mehmet Alp Dirik, MD _ Açık Radio Imaging Center, Izmir, Turkey Eray Dirik, MD Division of Child Neurology, Department of Pediatrics, Near East University, Lefkos¸a, Turkish Republic of Northern Cyprus
http://dx.doi.org/10.1016/j.pediatrneurol.2013.11.023
