Delineation and Diagnostic Criteria of Oral-Facial-Digital Syndrome Type VI

Orphanet Journal of Rare Diseases

Eugen Boltshauser^1,18  Enza Maria Valente⁹  Daniel Tibussek^1,10  Ronen Spiegel^1,19  Christoph E Schwarz^1,13  Ianina Scheer⁸  Romina Romaniello⁷  Lorenzo Pinelli⁵  Melissa M Lees^1,12  Magnus Landgren^2,20  Marten Kyllerman^1,17  Gerhard Kluger^1,15  Miriam Iannicelli⁹  Thierry AGM Huisman⁴  Lucio Giordano^1,11  Francesca Faravelli²  Stefano D'Arrigo^1,14  Francesco Brancati³  Renato Borgatti⁷  Enrico Bertini⁶  Filippo Arrigoni^1,16  Raoul CM Hennekam¹  Giuseppina Vitiello⁹  Andrea Poretti⁴ 

[1] Department of Pediatrics, Academic Medical Centre, Amsterdam, The Netherlands;Department of Medical Genetics, Ospedale Galliera, Genoa, Italy;Department of Biomedical Sciences, Ce.S.I. Aging Research Center, Gabriele d'Annunzio University Foundation, Chieti, Italy;Division of Pediatric Radiology, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA;Division of Neuroradiology, Spedali Civili, Brescia, Italy;Unit of Molecular Medicine, Department of Neurosciences, Bambino Gesù Hospital, Rome, Italy;Department of Neurorehabilitation 1, Scientific Institute 'E. Medea', Bosisio Parini (LC), Italy;Division of Diagnostic Imaging, University Children's Hospital of Zurich, Switzerland;Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza Institute, San Giovanni Rotondo, Italy;Department of General Pediatrics, University Children's Hospital, Düsseldorf, Germany;Division of Child Neurology, Spedali Civili, Brescia, Italy;Clinical Genetics Unit, Great Ormond Street Hospital for Children, London, UK;Department of Neonatology, University Children's Hospital, Tübingen, Germany;Department of Developmental Neurology, IRCCS Istituto Neurologico C. Besta, Milan, Italy;Paracelsus Medical University, Salzburg, Austria;Department of Neuroradiology, Scientific Institute 'E. Medea', Bosisio Parini (LC), Italy;Department of Neuropaediatrics, The Queen Silvia Children's Hospital, Sahlgrenska University, Gothenberg, Sweden;Department of Pediatric Neurology, University Children's Hospital of Zurich, Switzerland;Department of Pediatrics A, HaEmek Medical Center, Afula and Rappaport School of Medicine, Haifa, Israel;Department of Pediatrics, Developmental Neurology, Skaraborg Hospital, Skövde, Sweden

关键词: cerebellar malformation;    molar tooth sign;    neuroimaging;    Oral-facial-digital syndrome type VI;    Joubert syndrome and related disorders;   

Others  :  864467
DOI  :  10.1186/1750-1172-7-4

 received in 2011-09-09, accepted in 2012-01-11,  发布年份 2012

【 摘 要 】

Oral-Facial-Digital Syndrome type VI (OFD VI) represents a rare phenotypic subtype of Joubert syndrome and related disorders (JSRD). In the original report polydactyly, oral findings, intellectual disability, and absence of the cerebellar vermis at post-mortem characterized the syndrome. Subsequently, the molar tooth sign (MTS) has been found in patients with OFD VI, prompting the inclusion of OFD VI in JSRD. We studied the clinical, neurodevelopmental, neuroimaging, and genetic findings in a cohort of 16 patients with OFD VI. We derived the following inclusion criteria from the literature: 1) MTS and one oral finding and polydactyly, or 2) MTS and more than one typical oral finding. The OFD VI neuroimaging pattern was found to be more severe than in other JSRD subgroups and includes severe hypoplasia of the cerebellar vermis, hypoplastic and dysplastic cerebellar hemispheres, marked enlargement of the posterior fossa, increased retrocerebellar collection of cerebrospinal fluid, abnormal brainstem, and frequently supratentorial abnormalities that occasionally include characteristic hypothalamic hamartomas. Additionally, two new JSRD neuroimaging findings (ascending superior cerebellar peduncles and fused thalami) have been identified. Tongue hamartomas, additional frenula, upper lip notch, and mesoaxial polydactyly are specific findings in OFD VI, while cleft lip/palate and other types of polydactyly of hands and feet are not specific. Involvement of other organs may include ocular findings, particularly colobomas. The majority of the patients have absent motor development and profound cognitive impairment. In OFD VI, normal cognitive functions are possible, but exceptional. Sequencing of known JSRD genes in most patients failed to detect pathogenetic mutations, therefore the genetic basis of OFD VI remains unknown. Compared with other JSRD subgroups, the neurological findings and impairment of motor development and cognitive functions in OFD VI are significantly worse, suggesting a correlation with the more severe neuroimaging findings. Based on the literature and this study we suggest as diagnostic criteria for OFD VI: MTS and one or more of the following: 1) tongue hamartoma(s) and/or additional frenula and/or upper lip notch; 2) mesoaxial polydactyly of one or more hands or feet; 3) hypothalamic hamartoma.

【 授权许可】

   
2012 Poretti et al; licensee BioMed Central Ltd.

【 图 表 】

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