title: The 6p25 deletion syndrome: An update on a rare neurocristopathy.
abstract: Anterior segment dysgeneses are developmental anomalies of the anterior eye segment that can occur as isolated defects or as part of various syndromes. A subgroup is caused by abnormal embryonic neural crest development. The Axenfeld-Rieger syndrome is an umbrella term for a continuum of anterior segment dysgeneses of neural crest origin, characterized by the presence of the Axenfeld or Rieger eye malformation predisposing for glaucoma. Additionally, other structures of neural crest origin can be variably affected giving rise to a wide spectrum of associated extra-ocular malformations. Key clinical features comprise facial dysmorphism including mid-face and dental hypoplasia, hearing loss, cardiac anomalies, and involuted periumbilical skin. The Axenfeld-Rieger syndrome is genetically heterogeneous and about 16% of cases are caused by heterozygous mutations in FOXC1 at 6p25.3, a transcription factor gene regulating neural crest cell development. There is considerable clinical overlap between the Axenfeld-Rieger syndrome and the 6p25 deletion syndrome, a microdeletion syndrome characterized by heterozygous loss of FOXC1. In both syndromes, FOXC1 haploinsufficiency seems to be pathogenic. Here, we review the clinical features and pathogenesis of the 6p25 deletion syndrome.
authors.affiliation: a Department of Clinical Genetics and School for Oncology and Developmental Biology (GROW) , Maastricht University Medical Center+ , Maastricht , the Netherlands.
authors.forename: Ivo J H M
authors.initials: IJ
authors.lastname: de Vos
authors.affiliation: a Department of Clinical Genetics and School for Oncology and Developmental Biology (GROW) , Maastricht University Medical Center+ , Maastricht , the Netherlands.
authors.forename: Alexander P A
authors.initials: AP
authors.lastname: Stegmann
authors.affiliation: b Department of Ophthalmology , Maastricht University Medical Center+ , Maastricht , the Netherlands.
authors.forename: Carroll A B
authors.initials: CA
authors.lastname: Webers
authors.affiliation: a Department of Clinical Genetics and School for Oncology and Developmental Biology (GROW) , Maastricht University Medical Center+ , Maastricht , the Netherlands.
authors.forename: Constance T R M
authors.initials: CT
authors.lastname: Stumpel
mesh_terms: D000869:Anterior Eye Segment / Q000002:abnormalities*; D002872:Chromosome Deletion; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005124:Eye Abnormalities / Q000175:diagnosis* / Q000235:genetics; D015785:Eye Diseases, Hereditary; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D006801:Humans; D009432:Neural Crest / Q000473:pathology*; D055815:Young Adult
chemical_list: C112743:FOXC1 protein, human; D051858:Forkhead Transcription Factors
keywords: 6p25 deletion; Axenfeld-Rieger syndrome; neurocristopathy