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Cardiac anomalies in Axenfeld-Rieger syndrome due to a novel FOXC1 mutation.
Am J Med Genet A. 2013 Jan; 161A(1):114-9.AJ

Abstract

Axenfeld-Rieger syndrome (ARS) is an autosomal dominant condition characterized by ophthalmologic anterior segment abnormalities and extraocular findings including dental anomalies and redundant periumbilical skin. Intragenic mutations in the homeobox gene PITX2 or the transcription factor encoding FOXC1 were identified, and genomic rearrangements encompassing either gene also cause ARS. A molecular etiology is identified in 40-60%. Extraocular anomalies occur more often with intragenic PITX2 than FOXC1 mutations. We report on a patient with infantile glaucoma presenting at age 21 months with congestive heart failure due to a dysplastic arcade mitral valve necessitating valve replacement, and mildly hypoplastic left ventricular outflow tract and aortic arch. Family history included early onset glaucoma in four relatives; congenital hip dysplasia requiring surgery in three; and an atrial septal defect in the affected maternal grandmother. Despite the absence of dental or umbilical abnormalities, anterior chamber abnormalities consistent with ARS were present in affected individuals. Molecular testing revealed a novel FOXC1 mutation (c.508C>T; p.Arg170Trp) in the proband and his affected mother; other family members were unavailable. A literature review revealed four reports of congenital heart disease associated with intragenic FOXC1 mutations, and none with intragenic PITX2 mutations. Previously, mouse studies showed Foxc1 (Mf1) expression in the developing valves and atrial septum, supporting a causal relationship of FOXC1 mutations for valvar anomalies and ASD. Hip dysplasia in three family members suggests a role for FOXC1 in the femoral head dysplasia of de Hauwere syndrome with 6p25 deletions. Further reports of clinical and molecular diagnoses will clarify genotype-phenotype correlation.

Authors+Show Affiliations

Division of Medical Genetics, A. I. DuPont Hospital for Children, Wilmington, Delaware. kgripp@nemours.org.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

23239455

Citation

Gripp, Karen W., et al. "Cardiac Anomalies in Axenfeld-Rieger Syndrome Due to a Novel FOXC1 Mutation." American Journal of Medical Genetics. Part A, vol. 161A, no. 1, 2013, pp. 114-9.
Gripp KW, Hopkins E, Jenny K, et al. Cardiac anomalies in Axenfeld-Rieger syndrome due to a novel FOXC1 mutation. Am J Med Genet A. 2013;161A(1):114-9.
Gripp, K. W., Hopkins, E., Jenny, K., Thacker, D., & Salvin, J. (2013). Cardiac anomalies in Axenfeld-Rieger syndrome due to a novel FOXC1 mutation. American Journal of Medical Genetics. Part A, 161A(1), 114-9. https://doi.org/10.1002/ajmg.a.35697
Gripp KW, et al. Cardiac Anomalies in Axenfeld-Rieger Syndrome Due to a Novel FOXC1 Mutation. Am J Med Genet A. 2013;161A(1):114-9. PubMed PMID: 23239455.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardiac anomalies in Axenfeld-Rieger syndrome due to a novel FOXC1 mutation. AU - Gripp,Karen W, AU - Hopkins,Elizabeth, AU - Jenny,Kim, AU - Thacker,Deepika, AU - Salvin,Jonathan, Y1 - 2012/12/14/ PY - 2012/07/13/received PY - 2012/09/09/accepted PY - 2012/12/15/entrez PY - 2012/12/15/pubmed PY - 2013/6/20/medline SP - 114 EP - 9 JF - American journal of medical genetics. Part A JO - Am J Med Genet A VL - 161A IS - 1 N2 - Axenfeld-Rieger syndrome (ARS) is an autosomal dominant condition characterized by ophthalmologic anterior segment abnormalities and extraocular findings including dental anomalies and redundant periumbilical skin. Intragenic mutations in the homeobox gene PITX2 or the transcription factor encoding FOXC1 were identified, and genomic rearrangements encompassing either gene also cause ARS. A molecular etiology is identified in 40-60%. Extraocular anomalies occur more often with intragenic PITX2 than FOXC1 mutations. We report on a patient with infantile glaucoma presenting at age 21 months with congestive heart failure due to a dysplastic arcade mitral valve necessitating valve replacement, and mildly hypoplastic left ventricular outflow tract and aortic arch. Family history included early onset glaucoma in four relatives; congenital hip dysplasia requiring surgery in three; and an atrial septal defect in the affected maternal grandmother. Despite the absence of dental or umbilical abnormalities, anterior chamber abnormalities consistent with ARS were present in affected individuals. Molecular testing revealed a novel FOXC1 mutation (c.508C>T; p.Arg170Trp) in the proband and his affected mother; other family members were unavailable. A literature review revealed four reports of congenital heart disease associated with intragenic FOXC1 mutations, and none with intragenic PITX2 mutations. Previously, mouse studies showed Foxc1 (Mf1) expression in the developing valves and atrial septum, supporting a causal relationship of FOXC1 mutations for valvar anomalies and ASD. Hip dysplasia in three family members suggests a role for FOXC1 in the femoral head dysplasia of de Hauwere syndrome with 6p25 deletions. Further reports of clinical and molecular diagnoses will clarify genotype-phenotype correlation. SN - 1552-4833 UR - https://www.unboundmedicine.com/medline/citation/23239455/Cardiac_anomalies_in_Axenfeld_Rieger_syndrome_due_to_a_novel_FOXC1_mutation_ DB - PRIME DP - Unbound Medicine ER -