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Abstract #28236 Published in IGR 13-1
Reiger anomaly due to a FOXC1 gene deletion: Look beyond the eyes
Hanna B; Rajagopalan STwin Research and Human Genetics: the Official Journal of the International Society for Twin Studies 2010; 13: 642
Axenfeld-Rieger (AR) malformations are developmental defects of the anterior segment of the eye, associated with a high risk of glaucomatous blindness. A proportion of affected individuals have syndromic features (termed Axenfeld-Rieger syndrome or ARS), which include distinctive craniofacial dysmorphology, dental anomalies, umbilical herniae and redundant periumbilical skin. Heterozygous germline mutations of two genes, the forkhead transcription factor gene FOXC1 (6p25) and PITX2 (4q25) have been proven to cause ARS. Haploinsufficiency through deletion of FOXC1 has also been reported in ARS, and this may be part of a contiguous 6p25 terminal or interstitial deletion. Contiguous deletions encompassing FOXC1 may also cause congenital heart disease, cerebellar and renal anomalies, hearing loss and developmental delay. This case report presents a 12-month old boy with bilateral Rieger anomaly. On initial assessment at age 7 months, he had striking dysmorphic features including microcephaly, plagiocephaly, telecanthus, hypertelorism, proptosis, malar hypoplasia, pre-auricular skin tags, widely spaced nipples and pectus excavatum. He had a normal male karyotype. Array CGH using 60k ISCA Oligoarray detected a de novo interstitial microdeletion spanning 1 Mb in size in chromosome 6p25, which encompasses the FOXC1 gene and GMDS gene. The child is now receiving treatment for glaucoma and appears to be developing normally to date. We have recommended imaging of the central nervous system and audiology testing to clarify the presence of any extra-ocular manifestations as seen in 6p25 microdeletion syndromes. The presence of an Axenfeld-Reiger anomaly, in combination with a characteristic facial gestalt, should raise clinical suspicion of a chromosome 6p25 deletion encompassing the FOXC1 gene. Investigation with a high-resolution array CGH is recommended to elucidate the genetic aetiology in these individuals, which in turn may help target specific surveillance for non-ocular manifestations.
B. Hanna. SSWAHS Liverpool Hospital, Sydney, Australia.
Classification:
9.1.3 Syndromes of Axenfeld, Rieger, Peters, aniridia (Part of: 9 Clinical forms of glaucomas > 9.1 Developmental glaucomas)
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
9.4.15 Glaucoma in relation to systemic disease (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders)
