Subtelomeric 6p deletion: Clinical, FISH, and array CGH characterization of two cases

Abstract

Thirty patients have been described with cytogenetically visible deletion of the short arm of chromosome 6. However, subtelomeric 6p deletion detected by subtelomeric specific probes has been reported only twice. We report two new patients with terminal 6p deletion detected by subtelomeric screening using fluorescence in situ hybridization (FISH). The two patients exhibited mental retardation, ocular abnormalities, hearing loss, and a characteristic facial appearance. Detailed FISH analyses with probes covering the distal 6p25 region estimated the size of the terminal deletions to approximately 5.5 Mb and approximately 4.8 Mb. Array-based comparative genomic hybridization (array CGH) was used to confirm the cryptic deletions. Most patients with subtelomeric defects lack a characteristic phenotype. However, some of the subtelomeric deletions result in a specific phenotype, which can direct the clinician towards the diagnosis. Submicroscopic 6p deletion appears to be a recognizable clinical phenotype, and this region should be thoroughly investigated with FISH probes, including at least a subtelomeric 6p probe and a probe covering FOXC1, for patients presenting with a characteristic facial appearance, ocular abnormalities, predominantly anterior-chamber eye defects, hearing loss, and mental retardation.

Schizophrenia in an adult with 6p25 deletion syndrome

“…A normal karyotype in infancy, normal vision, few other health problems and lack of genetics followup likely contributed to lack of recognition of a diagnosable syndrome until she was specifically assessed as an adult. The case supports recent evidence that 6p25 deletion syndrome has a recognizable clinical phenotype and supports recommendations for thorough investigations including FISH for patients presenting with characteristic features [Davies et al, 1999b;Le Caignec et al, 2005;Maclean et al, 2005].…”

“…Table II presents a summary of this patient in the context of previous reports of adults and adolescents with distal 6p deletions [Jalal et al, 1989;Palmer et al, 1991;Law et al, 1998;Davies et al, 1999b;Le Caignec et al, 2005]. The patient presented in this report has many typical features of 6p25 deletion syndrome, and appears to have greatest similarity to patient SG in Law et al, 1998 and patient 3 in Mirza et al, 2004, with respect to the phenotype and extent of deletion [Law et al, 1998;Mirza et al, 2004].…”

Axenfeld–Rieger syndrome and spectrum of PITX2 and FOXC1 mutations

“…45,46 Balanced chromosome rearrangements involving FOXC1 or its surrounding landscape are rare, but a balanced t(6;13) translocation in an ARS patient lead to identification of FOXC1, as a causative gene for this disorder. 11 On the other hand, there are more than 40 deletions, either interstitial or telomeric, involving 6p25 45,47,48 and the patients frequently present with ocular, craniofacial, skeletal, cardiac, and renal malformations, hearing loss, and hydrocephalus. 47 The phenotypic variation seen in these patients are largely because of the size of the deletions and the genes involved.…”

“…11 On the other hand, there are more than 40 deletions, either interstitial or telomeric, involving 6p25 45,47,48 and the patients frequently present with ocular, craniofacial, skeletal, cardiac, and renal malformations, hearing loss, and hydrocephalus. 47 The phenotypic variation seen in these patients are largely because of the size of the deletions and the genes involved. Ocular anomalies of the anterior segment, such as posterior embryotoxon and iris hypoplasia, are commonly observed in these patients, and these are attributed to the deletion of the FOXC1 gene or its regulatory elements.…”

Cortical dysplasia and skull defects in mice with a Foxc1 allele reveal the role of meningeal differentiation in regulating cortical development

“…ARS is characterized by dysgenesis of the anterior segment of the eye and is often associated with craniofacial abnormalities and abnormal dentition. ARS has also presented as an autosomal recessive disorder with mental retardation, hydrocephalus, and meningeal calcification (12) or as part of a chromosomal deletion syndrome (including Foxc1 and possibly other genes) associated with mental retardation and hydrocephalus (13)(14)(15).…”