Titel: Unexpected Array CGH result in a patient with leading symptom ocular coloboma
ID: P-ClinG-046
Art: Postertalk
Redezeit: 2 min
Session: Poster Session
ClinG 2

Referent: Kirsten Cremer (Bonn/DE), Hartmut Engels (Bonn/DE), Jessica Trautmann (Bonn/DE)

Abstract - Text


Background: Ocular colobomata are caused by a failure of the embryonic fissure to close during development. They are characteristically variable in appearance - affecting in varying degree the iris, choroid and/or optic nerve of one or both eyes. Ocular colobomata can occur isolated, but is often associated with other, systemic anomalies in particular of the central nervous system. In recent years, a large number of pathogenic variants in different genes have been identified. A large proportion of isolated ocular coloboma, however, remains idiopathic, without a confirmed genetic or environmental cause.

Case Report: We report on a 31-year-old male with bilateral retinal, choroidal, iris colobomata, mild facial dysmorphism and premature graying of the hair. The patient furthermore reported an aplasia of the 12th rib on the left side and cysts in the jaw.

Results: Cytogenetic banding analysis gave a normal male karyotype (46,XY). Notably, no cell with an additional marker chromosome was found in 50 mitoses evaluated, resulting in no evidence of an isodicentric chromosome derivative 22 (Cat Eye syndrome). Microarray CGH analysis and supplementary qPCR analyses in the parents identified a de novo interstitial heterozygous deletion of max. 3.47 Mb in chromosome subbands 6p24.3-p24.1 encompassing the gene TFAP2A as well as 24 additional genes. Heterozygous pathogenic mutations in TFAP2A cause the rare autosomal dominant Branchiooculofacial syndrome (BOFS, MIM # 113620). The clinical presentation is extremely variable: typical symptoms include branchial skin defects, abnormalities of the eyes (e.g. colobomata, microphthalmia), nasolacrimal duct stenosis / atresia and facial dysmorphism. Other reported abnormalities include subcutaneous cysts, dental abnormalities, and premature hair graying. Intellect is usually normal. Thus, we were able to diagnose the patient with BOFS.

Conclusion: More than 95% of mutations in patients with BOFS are single nucleotide variants or small intragenic deletions / insertions. Here we present a de novo deletion in 6p24.3-p24.1 encompassing TFAP2A identified by array CGH as a rare cause of BOFS. Our case shows the value of array diagnostics even in patients without the classical chromosomal microarray indication of neurodevelopmental disorders.