According to the underlying etiology our suspected OAVS cases Essay

According to the underlying etiology, our suspected OAVS cases were classified into 3 subgroups:

IIa: group with unknown etiology (cases 10-40)

IIb: group with teratogenic insult (cases 41, 42)

IIc: group with chromosomal etiology (cases 43-45)

Most OAV spectrum cases are sporadic with no relevant family history. However, a genetic predisposition has been proposed based on growing evidence from the literature (Goodin et al., 2009; Tasse et al., 2007). It is noteworthy that a report by Rooryck et al. (C. Rooryck et al., 2010) identified 12% of familial cases in a cohort of 95 patients.

An additional clinical study by Rollnick et al. (B. R. Rollnick & Kaye, 1983) has presented pedigree data on 97 cases, 44 of whom had a family history of the same or similar anomaly, even if it was only minor OAVS manifestations (minor external ear anomalies or preauricular tag being the most common). Furthermore, the authors observe a broad phenotypic spectrum within families, an aspect that has also been reported by others (B. Rollnick et al., 1988).

Different chromosomal anomalies have been identified by standard karyotyping or array comparative genomic hybridisation in OAVS patients (C.

Rooryck et al., 2010) The association with chromosomes 5, 9, 18, 22 and X was observed on several occasions(R. Hennekam, Krantz, & Allanson, 2010). Numeric chromosomes anomalies have been shown, such as mosaic trisomies of chromosomes 9 and 22 (T. de Ravel et al., 2001; Garavelli et al., 1999; Wilson & Barr, 1983) and chromosome X aneuploidy (Garavelli et al., 1999) .

In the current study, group IIc comprising cases (43-45) were diagnosed to have chromosomal anomalies. Case 43 is a Down syndrome female patient with features of OAVS. This is not a previously reported combination to the best of our knowledge and to the best of our knowledge; no previous publications mentioned these features even as incidental findings .Further delineation of genes on chromosome 21 that may be implicated in OAVS may be a future research interest.

Case 44 showed the typical features of OAVS and Klinefelter syndrome. Garavelli et al. reported a boy with classical 47, XXY Klinefelter syndrome (KS) and OAVS. Two patients with KS and OAVS were reported previously. Also, the combination of bilateral mandibular ramus and condyle aplasia and KS has been documented. The present observation supports the view that the cause of hemifacial microsomia appears heterogeneous and that OAV may be part of the spectrum of craniofacial anomalies associated with KS(Garavelli et al., 1999).

Case 45 with minimal features of the spectrumin addition to brain atrophic changes revealed abnormal chromosome 8 with added chromosomal material to its short arm which is a result of maternal balanced reciprocal translocation between chromosomes 8 and 12 at bands p23 and p11.2. This is a novel imbalance not reported before to be implicated in OAVS. Array CGH was performed to the patient to allocate the exact size and intervals of the imbalance and detect genes that may suspect to be causative for the phenotype. This will be discussed in details with the array CGH results.