The first child (proband) of nonconsanguineous Caucasian parents underwent genetic investigation because she was affected with congenital
choanal atresia, heart defects and kidney hyposplasia with mild transient
renal insufficiency. The direct
DNA sequencing after PCR of the CHD7 gene, which is thought to be responsible for approximately 60-70% of the cases of
CHARGE syndrome/association, found no mutations. The cytogenetic analysis (standard GTG banding karyotype) revealed the presence of extrachromosomal material on 10q. The chromosome analysis was completed with array CGH (30 kb resolution), MLPA and FISH, which allowed the identification of three 6p regions (6p.25.3p23 × 3): 2 of these regions are normally located on chromosome 6, and the third region is translocated to the long arm of chromosome 10. The same chromosomal rearrangement was subsequently found in the father, who was affected with congenital ptosis and progressive
hearing loss, and in the proband's sister, the second child, who presented at birth with
choanal atresia and
congenital heart defects. The mutated karyotypes, which were directly inherited, are thought to be responsible for a variable phenotype, including craniofacial dysmorphisms,
choanal atresia, congenital ptosis,
sensorineural hearing loss, heart defects, developmental delay, and renal dysfunction. Nevertheless, to achieve a complete audiological assessment of the father, he underwent further investigation that revealed an increased level of the
coagulation factor XIII (300% increased activity), fluctuating levels of
fibrin D-dimer degradation products (from 296 to 1,587 ng/ml) and a homoplasmic
mitochondrial DNA mutation: T961G in the MTRNR1 (
12S rRNA) gene. He was made a candidate for
cochlear implantation. Preoperative high-resolution computed tomography and magnetic resonance imaging of the temporal bone revealed the presence of an
Arnold-Chiari malformation type I. To the best of our knowledge, this study is the second report on partial 6p
trisomy that involves the 10q terminal region. Furthermore, we report the first case of documented
Arnold-Chiari malformation type I and increased
factor XIII activity associated with 6p
trisomy. We present a comprehensive report of the familial cases and an exhaustive literature review.