Array-CGH analysis in a patient with Acrocallosal Syndrome

We present a patient aged 3 years with a clinical diagnosis of acrocallosal syndrome (ACS) and a complex chromosomal rearrangement (CCR). Pregnancy was unremarkable, except for the detection of corpus callosum agenesis in the second trimester. At birth, weight, length, OFC and Apgar scores were all within normal limits. Severe hypotonia, hypertelorism, strabismus and nystagmus, short philtrum, micrognathia, broad thumbs and toes associated with absence of intermediate and distal phalanges of fifth finger, talipes varus and micropenis were noted. Abdominal ultrasound examination detected bilateral kidney malrotation and bilateral vescico-ureteral reflux. Agenesis of corpus callosum was subsequently confirmed by cerebral MRI. Karyotype was 46,XY; Prader-Willi syndrome and mithocondrial disorders were ruled out. A complex chromosomal rearrangement consisting with a deletion (12)(p12.2p2.1) and a duplication (16)(q23.3) was detected by a-CGH analysis. Interestingly, the deletion and the duplication have been inherited from the phenotypically normal mother and father respectively and they are not described as polymorphic variants. The CCR detected in our patient has never been associated with ACS, but being inherited by phenotypically normal parents, its pathogenetic role is not clear and it is open to speculation.