Acro‐cardio‐facial syndrome: A microdeletion syndrome?

Abstract

Acro-cardio-facial syndrome (ACFS) is an infrequently reported, variable condition characterized by split-hand and split-foot malformation and congenital heart defect (CHD), along with cleft lip and palate, genital anomalies, unusual face and intellectual disability. An autosomal recessive pattern of inheritance has been suggested because of affected sibs born to unaffected parents and parental consanguinity; the cause is unknown. We describe a newborn with the clinical manifestations of ACFS in whom a deletion of the region 6q21-q22.3 was detected by array CGH. We compare the clinical features of the present patient with earlier reported patients with similar 6q deletions and patients diagnosed with ACFS. The similarities between these patient groups suggest that ACFS may be a microdeletion syndrome caused by loss of the 6q21-22.3 region. The recurrence in families may be explained by prenatal germline mosaicism. Alternatively, ACFS may be a genetically heterogeneous disorder which can also be caused by biallelic mutations of an autosomal recessive gene.

Positional mapping ofPRKD1,NRP1andPRDM1as novel candidate disease genes in truncus arteriosus

“…More importantly, while Prdm1 −/− is embryonic lethal, conditional Sox2 -Cre-driven deletion of Prdm1 results in a number of anomalies including TA, the same CHD we observe in the patient with haploinsufficiency for PRDM1 that we report here 41. Furthermore, a patient with TA was reported to have de novo deletion on 6q with the following coordinates 106 543 543–119 109 372 42. When combined with our deletion, we can determine the critical deletion interval for TA phenotype to be 106 543 543–10 773 7955, which still includes PRDM1 (among others).…”

Clinical, genetic, and molecular aspects of split‐hand/foot malformation: An update

“…A microdeletion at the 6q21-q22 region has been reported in a patient with this condition [Toschi et al, 2012]. Autosomal recessive inheritance is likely.…”

“…However, its role in causing SHFM is not clear, as SNX3 mutations have not been identified in other patients with syndromal SHFM and overlapping clinical features [Kumar et al, 2007]. A 12.5 Mb deletion at 6q21-q22.31 that included SNX3 was recently identified in a patient with the acro-cardio-facial syndrome [Toschi et al, 2012]. The 6q16-q22 region was also suggested as a candidate SHFM locus based on a statistical analysis of patients reported in the Human Cytogenetic Database [Niedrist et al, 2009].…”

Confirmation of 6q21–6q22.1 deletion in Acro‐cardio‐facial syndrome and further delineation of this contiguous gene deletion syndrome

“…In the past, autosomal recessive inheritance has been suggested following observation of parental consanguinity and affected siblings in few families [Guion-Almeida et al, 2000; Mingarelli et al, 2005; Digilio and Dallapiccola, 2010]. More recently Toschi et al [2012] proposed that ACFS may be a new microdeletion syndrome based on a 6q21–22.3 microarray deletion identified in an affected child. The authors reviewed reported cases of chromosome deletions in the 6q region, and found the clinical spectrum of anomalies consistent with ACFS [Toschi et al, 2012].…”