Bowen-Conradi Syndrome

A number sign (#) is used with this entry because Bowen-Conradi syndrome (BWCNS) is caused by homozygous mutation in the EMG1 gene (611531) on chromosome 12p13.

Clinical Features

Among the offspring of second-cousin Hutterite parents, Bowen and Conradi (1976) described 2 males with a distinctive syndrome: prominent 'proud' nose, micrognathia, fifth finger clinodactyly, 'rocker-bottom' feet, and death in the first months of life. No autopsy information was available. Hunter et al. (1979) reported on 5 additional Hutterite cases. Low birth weight, microcephaly, and mild joint restriction were additional nonspecific features. The causative mutation appears to be widely distributed among the 3 North American sects (leuts) of Hutterites. Lowry et al. (2003) ascertained 39 cases of Bowen-Conradi syndrome, born during the 33-year period from 1968 to 2000, and personally examined almost all. The patients belonged to 29 nuclear families and were ascertained in all 3 leuts: 14 in Dariusleut, 12 in Schmiedeleut, and 3 in Lehrerleut.

Innes and Lowry (2002) cited 3 reports of possible Bowen-Conradi syndrome in non-Hutterite children. Lemire (2002) noted 2 non-Hutterite cases of this disorder. The first was reported by Le Marec et al. (1981) as an autosomal recessive phenocopy of trisomy 18 in a Turkish patient (case 13) and was subsequently identified as Bowen-Conradi syndrome. Another was reported by Gupta and Phadke (2001) in an Indian infant. Lemire (2002) suggested that Bowen-Conradi syndrome be considered in any infant with features compatible with the diagnosis, regardless of ethnicity.

Mapping

By linkage and haplotype analysis in 11 Canadian Hutterite families (8 Schmiedeleut and 3 Dariusleut), Lamont et al. (2005) mapped the Bowen-Conradi syndrome locus to a 3.5-cM segment on chromosome 12p13.3, bounded by VWF (613160) and D12S397.

Molecular Genetics

Using DNA samples from 11 Canadian Hutterite families with Bowen-Conradi syndrome, Armistead et al. (2009) analyzed 35 candidate genes within the 1.9-Mbp interval mapped by Lamont et al., 2005 and identified homozygosity for a missense mutation in the EMG1 gene (611531.0001) that segregated completely with disease. The mutation, which destroys an EcoRV site in the most highly conserved region of the protein, was not found in 414 non-Hutterite alleles.

Nomenclature

At the urging of Lowry (2004), the preferred title is listed as Bowen-Conradi syndrome. This title, as he pointed out, gives appropriate recognition to the first authors, indicates that the disorder occurs in non-Hutterites, and avoids a feeling of stigmatization on the part of the Hutterites.