An autosomal recessive transmitted disease resulting in death in the first year of life secondary to neurologic disease and airway problems.
First described by the Canadian physicians P. Bowen and G. J. Conradi in 1976 in two brothers whose parents were second cousins Hutterite. Three years later, A. G. W. Hunter and colleagues, also Canadian physicians, described six more Hutterite children form five families.
Approximately 60 cases have been reported in the literature. The vast majority of them are Hutterite children and only a small proportion is from other populations. The estimated incidence in the Hutterite population is 1:355 live births.
Autosomal recessive trait. Comprehensive pedigree records have enabled researchers to determine that all six of the initially reported Hutterite families are related to a kindred extending back to the 1770s. The Hutterites subdivided into three endogamous subdivisions called leut groups (the Schmiedeleut, the Lehrerleut, and the Dariusleut) after arriving in North America in the late 1800s. Cases recognized from colonies in northern and southern Alberta, South Dakota, and southern Manitoba suggest the mutation for this condition is widely distributed among this population predicting a carrier frequency of 1 in 10. The gene locus of BCS has been mapped to 12p13.3. The EMG1 gene (Essential for Mitotic Growth 1; also known as NEP1 gene [Nucleolar Essential Protein 1] in Yeast), encodes an enzyme (N1-specific pseudouridine methyltransferase) that is required for the biosynthesis of the small ribosomal subunits (SSU). The genetic defect in BCS is caused by a single point aspartate 86 to glycine mutation in EMG1 affecting the RNA methyltransferase. The mutated enzyme is destabilized and mislocalizes to the nucleoplasm where it accumulates. Animal models suggest that the defect in BCS may lead to nucelolar dysfunction with a generalized decrease in cell proliferation, which is particularly pronounced in the central nervous system. The parents of these patients show no clinical features of the disorder.
BCS is now recognized as ribosomopathy.
Based on the clinical course, physical appearance and family history. BCS is morphologically very similar to ☞Trisomy 18, however, the karyotype is normal in the former.
These children are usually born at term, but about half of them are small for gestational age and delivered from a breech presentation. The major features consist of proportional prenatal and postnatal growth retardation with low birth weight, micro- and dolichocephaly, sloping forehead with absent nasofrontal angle, prominent nose and nasal bridge, severe micrognathia, retroglossia, microstomia, high-arched palate, narrow pharynx, and short neck. Skeletal anomalies may include vertical tali (rocker-bottom feet), flexion contractures of some of the large joints (hips, knees), and the ...