Maternal SLE and brachytelephalangic chondrodysplasia punctata in a patient with unrelated de novo RAF1 and SIX2 variants

Abstract

Our improved tools to identify the aetiologies in patients with multiple abnormalities resulted in the finding that some patients have more than a single genetic condition and that some of the diagnoses made in the past are acquired rather than inherited. However, limited knowledge has been accumulated regarding the phenotypic outcome of the interaction between different genetic conditions identified in the same patients. We report a newborn girl with brachytelephalangic chondrodysplasia punctata (BCDP) as well as frontonasal dysplasia, ptosis, bilateral hearing loss, vertebral anomalies, and pulmonary hypoplasia who was found, by whole exome sequencing, to have a de novo pathogenic variant in RAF1 (c.770C>T, [p.Ser257Leu]) and a likely pathogenic variant in SIX2 (c.760G>A [p.A254T]), as well as maternal systemic lupus erythematosus (SLE). This case shows that BCDP is most probably not a diagnostic entity and can be associated with various conditions associated with CDP including maternal SLE.

Prevalence of Hearing Impairment Among Systemic Lupus Erythematosus Patients

“…Its incidence varies widely, with significant regional and ethnic disparities. For instance, the prevalence among Afro-Caribbean individuals in the UK spans a wide range, from as low as 0.3 per 100,000 to as high as 517.5 per million people (1,2). Studies in Asia have shown contrasting incidence rates in different countries.…”