Coexistence of genetic conditions: Exploring a possible relationship

Abstract

We report on a 3-year-old boy who has congenital adrenal hyperplasia and a suspected Van Maldergem syndrome, another genetic condition, with the classic phenotype seen in our patient. The latter diagnosis was supported by a genetic test that showed a novel and likely pathogenic variant in a previously described gene of the syndrome. Paediatricians do encounter such a challenge of coexisting genetic conditions albeit infrequently, and advanced genetic analysis, example whole exome sequencing, increasingly report variants of unknown significance with a variable degree of potential pathogenicity. The treating physician needs to follow a systematic approach and entertain thorough literature search and brainstorming in order to prove or disprove any possible relationship between coexisting genetic conditions. The first step should be confirming the existence of the two conditions in the first place. In addition, when family segregation is unable to confidently make a sensible conclusion in such cases, a clinician should proceed to advanced functional studies to confirm pathogenicity. Then, one can explore further any hidden relationship between coexisting and possibly clinically-related genetic conditions.

The odyssey of diagnosing genetic disorders in evolving health services

“…Rare ID syndromes and children with non-syndromic ID constitute a diagnostic challenge and require extensive clinical, laboratory and radiological evaluations; and many of these procedures are invasive and costly. To overcome these challenges, the evolving health services in this Region are rapidly implementing the recently available high throughput genomic sequencing techniques, as shown in the third article on genetics in the current SJP issue [13]. It emphasises the advantage of multi-locus analysis provided by next-generation sequencing over conventional single-gene investigations in uncovering dual molecular diagnoses in patients with phenotype pointing to two clinical diagnoses involving two separate genetic loci.…”