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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.

SUBMITTER: Alaqeel B

PROVIDER: S-EPMC6589797 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Coexistence of genetic conditions: exploring a possible relationship.

Alaqeel Bothainah B Babiker Amir A Al Mutairi Fuad F Al Dubayee Mohammed M

Sudanese journal of paediatrics 20190101 1

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, inc ...[more]

PMID: 31384091

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Project description:IntroductionKeratoconus (KC) is a complex, genetically heterogeneous, multifactorial degenerative disorder that is accompanied by corneal ectasia which usually progresses asymmetrically. With an incidence of approximately 1 per 2000 and 2 cases per 100,000 population presenting annually, KC follows an autosomal recessive or dominant pattern of inheritance and is, apparently, associated with genes that interact with environmental, genetic, and/or other factors. This is an important consideration in refractive surgery in the case of familial KC, given the association of KC with other genetic disorders and the imbalance between dizygotic twins. The present review attempts to identify the genetic loci contributing to the different KC clinical presentations and relate them to the common genetically determined comorbidities associated with KC.MethodsThe PubMed, MEDLINE, Google Scholar, and GeneCards databases were screened for KC-related articles published in English between January 2006 and November 2017. Keyword combinations of "keratoconus," "risk factor(s)," "genetics," "genes," "genetic association(s)," and "cornea" were used. In total, 217 articles were retrieved and analyzed, with greater weight placed on the more recent literature. Further bibliographic research based on the 217 articles revealed another 124 relevant articles that were included in this review. Using the reviewed literature, an attempt was made to correlate genes and genetic risk factors with KC characteristics and genetically related comorbidities associated with KC based on genome-wide association studies, family-based linkage analysis, and candidate-gene approaches.ResultsAn association matrix between known KC-related genes and KC symptoms and/or clinical signs together with an association matrix between identified KC genes and genetically related KC comorbidities/syndromes were constructed.ConclusionTwenty-four genes were identified as potential contributors to KC and 49 KC-related comorbidities/syndromes were found. More than 85% of the known KC-related genes are involved in glaucoma, Down syndrome, connective tissue disorders, endothelial dystrophy, posterior polymorphous corneal dystrophy, and cataract.

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Coexistence of genetic conditions: exploring a possible relationship.

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Coexistence of genetic conditions: exploring a possible relationship.

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