Abstract
Introduction: Blended phenotypes resulting from the contribution of two or more genetic variants to the disease of a patient pose a significant diagnostic challenge. Correlating between the phenotypes and the genotypes of the affected patients is difficult in these cases, especially in the absence of a large family segregating the condition. Case Presentation: We report a child born to consanguineous Syrian parents with a complex phenotype including a skeletal dysplasia, characterized by a small thorax and phalangeal shortening, as well as cardiac anomalies and sensorineural hearing loss. Molecular analysis identified the presence of three potentially disease-causing genetic variants. These include homozygous variants in the IHH and TTC12B genes, known to be associated with acrocapitofemoral dysplasia (OMIM# 607778) and a form of short-rib thoracic dysplasia (OMIM# 613819), respectively, in addition to a heterozygous variant in the COL11A1 gene, associated with dominant forms of skeletal dysplasia, such as Marshall (OMIM# 154780) and Stickler (OMIM# 608481) syndromes, and hearing loss (OMIM# 618533). Conclusion: We propose that the complex phenotype observed in the patient results from the contribution of l three of these variants. This case highlights some of the challenges encountered in the genetic counseling of families with rare genetic conditions.
Journal Section:
Novel Insights from Clinical Practice
Keywords:
Cardiopathy,
Chondrodysplasia,
Ciliopathy,
COL11A1,
Exome sequencing,
Hearing loss,
IHH,
Skeletal dysplasia,
TTC12B
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