Coexistence of Genetic Diseases Is a New Clinical Challenge: Three Unrelated Cases of Dual Diagnosis

Genes (Basel). 2023 Feb 14;14(2):484. doi: 10.3390/genes14020484.


Technological advancements in molecular genetics and cytogenetics have led to the diagnostic definition of complex or atypical clinical pictures. In this paper, a genetic analysis identifies multimorbidities, one due to either a copy number variant or a chromosome aneuploidy, and a second due to biallelic sequence variants in a gene associated with an autosomal recessive disorder. We diagnosed the simultaneous presence of these conditions, which co-occurred by chance, in three unrelated patients: a 10q11.22q11.23 microduplication and a homozygous variant, c.3470A>G (p.Tyr1157Cys), in the WDR19 gene associated with autosomal recessive ciliopathy; down syndrome and two variants, c.850G>A; p.(Gly284Arg) and c.5374G>T; p.(Glu1792*), in the LAMA2 gene associated with merosin-deficient congenital muscular dystrophy type 1A (MDC1A); and a de novo 16p11.2 microdeletion syndrome and homozygous variant, c.2828G>A (p.Arg943Gln), in the ABCA4 gene associated with Stargardt disease 1 (STGD1). The possibility of being affected by two relatively common or rare inherited genetic conditions would be suspected when signs and symptoms are incoherent with the primary diagnosis. All this could have important implications for improving genetic counseling, determining the correct prognosis, and, consequently, organizing the best long-term follow-up.

Keywords: clinical competence; diagnosis; genetic diseases; phenotype; rare diseases.

Publication types

  • Case Reports

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Diagnosis, Dual (Psychiatry)
  • Homozygote
  • Humans
  • Muscular Dystrophies* / genetics
  • Stargardt Disease
  • Substance-Related Disorders*


  • ABCA4 protein, human
  • ATP-Binding Cassette Transporters

Supplementary concepts

  • Muscular dystrophy congenital, merosin negative

Grants and funding

This research received no external funding.