The Journal of pediatrics · 2023
Exome Sequencing Identifies Multiple Genetic Diagnoses in Children with Syndromic Growth Disorders.
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Rezende Raissa Carneiro, Menezes de Andrade Nathalia Liberatoscioli, Branco Dantas Naiara Castelo, de Polli Cellin Laurana, Victorino Krepischi Ana Cristina, Lerario Antonio Marcondes, de Lima Jorge Alexander Augusto
Аннотация
OBJECTIVE: To evaluate the presence of multiple genetic diagnoses in syndromic growth disorders.
STUDY DESIGN: We carried out a cross-sectional study to evaluate 115 patients with syndromic tall (n = 24) or short stature (n = 91) of unknown cause from a tertiary referral center for growth disorders. Exome sequencing was performed to assess germline single nucleotide, InDel, and copy number variants. All variants were classified according to ACMG/AMP guidelines. The main outcome measured was the frequency of multiple genetic diagnoses in a cohort of children with syndromic growth disorders.
RESULTS: The total diagnostic yield of the cohort was 54.8% (63/115). Six patients had multiple genetic diagnoses (tall stature group = 2; short stature group = 4). The proportion of multiple diagnoses within total cases was 5.2% (6/115), and within solved cases was 9.5% (6/63). No characteristics were significantly more frequent when compared with patients with single or multiple genetic findings. Among patients with multiple diagnoses, 3 had syndromes with overlapping clinical features, and the others had syndromes with distinct phenotypes.
CONCLUSION: Recognition of multiple genetic diagnoses as a possibility in complex cases of syndromic growth disorders opens a new perspective on treatment and genetic counseling for affected patients, defying the medical common sense of trying to fit all findings into one diagnosis.
STUDY DESIGN: We carried out a cross-sectional study to evaluate 115 patients with syndromic tall (n = 24) or short stature (n = 91) of unknown cause from a tertiary referral center for growth disorders. Exome sequencing was performed to assess germline single nucleotide, InDel, and copy number variants. All variants were classified according to ACMG/AMP guidelines. The main outcome measured was the frequency of multiple genetic diagnoses in a cohort of children with syndromic growth disorders.
RESULTS: The total diagnostic yield of the cohort was 54.8% (63/115). Six patients had multiple genetic diagnoses (tall stature group = 2; short stature group = 4). The proportion of multiple diagnoses within total cases was 5.2% (6/115), and within solved cases was 9.5% (6/63). No characteristics were significantly more frequent when compared with patients with single or multiple genetic findings. Among patients with multiple diagnoses, 3 had syndromes with overlapping clinical features, and the others had syndromes with distinct phenotypes.
CONCLUSION: Recognition of multiple genetic diagnoses as a possibility in complex cases of syndromic growth disorders opens a new perspective on treatment and genetic counseling for affected patients, defying the medical common sense of trying to fit all findings into one diagnosis.