2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-A Rare Combination: Novel Presentation of Achondroplasia with a Complex Chromosomal Rearrangement

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This document describes a rare case of a patient with a complex combination of achondroplasia and a chromosomal rearrangement. Achondroplasia is a common skeletal disorder that causes disproportionate short stature. It is typically diagnosed based on clinical and radiological features and is caused by spontaneous mutations in the FGFR3 gene. Chromosomal translocations are relatively common and usually do not cause adverse effects. However, there is a risk of gain or loss of genomic material at the translocation breakpoints.<br /><br />The patient in this case is a 7-year-old girl with short stature, macrocephaly (larger than average head size), dysmorphic features, and developmental delays. She was born prematurely with short long bones identified on an ultrasound. She also had neonatal seizures, but MRI results were normal. Genetic testing revealed a chromosomal rearrangement involving chromosomes 1 and 7, with multiple interstitial deletions.<br /><br />The patient was initially suspected to have achondroplasia, but her head growth, seizure history, and developmental delays were not consistent with the condition. Further genetic testing confirmed that she had the common FGFR3 mutation associated with achondroplasia. Repeat skeletal surveys showed shortened long bones, metaphyseal irregularities, and other characteristic features of achondroplasia.<br /><br />The chromosomal rearrangement in this patient affected multiple genes, which likely contributed to her neurological and developmental issues. The deleted regions on chromosome 7 are associated with neurodevelopmental delays, cognitive disability, and seizure disorders. Other candidate genes may also play a role in her atypical growth.<br /><br />This case highlights the challenges in diagnosing and managing patients with complex combinations of genetic disorders. The presence of a chromosomal rearrangement can complicate the diagnosis of achondroplasia and require additional genetic testing. Further research is needed to fully understand the clinical impact of these complex genetic conditions.

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Presenting Author - Travis Schreier, MD; Co-Author - Joanna Spaulding, M.S.; Co-Author - Bhavana J. Dave, PhD; Co-Author - Danita Velasco, MD;

Meta Tag

Bone/Joint Abnormalities

Chromosomal Abnormalities

Genetic Testing

Musculoskeletal system

Co-Author Joanna Spaulding, M.S.

Co-Author Bhavana J. Dave, PhD

Co-Author Danita Velasco, MD

Presenting Author Travis Schreier, MD

Keywords

achondroplasia

chromosomal rearrangement

skeletal disorder

short stature

FGFR3 gene

chromosomal translocations

genomic material

macrocephaly

dysmorphic features

developmental delays