2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-A Case of Hexasomy 15q due to a Tricentric Supernumerary Chromosome 15

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This case study presents the medical history of a 7-month-old male who was admitted to the hospital for abnormal movements. Genetic testing revealed a complex structurally rearranged chromosome 15, resulting in partial hexasomy for 15q. The patient had a history of developmental delay, hypotonia, chronic cough/congestion, and was born with a limp, pale, and poor tone. He failed a newborn hearing screen and was later diagnosed with mixed hearing loss. At 11 months, he was noted to have developmental delay, hypotonia, and required bilateral hearing aids. Imaging studies, including MRI, echocardiogram, and renal ultrasound, were negative. Seizures are currently well-controlled with medication. The patient's weight is below the 3rd percentile and length is at the 25th percentile.<br /><br />Microarray testing revealed six copies of an ~7.6 Mb segment between common breakpoints BP1 and BP4, followed by four copies of an ~1.5 Mb segment between BP4 and BP5 in proximal 15q. Chromosome analysis confirmed a male karyotype with 47 chromosomes, including an extra tricentric chromosome. FISH analysis showed four copies of SNRPN in the additional derivative chromosome, indicating two inverted duplicated chromosome 15s linked together. Parental chromosomes were normal, confirming de novo inheritance.<br /><br />The rarity of individuals with a tricentric der(15), resulting in partial hexasomy 15q, was noted. Various techniques, including microarray, MLPA, FISH, and G-banding, were used to analyze the structure of the supernumerary marker chromosome 15. MLPA analysis confirmed the gain identified by cytogenetic studies and suggested maternal inheritance.<br /><br />Overall, this case study highlights a unique genetic abnormality that has resulted in developmental delay, hypotonia, hearing loss, and epilepsy in the patient. Further research and advanced technologies may be beneficial in understanding and resolving complex structural variants like this.

Asset Subtitle

Presenting Author - Emily G. Farrow, PhD, CGC; Co-Author - Laura Cross, MS, CGC; Co-Author - Bonnie R. Sullivan, MD; Co-Author - Keely Fitzgerald, DO; Co-Author - Ahmed T. Abdelmoity, MD, FAAP, FAES; Co-Author - Joseph T. Alaimo, PhD, FACMG; Co-Author - Elena A. Repnikova, PhD; Co-Author - John Herriges, PhD; Co-Author - Lei Zhang, PhD;

Meta Tag

array CGH

Chromosomal Abnormalities

Cytogenetics

FISH

Microarray

Co-Author Laura Cross, MS, CGC

Co-Author Bonnie R. Sullivan, MD

Co-Author Keely Fitzgerald, DO

Co-Author Ahmed T. Abdelmoity, MD, FAAP, FAES

Co-Author Joseph T. Alaimo, PhD, FACMG

Co-Author Elena A. Repnikova, PhD

Co-Author John Herriges, PhD

Co-Author Lei Zhang, PhD

Presenting Author Emily G. Farrow, PhD, CGC

Keywords

medical history

7-month-old male

abnormal movements

genetic testing

chromosome 15

partial hexasomy

developmental delay

hypotonia

mixed hearing loss

seizures