2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Chromosome 6 maternal uniparental isodisomy in a child with global developmental delay

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This document discusses a case of chromosome 6 maternal uniparental disomy (UPD6mat) in a child with global developmental delay. UPD is a condition where both copies of a chromosome are inherited from one parent. It can occur due to non-disjunction error in meiosis II followed by trisomy rescue or a monosomy conception followed by mitotic monosomy rescue. UPD can have clinical consequences such as unmasking of recessive disease genes, imprinting disorders, and somatic mosaicism.<br /><br />The patient in this case is a 20-month-old girl with a history of preterm delivery, intrauterine growth retardation (IUGR), feeding and nutritional issues, cardiac murmur, ambiguous genitalia, and developmental delay. She was diagnosed with congenital adrenal hyperplasia (CAH) and microarray analysis revealed a single large region of homozygosity (ROH) spanning chromosome 6.<br /><br />The phenotype of chromosome 6 maternal UPD is not well-defined, but previous cases have shown a higher prevalence of IUGR and preterm delivery. Maternal UPD6 can also result in Transient Neonatal Diabetes Mellitus. However, developmental delay has not been commonly associated with maternal UPD6.<br /><br />In conclusion, this case suggests that UPD6mat may be the cause of the patient's preterm delivery and IUGR. Developmental delay may also be an additional feature of UPD6. Further research and genetic testing are needed to better understand the clinical consequences and phenotypic variations of UPD6mat.<br /><br />References:<br /><br />1. Nakka P, Smith S P, O’Donnell-Luria A H, McManus K F, et al. 2019. Characterization of prevalence and health consequences of uniparental disomy in Four Million Individuals from the General Population.<br /><br />2. Kerr, E.R., Stuhlmiller, G.M., Maha, G.C. et al. 2018. Maternal uniparental isodisomy for chromosome 6 discovered by paternity testing: a case report.<br /><br />3. Eggermann T, Oehl-Jaschkowitz B, Dicks S, Thomas W, Kanber D, et al. 2017. The maternal uniparental disomy of chromosome 6 (upd(6)mat) "phenotype": result of placental trisomy 6 mosaicism?<br /><br />4. Lazier J, Martin N, Stavropoulos J D, and Chitayat D. 2016. Maternal uniparental disomy for chromosome 6 in a patient with IUGR, ambiguous genitalia, and persistent mullerian structures.<br /><br />5. Leung W C., Lau W. L., Lo T. K., Lau T. K., Lam Y. Y., Kan A. et al. 2016. Two IUGR fetuses with maternal uniparental disomy of chromosome 6 or UPD(6)mat.<br /><br />6. Scheuvens, R., Begemann M., Soellner L., Meschede D., Raabe‐Meyer G., Elbracht M., et al. 2016. Maternal uniparental disomy of chromosome 16 (upd(16)mat): Clinical features are rather caused by (hidden) trisomy 16 mosaicism than by upd(16)mat itself.<br /><br />7. Soellner, L., Begemann M., Mackay D. J., Grønskov K., Tümer Z., Maher E. R., et al. 2017. Recent advances in imprinting disorders.

Asset Subtitle

Presenting Author - Nyolima N. Kapalanga, MD, PhD, FACMG; Co-Author - Lydia Reynolds Royer, MD;

Meta Tag

array CGH

Chromosomal Abnormalities

Cytogenetics

Imprinting

Microarray

Pathogenesis

Phenotype

Co-Author Lydia Reynolds Royer, MD

Presenting Author Nyolima N. Kapalanga, MD, PhD, FACMG

Keywords

chromosome 6 maternal uniparental disomy

global developmental delay

non-disjunction error

meiosis II

trisomy rescue

monosomy conception

mitotic monosomy rescue

recessive disease genes

imprinting disorders

somatic mosaicism