Diagnosis and clinical delineation of mosaic tetrasomy 5p.


Journal

European journal of medical genetics
ISSN: 1878-0849
Titre abrégé: Eur J Med Genet
Pays: Netherlands
ID NLM: 101247089

Informations de publication

Date de publication:
Jan 2020
Historique:
received: 12 01 2019
revised: 06 02 2019
accepted: 17 02 2019
pubmed: 25 2 2019
medline: 2 10 2020
entrez: 25 2 2019
Statut: ppublish

Résumé

Our objective was to review the phenotypic and genetic characteristics of tetrasomy 5p from the fetal period until adulthood including prenatal diagnostic evaluations. Tetrasomy 5p is a rare chromosomal abnormality. Of the 14 reports, most document mosaic tetrasomy 5p resulting from a supernumerary marker chromosome or isochromosome. There is a wide range of phenotypic manifestations with severity related to more proximal breakpoints and the degree of mosaicism. We conducted a systematic review using Scopus, PubMed Central® and Ovid MEDLINE® from inception through July 1, 2018 for all articles describing tetrasomy 5p. All articles describing the syndrome of tetrasomy 5p were included. Of the 15 included cases, 13 exhibited mosaic tetrasomy and two had complete tetrasomy identified by amniocentesis. The most common features include seizures (8/11 live births, 73%), hypotonia (7/11 live births, 64%), developmental delay (7/9 cases that reached childhood, 78%), abnormal external ears (6/11 live births, 55%), short stature (6/11 live births, 55%), ventriculomegaly (5/11 live births, 45.5%) and congenital heart defect (6/15 cases, 40%). The clinical phenotype ranged in severity from mild with no defining characteristics to severe with seizures, developmental delay, and multiple congenital anomalies, resulting in early death. Of these 15 cases, only 6 were diagnosed prenatally by prenatal genetic testing (40%) with prenatal ultrasound identifying abnormalities in 4/6 (67%). Confined placental mosaicism (CPM) was diagnosed in six additional cases due to discordance between CVS and amniocentesis results. Four of the five live births returned for evaluation and each showed normal development. Fourteen out of 15 (93%) cases of tetrasomy 5p were associated with an abnormal phenotype. Once a diagnosis is made prenatally, a detailed anatomy ultrasound and fetal echocardiogram must be performed to further characterize any structural abnormalities of the fetus and potentially estimate the clinical severity. Caution should be exercised when prenatal diagnosis of mosaic tetrasomy 5p is found by chorionic villus sampling. CVS alone is insufficient to diagnose tetrasomy 5p and needs to be confirmed with amniocentesis. Our review seeks to inform clinicians on the current literature regarding tetrasomy 5p so that they may better counsel patients when this syndrome is diagnosed.

Sections du résumé

OBJECTIVE OBJECTIVE
Our objective was to review the phenotypic and genetic characteristics of tetrasomy 5p from the fetal period until adulthood including prenatal diagnostic evaluations.
BACKGROUND BACKGROUND
Tetrasomy 5p is a rare chromosomal abnormality. Of the 14 reports, most document mosaic tetrasomy 5p resulting from a supernumerary marker chromosome or isochromosome. There is a wide range of phenotypic manifestations with severity related to more proximal breakpoints and the degree of mosaicism.
DESIGN METHODS
We conducted a systematic review using Scopus, PubMed Central® and Ovid MEDLINE® from inception through July 1, 2018 for all articles describing tetrasomy 5p. All articles describing the syndrome of tetrasomy 5p were included.
RESULTS RESULTS
Of the 15 included cases, 13 exhibited mosaic tetrasomy and two had complete tetrasomy identified by amniocentesis. The most common features include seizures (8/11 live births, 73%), hypotonia (7/11 live births, 64%), developmental delay (7/9 cases that reached childhood, 78%), abnormal external ears (6/11 live births, 55%), short stature (6/11 live births, 55%), ventriculomegaly (5/11 live births, 45.5%) and congenital heart defect (6/15 cases, 40%). The clinical phenotype ranged in severity from mild with no defining characteristics to severe with seizures, developmental delay, and multiple congenital anomalies, resulting in early death. Of these 15 cases, only 6 were diagnosed prenatally by prenatal genetic testing (40%) with prenatal ultrasound identifying abnormalities in 4/6 (67%). Confined placental mosaicism (CPM) was diagnosed in six additional cases due to discordance between CVS and amniocentesis results. Four of the five live births returned for evaluation and each showed normal development.
CONCLUSIONS CONCLUSIONS
Fourteen out of 15 (93%) cases of tetrasomy 5p were associated with an abnormal phenotype. Once a diagnosis is made prenatally, a detailed anatomy ultrasound and fetal echocardiogram must be performed to further characterize any structural abnormalities of the fetus and potentially estimate the clinical severity. Caution should be exercised when prenatal diagnosis of mosaic tetrasomy 5p is found by chorionic villus sampling. CVS alone is insufficient to diagnose tetrasomy 5p and needs to be confirmed with amniocentesis. Our review seeks to inform clinicians on the current literature regarding tetrasomy 5p so that they may better counsel patients when this syndrome is diagnosed.

Identifiants

pubmed: 30797979
pii: S1769-7212(19)30032-1
doi: 10.1016/j.ejmg.2019.02.006
pii:
doi:

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

103634

Informations de copyright

Copyright © 2019 Elsevier Masson SAS. All rights reserved.

Auteurs

Sophia Blakey-Cheung (S)

1025 Walnut Street #100, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, 19107, USA.

Pamela Parker (P)

833 Chestnut Street, Department of Obstetrics and Gynecology, Thomas Jefferson University Hospital, Philadelphia, PA, 19107, USA.

William Schlaff (W)

833 Chestnut Street, Department of Obstetrics and Gynecology, Thomas Jefferson University Hospital, Philadelphia, PA, 19107, USA.

Brent Monseur (B)

833 Chestnut Street, Department of Obstetrics and Gynecology, Thomas Jefferson University Hospital, Philadelphia, PA, 19107, USA.

Kim Keppler-Noreuil (K)

5140 South Drive, Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Huda B Al-Kouatly (HB)

833 Chestnut Street, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, U19107, USA. Electronic address: Huda.Al-Kouatly@jefferson.edu.

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Classifications MeSH