Diagnosis and clinical delineation of mosaic tetrasomy 5p

Eur J Med Genet. 2020 Jan;63(1):103634. doi: 10.1016/j.ejmg.2019.02.006. Epub 2019 Feb 21.


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: 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: 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: 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: 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.

Keywords: 5p mosaicism; Confined placental mosaicism; Genetic counseling; Isochromosome; Tetrasomy 5p.

Publication types

  • Review

MeSH terms

  • Abnormalities, Multiple / diagnosis*
  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / pathology
  • Adult
  • Amniocentesis / methods
  • Child
  • Chromosome Disorders / diagnosis
  • Chromosome Disorders / genetics
  • Chromosomes, Human, Pair 5 / genetics
  • Developmental Disabilities / diagnosis*
  • Developmental Disabilities / genetics
  • Developmental Disabilities / pathology
  • Female
  • Genetic Testing
  • Humans
  • In Situ Hybridization, Fluorescence
  • Isochromosomes / genetics
  • Karyotyping
  • Male
  • Mosaicism*
  • Pregnancy
  • Prenatal Diagnosis
  • Tetrasomy / diagnosis*
  • Tetrasomy / genetics
  • Tetrasomy / pathology