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.

With only 11 patients reported, 5p tetrasomy belongs to rare postnatal findings. Most cases are due to small supernumerary marker chromosomes (sSMCs) or isochromosomes. The patients share common but unspecific symptoms such as developmental delay, seizures, ventriculomegaly, hypotonia, and fifth finger clinodactyly. Simple interstitial duplications leading to trisomies of parts of 5p are much more frequent and better described. Duplications encompassing 5p13.2 cause a defined syndrome with macrocephaly, distinct facial phenotype, heart defects, talipes equinovarus, feeding difficulties, respiratory distress and anomalies of the central nervous system, developmental delay and hypotonia. We present a boy with dysmorphic features, developmental delay, intellectual disability and congenital anomalies, and a mosaic sSMC inv dup(5)(p15.33p15.1). He is the fourth and the oldest reported patient with distal 5p tetrasomy. His level of mosaicism was significantly different in lymphocytes (13.2%) and buccal cells (64.7%). The amplification in our patient is smaller than that in the three previously published patients but the only phenotype difference is the absence of seizures in our patient. Our observations indicate that for the assessment of prognosis, especially with respect to intellectual functioning, the level of mosaicism could be more important than the extent of amplification and the number of extra copies. Evaluation of the phenotypical effect of rare chromosomal aberrations is challenging and each additional case is valuable for refinement of the genotype-phenotype correlation. Moreover, our patient demonstrates that if the phenotype is severe and if the level of sSMC mosaicism is low in lymphocytes, other tissues should be tested.