Phenotypic variability in trisomy 13 mosaicism: Two new patients and literature review

Abstract

Trisomy 13 mosaicism occurs when two cell lines, one with a normal complement of chromosomes and the other with an additional chromosome 13, are present in the same individual. We present two children with trisomy 13 mosaicism and summarize the literature in 47 published cases. Our first patient is a 4-year-old male with normal development and dysmorphic features that include right microtia, tall forehead, bulbous nose, and high arched palate. The second patient died at 1 day of life secondary to laryngeal stenosis, a previously undocumented finding in trisomy 13. His other dysmorphic features included micrognathia, cleft soft palate, and an axillary pterygium. Several published case reports of patients with trisomy 13 mosaicism have had the typical phenotype of complete trisomy 13 with death in the neonatal period, while others have had few dysmorphic features and prolonged survival. The most common malformations in all 49 cases included ear anomalies, cleft lip and palate, and various congenital heart defects. Intelligence varied from normal in six patients to significant delays and mental retardation in the remainder of cases. There is no clear correlation between the percentage of trisomic cells and the level of intellectual function. The dysmorphic features seen vary considerably from one patient to the next, often making the clinical diagnosis of trisomy 13 mosaicism difficult. In counseling families, medical professionals should state that trisomy 13 mosaicism may lead to physical abnormalities and poor intellectual outcomes, but that the condition does not do so universally with normal development occurring in some individuals.

Monozygotic twins discordant for trisomy 13

“…Individuals with mosaicism for trisomy 13 can have a variable phenotype ranging from typical trisomy 13 syndrome to apparently normal phenotypes independent of the degree of mosaicism in peripheral blood or tissue. 15 The possibility for mosaicism will always exist for Twin B, regardless of the results of repeated genetic testing. Therefore, his growth and development will need to be monitored closely.…”

A girl with metopic synostosis and trisomy 13 mosaicism: Case report and review of the literature

“…In a review of 49 published cases with mosaic trisomy 13, the most common malformations were ear anomalies, cleft lip and palate, and congenital heart defects (CHDs) [Griffith et al, 2009]. Other features were seizures, polydactyly, micrognathia, and a short neck.…”

“…Mosaic trisomy 13 is very rare, it occurs in only 5% of all trisomy 13 cases [Magenis et al, 1968]. The spectrum of phenotypic variations in mosaic trisomy 13 cases is wide, some patients have the typical phenotype of complete trisomy 13 with neonatal death and others have few dysmorphic features and prolonged survival [Delatycki and Gardner, 1997;Griffith et al, 2009].…”

Positive cell-free fetal DNA testing for trisomy 13 reveals confined placental mosaicism

“…15,16 In addition, in cases in which trisomy 13 mosaicism is confirmed from amniocentesis, the outcome may be extremely variable and may range from normal to a characteristic trisomy 13 phenotype. 17,18 Complex and difficult counseling situations surrounding a prenatal diagnosis of mosaic trisomy 13 therefore arise. It is important to report such cases in the literature so that more information may be collected and made available to couples for counseling purposes.…”

“…1 This testing offers a noninvasive option for select aneuploidies by massively parallel shotgun sequencing of cffDNA present in a maternal blood sample. 1 By assigning each sequencing read to its respective chromosome, an overrepresentation of DNA fragments from a chromosome can be detected, indicating trisomies, most commonly for chromosomes 13,18, and 21. 1 Reported detection rates from laboratory validation studies are 99-100% and 97-100% for trisomy 21 and 18, respectively, with detection rates more variable for trisomy 13, ranging from 78 to 91%.…”