Diploid-triploid mosaicism

Overview

Diploid-triploid mosaicism is a rare chromosomal disorder in which an individual has two distinct cell lines: one with the normal diploid set of chromosomes (46 chromosomes) and another with a triploid set (69 chromosomes). This mosaic pattern arises due to errors during early embryonic development. The condition leads to a highly variable set of physical and developmental abnormalities depending on the proportion and distribution of triploid cells in different tissues.

Causes

Diploid-triploid mosaicism occurs due to a genetic error during fertilization or early cell division in the embryo. The most common mechanisms include:

• Dispermy: Fertilization of one egg by two sperm, followed by partial correction resulting in both diploid and triploid cells.

• Mitotic error: An error in chromosome division during early embryonic mitosis that leads to some cells developing with 69 chromosomes.

The condition is not inherited and occurs sporadically. The severity of symptoms depends on how widely the triploid cells are distributed in the body.

Symptoms

The symptoms of diploid-triploid mosaicism are highly variable and may include a combination of the following features:

• Growth retardation: Both prenatal and postnatal growth delays are common.

• Hypotonia: Reduced muscle tone and strength in infancy.

• Developmental delay: Intellectual disability, delayed milestones, and learning difficulties.

• Facial dysmorphism: Including a broad forehead, wide-set eyes, low-set ears, and a small jaw.

• Skin pigmentary anomalies: Areas of hyperpigmentation or hypopigmentation following Blaschko’s lines.

• Limb asymmetry or abnormalities: Uneven limb growth or finger/toe anomalies.

• Organ malformations: Such as heart defects, kidney anomalies, or genital abnormalities.

Not all individuals will exhibit all these symptoms, and the presentation can vary from mild to severe.

Diagnosis

Diagnosis of diploid-triploid mosaicism can be challenging due to the variability in clinical presentation and the potential for mosaicism to be missed if triploid cells are not present in the sampled tissue. Diagnostic methods include:

• Karyotyping: Chromosome analysis of blood, skin, or other tissues to detect the presence of both diploid and triploid cell lines.

• Chromosomal microarray or FISH: More sensitive techniques to detect mosaic patterns in low-percentage triploid cell lines.

• Prenatal testing: May be identified through chorionic villus sampling (CVS) or amniocentesis, although confirmation postnatally is often necessary.

Treatment

There is no cure for diploid-triploid mosaicism. Treatment focuses on managing the specific symptoms and developmental issues present in each individual. A multidisciplinary approach is typically required and may include:

• Early intervention programs: Including physical, occupational, and speech therapy.

• Special education services: Tailored to the child's developmental and cognitive needs.

• Surgical interventions: May be necessary for structural abnormalities such as heart defects or limb differences.

• Regular monitoring: For growth, neurological development, and organ function.

• Genetic counseling: For families to understand the condition and its implications.

Prognosis

The prognosis for individuals with diploid-triploid mosaicism varies widely and depends on the degree of mosaicism, the organs involved, and the severity of physical and developmental abnormalities. Some individuals may survive into childhood or adulthood with varying degrees of disability, while others may experience life-threatening complications in infancy. With supportive care and appropriate interventions, many children with this condition can achieve improved developmental outcomes and quality of life.