Trisomy D

Trisomy D is an older cytogenetic term that historically referred to a group of chromosomal abnormalities involving an extra chromosome from the “D group” of human chromosomes. In modern genetic nomenclature, Trisomy D specifically corresponds to Trisomy 13, also known as Patau Syndrome. This genetic disorder results from the presence of an extra copy of chromosome 13, leading to multiple congenital anomalies and severe developmental impairments.

Historical Context and Nomenclature

Before the modern system of numbering chromosomes (1–22 and sex chromosomes), human chromosomes were classified into seven groups (A–G) based on their size and centromere position. The D group included chromosomes 13, 14, and 15.
When the condition now known as Trisomy 13 was first described cytogenetically in the early 1960s, it was referred to as Trisomy D, meaning an individual possessed three copies of one of the D-group chromosomes. With advancements in chromosome identification techniques, it was later determined that the extra chromosome involved was chromosome 13.
Hence, Trisomy D and Trisomy 13 (Patau Syndrome) are synonymous terms in contemporary medical genetics.

Genetic Basis

Trisomy 13 occurs when a person has three copies of chromosome 13 instead of the normal two. This extra genetic material disrupts normal development, leading to multiple organ system abnormalities. The extra chromosome can arise due to several mechanisms:

1. Full Trisomy 13: Every cell in the body contains an extra chromosome 13. This is the most common form, resulting from nondisjunction during meiosis.
2. Mosaic Trisomy 13: Some cells have an extra chromosome 13, while others are normal, leading to a milder phenotype.
3. Translocation Trisomy 13: Part of chromosome 13 becomes attached to another chromosome, usually chromosomes 14 or 15. This can be inherited from a balanced carrier parent.

The condition is not typically inherited in its full form but results from random errors during the formation of reproductive cells.

Epidemiology

Trisomy 13 is one of the rarest viable autosomal trisomies, occurring in approximately 1 in 10,000 to 1 in 16,000 live births. It affects both males and females equally. The risk of occurrence increases with maternal age, as the likelihood of chromosomal nondisjunction rises with advancing age.

Clinical Features

Trisomy 13 (Trisomy D) affects multiple organ systems, leading to a characteristic set of physical and neurological abnormalities. Common features include:

• Craniofacial anomalies:
  • Cleft lip and/or palate
  • Microphthalmia (abnormally small eyes)
  • Anophthalmia (absence of one or both eyes)
  • Low-set ears and scalp defects
• Central nervous system defects:
  • Holoprosencephaly (failure of the brain to divide into two hemispheres)
  • Severe intellectual disability
  • Seizures
• Cardiac abnormalities:
  • Ventricular septal defect (VSD)
  • Atrial septal defect (ASD)
  • Patent ductus arteriosus (PDA)
• Musculoskeletal and limb anomalies:
  • Polydactyly (extra fingers or toes)
  • Rocker-bottom feet
  • Clenched hands with overlapping fingers
• Genitourinary and gastrointestinal defects:
  • Kidney malformations
  • Omphalocele or abdominal wall defects
• Growth and development:
  • Low birth weight
  • Failure to thrive
  • Severe psychomotor delay

Because of the extensive organ involvement, affected infants often have significant medical complications from birth.

Diagnosis

Diagnosis of Trisomy 13 can occur prenatally or after birth through several methods:

• Prenatal Screening: Maternal serum screening and ultrasonography can identify features suggestive of chromosomal abnormalities, such as holoprosencephaly or heart defects.
• Non-Invasive Prenatal Testing (NIPT): Analyses cell-free foetal DNA in maternal blood for the presence of extra chromosome 13 material.
• Confirmatory Diagnosis:
  • Karyotyping confirms the presence of an additional chromosome 13.
  • Fluorescence in situ hybridisation (FISH) or chromosomal microarray analysis (CMA) may be used for rapid or detailed confirmation.

Prognosis and Life Expectancy

Trisomy 13 is associated with a very poor prognosis. Many affected foetuses do not survive to term, and among live-born infants, over 80–90% die within the first year of life, most commonly due to heart or respiratory failure.
However, survival beyond infancy, though rare, has been reported, especially in cases of mosaic or partial trisomy 13. Those who survive experience profound developmental delays and multiple disabilities.

Management and Treatment

There is no cure for Trisomy 13; management focuses on supportive and palliative care to improve comfort and quality of life. Treatment typically includes:

• Medical management of complications: Addressing heart defects, feeding difficulties, and respiratory problems.
• Surgical interventions: For correctable anomalies such as cleft palate or congenital heart defects (if compatible with life).
• Supportive therapies: Physiotherapy, occupational therapy, and developmental support for surviving infants.
• Genetic counselling: Essential for affected families, particularly if a parent is a carrier of a chromosomal translocation involving chromosome 13.

Genetic Counselling and Prevention

Couples with a history of Trisomy 13 or recurrent pregnancy loss are advised to undergo chromosomal analysis and genetic counselling. Prenatal testing options, such as chorionic villus sampling (CVS) or amniocentesis, help detect the condition in early pregnancy.
Parents of children with translocation trisomy 13 have an increased risk of recurrence in future pregnancies, while those with nondisjunction forms have a low recurrence risk.