Terminal Deletion Syndromes: Mechanisms, Detection & Classic Examples

Definition

A terminal deletion is loss of a chromosomal segment extending to the telomere. Size ranges from <100 kb (microdeletion) to entire chromosomal arms.

Mechanisms

• Meiotic unequal crossover
• Chromosome breakage (ionizing radiation, fragile sites)
• Replication fork collapse/repair errors
• Telomere attrition/crisis

Detection Methods

Method	Resolution	Best For
Karyotyping	~5–10 Mb	Large terminal deletions, translocations
FISH	~50–500 kb	Targeted confirmation (e.g., 5p, 4p, 22q11.2)
Chromosomal Microarray (CMA)	~10–50 kb	Genome-wide CNV detection, precise breakpoints
WES/WGS	Single exon/base	Breakpoint sequencing, cryptic rearrangements

Classic Terminal Deletion Syndromes

Syndrome	Locus	Cardinal Features
Cri du Chat	5p15.2-p15.3	High-pitched cat-like cry, microcephaly, ID, distinctive facies
Wolf-Hirschhorn	4p16.3	Growth restriction, ID, seizures, "Greek helmet" facies
Phelan-McDermid	22q13.3	Hypotonia, absent/limited speech, ASD, SHANK3 loss
1p36 Deletion	1p36.3	ID, seizures, cardiomyopathy, orofacial clefting

Somatic Terminal Deletions in Cancer

Acquired 17p (TP53), 13q14 (RB1), 11q22-23 (ATM) deletions drive tumorigenesis by unmasking tumor-suppressor loss.

Clinical Utility

Precise molecular diagnosis guides surveillance (cardiac, renal, oncologic), reproductive counseling, and targeted therapies.