How can a loss of chromosome X (q28-q28) not lead to a diagnosis of Turner syndrome?

Loss of Chromosome X (q28-q28) Without Turner Syndrome

A loss of chromosome X (q28-q28) may not lead to a diagnosis of Turner syndrome because Turner syndrome specifically requires complete or partial loss of an X chromosome affecting critical regions, while isolated deletions of specific segments like q28-q28 may not impact the genes responsible for the Turner syndrome phenotype.

Understanding Turner Syndrome Genetics

Turner syndrome is characterized by:

• Complete or partial loss of one X chromosome (45,X karyotype) in all or some cells
• Affects approximately 1 in 2,500 live female births 1
• Requires haploinsufficiency of specific genes, particularly those on the short arm (Xp) of the X chromosome 2

Key Genetic Considerations:

1. Critical Regions: The SHOX gene located on the short arm (Xp) is primarily responsible for the short stature phenotype in Turner syndrome 2

2. Mosaicism: Many patients with Turner syndrome have mosaicism (multiple cell lines with different chromosomal compositions) 3

3. Phenotypic Variability: The clinical presentation varies widely depending on:

   • The specific genetic regions affected
   • The percentage of cells with the chromosomal abnormality in mosaic cases 4

Why q28-q28 Deletion May Not Result in Turner Syndrome

1. Location of Deletion:

   • The q28-q28 region is on the long arm of the X chromosome
   • Turner syndrome features are primarily associated with short arm (Xp) deletions 2
   • Haploinsufficiency of the SHOX gene on Xp is responsible for short stature, a universal feature of classic Turner syndrome 5

2. Limited Gene Loss:

   • A small deletion in the q28-q28 region may not affect enough critical genes to produce the Turner syndrome phenotype
   • The precise genetic etiology of Turner syndrome involves multiple genes, not just a single region 2

3. Diagnostic Criteria:

   • Turner syndrome diagnosis requires both characteristic clinical features and cytogenetic findings
   • Without the typical phenotypic manifestations, a small X chromosome deletion would not meet diagnostic criteria 3

Clinical Implications of X Chromosome Deletions

Classic Turner Syndrome Features (often absent with isolated q28-q28 deletion):

• Short stature (nearly universal in 45,X karyotype) 4
• Primary amenorrhea (100% in classic 45,X) 4
• Cardiovascular abnormalities (bicuspid aortic valve in 10-25%, aortic coarctation in ~8%) 1
• Renal defects
• Recurrent otitis media
• Characteristic physical features (webbed neck, low hairline, etc.)

Phenotype-Karyotype Correlation:

• Patients with classical monosomy 45,X typically have more severe manifestations than those with other X chromosome abnormalities 4
• Patients with isochromosomes or partial deletions may have milder or atypical presentations 5

Clinical Significance

1. Cardiovascular Risk Assessment:

   • Turner syndrome patients have significantly increased risk of aortic dissection (36:100,000 person-years vs. 6:100,000 in general population) 1
   • Isolated q28-q28 deletion may not carry the same cardiovascular risks

2. Growth Considerations:

   • Patients with classic Turner syndrome benefit from early growth hormone treatment
   • Those with isolated q28-q28 deletions may not have the same growth impairment 5

3. Reproductive Implications:

   • Primary amenorrhea is universal in classic 45,X Turner syndrome
   • Secondary amenorrhea or preserved fertility may be seen in partial deletions 4

Diagnostic Approach for X Chromosome Abnormalities

1. Comprehensive Cytogenetic Analysis:

   • Karyotype analysis of multiple cells to detect mosaicism
   • Fluorescence in situ hybridization (FISH) for specific regions
   • Microarray testing as recommended by the American College of Medical Genetics 6

2. Phenotypic Assessment:

   • Evaluate for classic Turner syndrome features
   • Consider cardiovascular imaging if Turner syndrome is suspected 1

3. Genetic Counseling:

   • Explain the difference between isolated X chromosome deletions and Turner syndrome
   • Discuss potential health implications based on specific genes affected

Conclusion

The relationship between genotype and phenotype in X chromosome abnormalities is complex. A small deletion in the q28-q28 region of the X chromosome may not affect the critical genes responsible for the Turner syndrome phenotype, particularly those on the short arm like SHOX. Therefore, an individual with this specific deletion might not display the clinical features necessary for a Turner syndrome diagnosis.