Tuesday, December 17, 2013

Diagnosis .....


Clinical Diagnosis


Tetra Amelia Syndrome [TAS] is characterized by the complete absence of all four limbs (Figure 1). The diagnosis of Tetra Amelia Syndrome can be established clinically and is usually made on routine Prenatal Ultrasonography (Figure 2).

Figure 1

Figure 1. Postmortem radiograph of fetus with tetra-amelia syndrome demonstrating absence of all four limbs (without defects of scapulae and clavicles)

Figure 2

Figure 2. Prenatal ultrasonography showing fetus without limbs

Testing

Cytogenetic analyses, performed in some of the reported cases, showed normal karyotypes without ‘premature centromere separation’ (Roberts syndrome: www.ncbi.nlm.nih.gov/books/NBK1153).

Molecular Genetic Testing

Gene: WNT3 is the only gene in which mutations are known to cause Tetra Amelia Syndrome [TAS] in one family [Niemann et al 2004].

Evidence for Locus Heterogeneity: Genetic heterogeneity of Tetra Amelia Syndrome [TAS] is strongly suggested by Krahn et al [2005]& Sousa et al [2008], who described fetuses with tetra-amelia, agenesis of both lungs, cleft lip/cleft palate and micrognathia in whom no mutations were identified in the coding exon regions of WNT3 and other candidate genes.

Clinical Testing

Summary of Molecular Genetic Testing Used in Tetra-Amelia Syndrome

Gene Symbol
Test Method
Mutations Detected
Mutation Detection Frequency by Test Method 1
Test Availability
WNT3
Sequence analysis
p.Gln83X
(c.247C>T) 2
Unknown 3
Clinical
Deletion/ Duplication Analysis 4
Deletion/Duplication of one or more ‘exons’ or the whole gene
Unknown
none reported 5

1. The ability of the test method used to detect a mutation that is present in the indicated gene
2. Only one family studied to date [Niemann et al 2004]
3. Percentage of detectable mutations is unknown, as a WNT3 mutation has so far been demonstrated in only one family with tetra-amelia syndrome [Niemann et al 2004].
4. Testing that identifies deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), andchromosomal microarray (CMA) that includes this gene/chromosome segment.

5. No deletions or duplications of WNT3 have been reported to cause tetra-amelia syndrome. (Note: By definition, deletion/duplication analysis identifies rearrangements that are not identifiable by sequence analysis of genomic DNA.)




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