Genetic investigations

 Karyotyping ('chromosomes', G-banding)

• Numerous syndromic diagnoses and dysmorphic features lead to karyotype analysis.
• When seeking ring chromosomes, in particular ring chromosome 20, it is important to remember that because of mosaicism there might be only 0.5% of mitoses with ring 20 so that 200 mitoses may need to be counted.

FISH and MLPA for subtelomeric deletions and duplications

FISH (fluorescent in situ hybridization) analysis

• method of seeking microdeletions and duplications near the ends of chromosomes and in certain 'hot-spot interstitial regions
• Prader-Willi, Williams and Smith-Magenis syndromes are three good examples
• Submicroscopic deletions and duplications near the end of the chromosomes (subtelomeric) are present in 2-5% of children with dysmorphism and learining disability e.g. 1p36 deletion syndrome

MLPA (multiplex ligation-dependent probe amplification)

• method of detecting minute microdeletions or duplications of genetic material encompassing several or more genes
• This technique employs selected DNA probes that are grouped together in different 'kits' specifically manufactured to analyse selected chromosome regions. MLPA has also been used to detect very small deletions and duplications of genetic material that occur within genes (exon deletion and duplication) that might not be detected by conventional DNA sequencing techniques.
• E.g.  with Dravet syndrome (SCN1A), hereditary spastic paraplegia (.SPAST) etc
• Targeted MLPA to detect duplications of the MECP2 gene in boys.

Array comparative genomic hybridization ( Array CGH)

• detect microdeletions and microduplications of genetic material in up to 15% of children with learning disability, dysmorphism, growth retardation and microcephaly who were previously undiagnosed
• e.g. chromosome 3q29 deletion in childrend with autism spectrum disorder and learning disability

Single gene mutation analysis

• specific analysis of the suspected gene (TREX1) in neonatal Aicardi-Goutieres syndrome