Diagnosis in Dysmorphology: Clues From the Skin

S.F. Smithson; R.M. Winter


The British Journal of Dermatology. 2004;151(5) 

In This Article

Skin Biopsy

Skin biopsy is a simple yet informative investigation in syndrome diagnosis. Apart from routine histology, fibroblasts can be cultured and used for biochemical testing, chromosome analysis, and as a source of DNA for mutation analysis and for specialized tests for specific syndromes, provided that part of the biopsy is put into tissue culture medium. The diagnostic test for Cockayne syndrome (a progressive neurological disorder with sun sensitivity in infancy, a later-onset characteristic facial appearance and loss of subcutaneous tissue around the eyes, microcephaly, sensorineural hearing loss and central and peripheral demyelination[42]) involves detecting a slow rate of recovery of messenger RNA by ultraviolet-irradiated fibroblasts.[43]

Histology of the skin or ultrastructural study by electron microscopy may also reveal interesting findings. Some patients with Apert syndrome (craniosynostosis and severe syndactyly of the hands and feet) have fair hair and pale irides.[44] Electron microscopy of skin biopsies of Apert patients with these skin changes shows melanocytes with very sparse melanosomes, which are small and depleted of melanin (Professor Robin Eady, personal communication). Apert syndrome is caused by mutations in FGFR2,[45] a membrane-bound receptor involved in cell signalling, but a specific role in melanin processing or transport has not been established. Interestingly, somatic mutations in FGFR2 have been identified in DNA derived from skin cells in patients with acne who do not have Apert syndrome.[46]

Skin biopsy may also be the only diagnostic test to confirm mosaic single gene disorders (for example, McCune Albright syndrome, Fig. 4) or mosaic chromosome disorders such as Pallister-Killian syndrome (due to tetrasomy of chromosome 12p[47]), hypomelanosis of Ito[27] and triploidy,[48] as blood chromosomes may be reported as normal in these conditions.

The asymmetrical skin pigmentation seen in McCune Albright syndrome is associated with mutation of the GNAS1 gene in some but not all cells (somatic mosaicism).


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