Congenital adrenal hyperplasia—a continuum of disorders

IA Hughes - The Lancet, 1998 - thelancet.com
The Lancet, 1998thelancet.com
Infertility spectrum in CAH and is another reason for disease variability. A recent report11 of
a kindred with classic CAH clearly illustrates how clinical presentation can vary despite
identical CYP21 mutations. The male proband showed no salt loss soon after birth but
developed signs of virilisation within a few months. A sister developed signs of virilisation by
2 years of age. Another sister was said to be normal at birth, yet when re-examined at 5 days
of age after a positive biochemical screening test, she had an enlarged clitoris (1· 5 cm) and …
Infertility spectrum in CAH and is another reason for disease variability. A recent report11 of a kindred with classic CAH clearly illustrates how clinical presentation can vary despite identical CYP21 mutations. The male proband showed no salt loss soon after birth but developed signs of virilisation within a few months. A sister developed signs of virilisation by 2 years of age. Another sister was said to be normal at birth, yet when re-examined at 5 days of age after a positive biochemical screening test, she had an enlarged clitoris (1· 5 cm) and partial labial fusion. Two paternal aunts also had CAH; one had had severe salt wasting at presentation in infancy. All five affected individuals in this kindred were compound heterozygotes for the common intron-2 splice mutation and for a non-conservative mis-sense mutation (isoleucine 172 asparagine), which is generally associated with the classic non-salt-wasting form of CAH. Sequencing of the entire CYP21 gene and part of the promoter region in the two affected adults revealed no additional mutations in this family to account for the phenotypic variability.
CAH is thus a continuum of disorders that manifest as a spectrum of disease classified according to age of presentation and symptoms and signs. Added to the complexity are the biochemical indices of enzyme deficiency, especially well illustrated by results obtained in programmes for screening of the newborn, and the variety of gene mutations that are now well characterised. Nevertheless, in an analysis of a large number of patients from five different populations, the concordance between genotype and phenotype in CAH was remarkably consistent in most cases. 12 This
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