Variability

Autosomal recessive disorders usually demonstrate full
penetrance and little clinical variability within families.
Haemochromatosis is unusual in that not all homozygotes
develop clinical disease. Women in particular are protected by
menstruation. In childhood onset SMA type I (Werdnig–Hoffman
disease) there is very little difference in the age at death between
affected siblings. However, the age at onset, severity and age at
death is more variable in intermediate SMA type II. Variation in
the severity of an autosomal recessive disorder between families is
generally explained by the specific mutation present in the gene.
In cystic fibrosis, delta F508 is the most common mutation and
most affected homozygotes have pancreatic insufficiency. Patients
with other particular mutations are more likely to be pancreatic
sufficient, may have less severe pulmonary disease if the
regulatory function of the gene is preserved, or even present
with just congenital absence of the vas deferens.