Congenital malformations - Edocr

26 PART I GENERAL CONSIDERATIONS
Figure 3-5. A typical pedigree of an X-linked recessive condition.
pedigree (Fig. 3-5) for typical X-linked recessive
disorders, such as Duchenne or Becker
muscular dystrophy (DMD/BMD) or ornithine
transcarbamylase (OTC) deficiency, can be readily
recognized based on the presence of no male
to male transmission of the disorder and typically
only males are affected in the family. With each
pregnancy, female carriers have a 25% risk of
having an affected son, 25% risk of having an unaffected
son, 25% risk of having a daughter who
is a carrier, and a 25% risk of having a daughter
who is not a carrier. For affected males, all their
daughters will be carriers and a gene copy is
generally not transmitted to their sons.
In some conditions, female carriers of X-linked
recessive disorders can exhibit features of the
condition. This is generally felt to be due to
skewed X inactivation, with the X chromosome
that has the normal gene copy inactivated in
more tissues than the X chromosome with the
gene mutation. In conditions such as Fabry disease,
there is a high number of manifesting carrier
females who have severe enough symptoms
to require enzyme replacement therapy. In fragile
X syndrome, women who are carriers can exhibit
learning disabilities, social immaturity, and premature
ovarian failure.
Disorders that are due to genes located on
the Y sex chromosome are rare. At the time this
chapter was written, only two disorders with
known genes on the Y chromosome and four
disorders suspected of Y-linked inheritance
were reported on the OMIM. A Y-linked disorder
will be readily recognized since only males
will be affected and the condition can only be
transmitted from father to son (Fig. 3-6).
For conditions that are due to mutations in
genes in the pseudoautosomal regions of X and
Y, the pattern of inheritance will be similar to
that observed on autosomal disorders.
Mitochondrial Disorders
The mitochondria are unique organelles in the
human cell because it has its own genome and a