Pycnodysostosis: Get Facts About Symptoms & Treatment

Pycnodysostosis facts

  • Pycnodysostosis is an inherited disorder of the bone.
  • Pycnodysostosis causes short stature.
  • Pycnodysostosis causes abnormally dense brittle bones.
  • Pycnodysostosis causes the "soft spot" of a
    baby’s skull to
    stay widely open.
  • Pycnodysostosis is due to a defect in an enzyme: cathepsin
  • Growth hormone treatment may increase growth in

What is pycnodysostosis?

Pycnodysostosis is perhaps best known as the diagnosis given retrospectively to the late 19th century French artist Henri de Toulouse-Lautrec (portrayed by Jose Ferrer in the 1952 film "Moulin Rouge").

Pycnodysostosis is a genetic (inherited) disease of the bone. Its pattern of inheritance follows the classic rules of genetics (see below).

Pycnodysostosis consistently causes short stature. The height of adult males with the disease is less than 150 cm (59 inches, or 4 feet 11 inches). Adult females with pycnodysostosis are even shorter.

Pycnodysostosis causes the bones to be abnormally dense (osteosclerosis); the last bones of the fingers (the distal phalanges) to be unusually short; and delays the normal closure of the connections (sutures) of the skull bones in infancy, so that the "soft spot" (the fontanel) on top of the head remains widely open.

Pycnodysostosis causes brittle bones which easily break (fracture). The bones in the legs and feet tend to fracture. The jaw and collar bone (clavicles) are also particularly prone to fractures.

The precise frequency of pycnodysostosis has never been determined. Pycnodysostosis can be classified in the large group of genetic diseases that are individually uncommon, but collectively important because of the sum of their numbers, their heavy impact upon affected individuals, and the equally heavy burden they place upon their families.

What is basis for the name of this disease?

The name for this disease was coined by the French physicians
and Lamy in 1962. They described the disorder in a report
entitled "La
pycnodysostose." (They were not the only discoverers of
the disease.
Andren and colleagues independently described the condition in
Maroteaux and Lamy put "pyknos," from the Greek
meaning "dense"
together with the compound word "dysostosis" meaning
bone formation. The name "pycnodysostosis" was
designed to
convey the abnormally dense bone that is a hallmark of the

Although the original Maroteaux and Lamy spelling was with a
‘c’, it has
been written variably with a ‘c’ or a ‘k’. Here we use the
spelling with a ‘c’. No matter which way it is spelt, the name
has stuck
and is utilized worldwide today to designate this disease.

What are the characteristics of pycnodysostosis?

Pycnodysostosis causes abnormalities other than short stature,
brittle bones, short fingers, and the wide open soft spot of
the skull
(see above). These other abnormalities involve the head and
face, teeth,
collar bones, skin, and nails. The front and back of the head
prominent. Within the open sutures of the skull, there may be
many small
bones (called wormian bones). The midface is less full than
usual. The
nose is prominent. The jaw can be small. The palate is narrow
and grooved.
The baby teeth are late coming in and may be lost much later
than usual.
The permanent teeth can also be slow to appear. The permanent
teeth are
commonly irregular and teeth may be missing (hypodontia). The
collar bones
are often underdeveloped and malformed. The skin over the back
of the
fingers is very wrinkled. The nails are flat and grooved.

Pycnodysostosis also causes problems that may become evident
with time.
Aside from the broken bones, the last bones of the fingers (the
phalanges) and the collar bone can undergo slow progressive
Vertebral defects may permit the spine to curve laterally
(resulting in
scoliosis). The tooth problems often require orthodontic care
and dental
cavities are common.

How is pycnodysostosis inherited?

Pycnodysostosis is an autosomal recessive condition. It is
autosomal in
that the gene for pycnodysostosis is situated on one of the non-
chromosomes (autosomes). Pycnodysostosis is recessive in that a
edition of the pycnodysostosis gene is not enough to cause the
Two copies of the abnormal gene (one from each parent) must be
present for
the disease to develop. The presence of a normal gene from one
or both
parents prevents the disease.

What are the risks of pycnodysostosis?

Pycnodysostosis is a rare disease so that, if there is no
family history
of the disease, the risk for a child to have pycnodysostosis is
very low.

However, with a inbred (consanguineous) union, the risk of
pycnodysostosis rises a little. This means that if one parent
carries a
rare gene like that for pycnodysostosis, the chance that a mate
of theirs
who is actually related also carries the same rare gene is
compared to an unrelated mate.

In a family with a child with pycnodysostosis, the risks are
higher. The parents of a child with pycnodysostosis have no
signs of the
disease themselves but they each carry a single edition of the
pycnodysostosis gene and, with a given pregnancy, each has a
half chance
of transmitting the pycnodysostosis gene (versus the normal
paired gene).
It is like tossing a coin. The chance for the child to have
pycnodysostosis is one-half (from one parent) times one-half
(from the
other parent). The overall risk of pycnodysostosis in the
offspring of
parents carrying the gene is, therefore, one-quarter (25%).
Just as coins
have no memory of a prior toss, the 25% odds of having a
child apply to every pregnancy conceived together by these
irrespective of the status of any of their other children.

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What is the molecular story with pycnodysostosis?

In 1995, the gene for pycnodysostosis was first charted by
Gelb and
associates. It was found to travel preferentially with gene
markers known
to be in chromosome region 1q21. (This tendency for genes to
together is termed linkage). Once the location of the
pycnodysostosis gene
was identified by linkage analysis, genes in that region that
logical candidates were seriously scrutinized. Among them was
cathepsin K,
which is active in bone. Cathepsin K qualified as a
"candidate gene."

In 1996, patients with pycnodysostosis were shown by Gelb and
consistently to have mutational changes in the gene for
cathepsin K. The
defective cathepsin K gene was thus demonstrated to be the gene
responsible for pycnodysostosis. Pycnodysostosis is now clearly
as being due to cathepsin K deficiency.

What does cathepsin K normally do? Cathepsin K is an enzyme (a
for a reaction of body metabolism) of the type called a
cysteine protease.
This protease is important in cells of normal bone
(osteoclasts) that are
responsible for bone reabsorption (or resorption). It is
thought that
osteoclasts in patients with pycnodysostosis are hampered by a
lack of
cathepsin K and cannot adequately reabsorb that component of
bone called
the organic matrix. (This process is essential for normal bone
maintenance; a process referred to as remodeling). Because of
inadequate resorption, the bones in pycnodysostosis are
abnormally dense
and brittle.

Could there be a connection between pycnodysostosis and

Both pycnodysostosis and osteoporosis cause brittle bones.
pycnodysostosis is a disease with abnormally dense bones,
osteoporosis is exactly the opposite, a disease with washed-out
bones. There would seem to be no conceivable connection between
pycnodysostosis and osteoporosis.

The new findings about cathepsin K and pycnodysostosis have made it clear
that cathepsin K is a major protease in bone resorption. Given this
function, it may well have a role in osteoporosis. Cathepsin K may, in fact, provide a rational basis for
a new
approach to the treatment of osteoporosis. This is an excellent
illustration of how research on a rare disease may bring
benefits to those
affected by a common disease.


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What is the treatment for pycnodysostosis?

Bone fractures are a big problem for patients with
pycnodysostosis. They
can occur with minimal stress. It is important that the disease
diagnosed and the tendency to fractures be recognized so that
fractures can be minimized, if not entirely prevented; and (2)
the parents
and other caregivers are not falsely accused of child abuse! As
with any
condition causing brittle bones, the infant should be handled
with a
reasonable degree of care. The older child should be encouraged
to engage
in safer forms of exercise such as swimming rather than, for
jumping on a trampoline.

In 1996, Soliman and colleagues reported that there is
secretion of growth hormone in pycnodysostosis. Replacement
treatment with
growth hormone was then tested. It was found to increase the
growth of the
length of bones (linear growth). Since short stature is an
consequence of pycnodysostosis, growth hormone treatment may
prove very

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