Dysplasia Health Article

Generalized dysplasia

A generalized dysplasia often presents as multiple malformations in a variety of structures. Any structural consequences are due to the particular tissue organization defect and the spectrum of organs that utilize the dysplastic tissue. Generalized dysplasias are often genetic. They may be inherited or occur due to a new genetic change in an individual. The structural problems associated with generalized dysplasias usually begin during embryonic development.

This type of dysplasia is classified according to the specific tissue affected. Generalized dysplasias account for some important groups of inherited disorders including the skeletal dysplasias and ectodermal dysplasias.

SKELETAL DYSPLASIAS Skeletal dysplasias affect the growth, organization, and development of the bony skeleton. These conditions are always genetic. The effects of skeletal dysplasias vary. A mild skeletal dysplasia may cause someone to be of shortened height without any other complication. Other skeletal dysplasias may severely reduce height, causing dwarfism with disproportion and other bone deformity. The most severe

skeletal dysplasias are incompatible with life, causing babies to die before or soon after birth.

The skeletal dysplasias include achondroplasia, hypochondroplasia, thanatophoric dysplasia, achondrogenesis, diastrophic dysplasia, atelosteogenesis, spondyloepiphyseal dysplasia, Kniest dysplasia, Stickler syndrome, pseudoachondoplasia, metaphyseal dysplasia, and several others.

Achondroplasia is a common, highly recognizable skeletal dysplasia. This disorder occurs in approximately one in 20,000 live births. Achondroplasia affects bone growth resulting in short stature, a large head, characteristicfacial features, and disproportionately short arms and legs. This disorder is caused by a mutation in a single gene called fibroblast growth gactor receptor three (FGFR3). Achondroplasia may be inherited like most generalized dysplasias, but more commonly it occurs due to a new mutation in a family. Over 80% of cases of achondroplasia are sporadic, or due to new mutations. The appearance of new mutations for achondroplasia is more frequently observed in children born to older fathers.

Hypochondroplasia is a common, milder skeletal dysplasia caused by different mutations in the gene responsible for achondroplasia, the FGFR3 gene. People with hypochondroplasia display varying degrees of short stature and disproportion of limbs. People with mild symptoms may never be diagnosed. The body of a person with hypochondroplasia appears short and broad with a long torso and short limbs. Life span is normal. Like achondroplasia, hypochondroplasia is inherited in an autosomal dominant manner.

ECTODERMAL DYSPLASIAS Ectodermal dysplasias affect the growth and development of tissues derived from the early outer layer of embryonic tissue known as the ectoderm. Tissues derived from the ectoderm include hair, fingernails, skin, sweat glands, and teeth. People with ectodermal dysplasias display abnormalities in at least two derivatives of the ectoderm. Ectodermal dysplasia (ED) can take many different forms because so many tissues are derived from the ectoderm. Over 150 types of ectodermal dysplasias have been identified.

The effects of ectodermal dysplasias range from mild to severe. They are divided into two major groups based on the presence or absence or normal sweating. Sweat production is normal in hidrotic (sweating) types and reduced in hypohidrotic (decreased sweating) types. Types with reduced or absent sweating are generally more severe.

Christ-Siemens-Touraine syndrome (CST), a hypohidrotic (decreased sweating) ectodermal dysplasia, is a common, well-understood type of ectodermal dysplasia. People with this type of ectodermal dysplasia are not able to sweat or form tears normally. They are very sensitive to light and are not able to control their body temperature well due to their reduced sweating. Intelligence is normal. People with CST often have small or missing teeth, eyebrows, and eyelashes. Head hair is usually sparse, but fingernails are normal. CST is usually X-linked recessive, affecting only males with full symptoms of the disease. In some cases, female carriers show mild symptoms of the disease. Rarer autosomal dominant and autosomal recessive forms can affect males and females.

Clouston ectodermal dysplasia, a hidriotic (sweating) ectodermal dysplasia, also known as ectodermal Dysplasia 2 (ED2) is found more commonly in people of French Canadian descent. People with this form of ED have partial to total baldness with normal teeth, severely abnormal fingernails, and darkly pigmented areas of skin, especially over joints. They have underdeveloped eyebrows and eyelashes and may be born with teeth. They may also have thickened skin on the soles of their feet and the palms of their hands. Features including mental retardation and strabismus, or crossed eyes, may occur with this disorder, however intelligence is usually normal. This form of ED is inherited in an autosomal dominant manner. Any affected person has a 50% chance to pass the disorder to each of their children.