Diastrophic dysplasia is an
autosomal
An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosome, allosomal (sex chromosome) pairs, which may have different structures. The DNA in au ...
recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
dysplasia
Dysplasia is any of various types of abnormal growth or development of cells (microscopic scale) or organs (macroscopic scale), and the abnormal histology or anatomical structure(s) resulting from such growth. Dysplasias on a mainly microscopic ...
which affects
cartilage
Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck an ...
and
bone
A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...
development. ("Diastrophism" is a general word referring to a twisting.)
Diastrophic dysplasia is due to mutations in the ''
SLC26A2
The sulfate transporter is a solute carrier family protein that in humans is encoded by the ''SLC26A2'' gene. SLC26A2 is also called the diastrophic dysplasia sulfate transporter (DTDST), and was first described by Hästbacka et al. in 1994. A de ...
'' gene.
Affected individuals have short stature with very short arms and legs and joint problems that restrict mobility.
Signs and symptoms
This condition is also characterized by an unusual
clubfoot
Clubfoot is a birth defect where one or both feet are rotated inward and downward. Congenital clubfoot is the most common congenital malformation of the foot with an incidence of 1 per 1000 births. In approximately 50% of cases, clubfoot aff ...
with twisting of the metatarsals, inward- and upward-turning
foot
The foot ( : feet) is an anatomical structure found in many vertebrates. It is the terminal portion of a limb which bears weight and allows locomotion. In many animals with feet, the foot is a separate organ at the terminal part of the leg made ...
, tarsus varus and inversion adducted appearances. Furthermore, they classically present with
scoliosis
Scoliosis is a condition in which a person's spine has a sideways curve. The curve is usually "S"- or "C"-shaped over three dimensions. In some, the degree of curve is stable, while in others, it increases over time. Mild scoliosis does not t ...
(progressive curvature of the
spine) and unusually positioned thumbs (
hitchhiker's thumb
Hitchhiker's thumb, also known as ''distal hyperextensibility of the thumb'' is the condition of having a thumb that has a distal phalange that bends backwards in an angle of 90°, it is thought to be inherited in an autosomal recessive manner, h ...
s). About half of infants with diastrophic dysplasia are born with an opening in the roof of the mouth called a
cleft palate
A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The te ...
. Swelling of the external
ear
An ear is the organ that enables hearing and, in mammals, body balance using the vestibular system. In mammals, the ear is usually described as having three parts—the outer ear, the middle ear and the inner ear. The outer ear consists of ...
s is also common in newborns and can lead to thickened, deformed ears.
The signs and symptoms of diastrophic dysplasia are similar to those of another skeletal disorder called
atelosteogenesis, type 2
Atelosteogenesis, type II is a severe disorder of cartilage and bone development. It is rare, and infants with the disorder are usually stillborn; those who survive birth die soon after.
Symptoms and signs
Infants born with this condition have ve ...
; however diastrophic dysplasia tends to be less severe.
Genetic
It is one of a spectrum of skeletal disorders caused by
mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
s in the ''
SLC26A2
The sulfate transporter is a solute carrier family protein that in humans is encoded by the ''SLC26A2'' gene. SLC26A2 is also called the diastrophic dysplasia sulfate transporter (DTDST), and was first described by Hästbacka et al. in 1994. A de ...
''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
. The protein encoded by this gene is essential for the normal development of cartilage and for its conversion to bone. Cartilage is a tough, flexible tissue that makes up much of the
skeleton
A skeleton is the structural frame that supports the body of an animal. There are several types of skeletons, including the exoskeleton, which is the stable outer shell of an organism, the endoskeleton, which forms the support structure inside ...
during early development. Most cartilage is later converted to bone, but in adulthood this tissue continues to cover and protect the ends of bones and is present in the nose and external ears. Mutations in the ''SLC26A2'' gene alter the structure of developing cartilage, preventing bones from forming properly and resulting in the skeletal problems characteristic of diastrophic dysplasia.
This condition is an
autosomal recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
disorder, meaning that the defective gene is located on an
autosome
An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosome, allosomal (sex chromosome) pairs, which may have different structures. The DNA in au ...
, and both parents must carry one copy of the defective gene in order to have a child born with the disorder. The parents of a child with an autosomal recessive disorder are usually not affected by the disorder.
Prevalence
Diastrophic dysplasia affects about one in 500,000 births, however; in
Finland
Finland ( fi, Suomi ; sv, Finland ), officially the Republic of Finland (; ), is a Nordic country in Northern Europe. It shares land borders with Sweden to the northwest, Norway to the north, and Russia to the east, with the Gulf of B ...
, this disorder is more common, with about in 1 in 33,000 births being affected by the disorder.
See also
*
Achondrogenesis type 1B
Achondrogenesis, type 1B is a severe autosomal recessive skeletal disorder, invariably fatal in the perinatal period.
Achondrogenesis ...
References
''This article incorporates some public domain text fro
The U.S. National Library of Medicine'
External links
GeneReviews/NCBI/NIH/UW entry on Diastrophic Dysplasia
{{Solute carrier disorders
Autosomal recessive disorders