Diastrophic Dysplasia

The term "diastrophic" is Greek and means "crooked". Although diastrophic dysplasia occurs in most countries, the highest prevalence is found in Finland (1 in 33,000) where the carrier rate in the population is 1 – 2% (3). The incidence in non-Finnish populations is considerably lower, being 1 in 500,000 live births (6).

How Diastrophic Dysplasia Is Inherited

Diastrophic dysplasia is inherited as an autosomal recessive trait, with very wide variability of phenotypic expression. Approximately 5% of cases constitute new mutations (6).

Causes of Diastrophic Dysplasia

Diastrophic dysplasia is caused by a mutation in the gene coding for a sulfate transporter protein that is essential for normal cartilage function. This protein is called DTDST and was first identified by Hastbacka and colleagues in 1994 (1). The gene is located on chromosome 5 (5q31-q34). Mutations in the same gene are responsible for lethal chondrodysplasias.

Proteoglycans are complex molecules that absorb water and facilitate load bearing in articular cartilage. Reduction in sulfate transporter concentrations in chondrocytes causes undersulfation of the proteoglycan matrix and predisposes individuals to early degenerative joint disease. Diastrophic dysplasia affects chondrocyte function in the growth plate, epiphyseal region and other areas such as the trachea.

Physical Characteristics

The physical characteristics of diastrophic dysplasia include a short limbed form of disproportionate short stature. Both joint dislocations and joint contractures can be present. Intelligence is typically average.

Face and Skull
  • narrow nasal bridge and broad midportion of the nose
  • long and broad philtrum
  • high, broad forehead
  • square jaw
  • cleft palate in approximately 50% of children
  • capillary hemangiomas called an "Angel's kiss" can be present in the midforehead region. They will disappear or fade with time.
  • in the majority of patients in first 2 weeks of life, cystic swellings of the ear appear but resolve spontaneously, resulting in the characteristic “cauliflower ear” deformity.
Trunk, Chest and Spine:
Arms and Legs:
  • shortening of limbs
  • "Hitchhiker’s thumb." Due to poor development of the bone supporting the thumb, the main thumb joint deviates outwards
  • limited movement of the fingers due to symphalangism
  • dislocations of the elbow and shoulder
  • dislocated kneecap
  • clubfoot
  • abnormal gait
  • weight bearing on balls of feet and toes with compensatory knee and hip flexion
What Are the X-Ray Characteristics?

The radiographic features of Diastrophic Dysplasia include short and broad long bones of the limbs. The metaphyses are flared and crescent-shaped, and flattened epiphyses are typical. The epiphyses of the proximal tibias are triangular and larger than those of the distal femoral epiphyses. The metacarpals, metatarsals, and phalanges are deformed and shortened. Cervical kyphosis and thoracolumbar kyphoscoliosis are characteristic at different ages. There is a moderate narrowing of the interpediculate distances within the lower lumbar segments of spine. The hips are either partially or completely dislocated.


Making the Diagnosis

The condition is typically recognized at birth based on physical and radiographic evaluation. Milder variants or atypical cases may not be diagnosed until a later age. If suspicions arise during a prenatal ultrasound, molecular testing can be done from an amniocentesis sample.

In parents who already have children with diastrophic dysplasia, an ultrasound scan or molecular genetic testing (using DNA from amniocentesis or chorionic villus sampling) in the first trimester of pregnancy offers the possibility of prenatal diagnosis of this condition.

Musculoskeletal Problems
Cervical Spine

Cervical kyphosis is present in 30 – 50% of individuals. It is due to hypoplasia of the vertebral bodies and progressive degenerative changes in the intervertebral joints. Kyphosis can be sufficiently severe and will cause a predisposition to spinal cord compression and quadriplegia (weakness of all 4 extremities and incontinence). Short, sharply angulated curves are associated with severe kyphosis and increase the incidence of neurological abnormalities. Surgery may be necessary to alleviate the spinal cord compression in the neck. A halo and vest device is usually employed after surgery to support the neck until stable fusion is achieved. Occasionally, the kyphosis will resolve spontaneously.

Thoracolumbar Spine

Scoliosis, although not apparent at birth, will become severe as weight bearing increases. The curves usually develop around 5 years of age but can develop even before walking age. The spine curvature causes trunk deformity and barrel chest. Three distinct patterns of scoliosis occur: early progressive, idiopathic-type and mild non-progressive. Kyphoscoliosis occurs frequently (up to 90% of patients) in the lumbar region of the spine. Lumbar lordosis is increased due to exaggerated thoracic kyphosis and concomitant hip flexion contractures (hip joint is fixed with the thigh bent forwards).

Severe Clubfoot

Severe clubfoot is almost always present and typically requires surgical release. Surgery is usually undertaken around 1-year of age, to enable the child to start walking. In spite of early intervention, recurrence of the foot deformity is common and an osteotomy may become necessary. Special shoes are oftentimes required.

Progressive Subluxation

Progressive subluxation of the hips occurs because the soft articular cartilage is unable to perform its normal function of load bearing. Superimposed joint contractures around the hips and knees lead to restricted movement and deformity. If the deformity interferes with walking, an osteotomy is performed around the hips or knees. Due to the intrinsic cartilage abnormality, degenerative joint disease (arthritis) is common. Flexion deformities are pronounced. Knees are dislocated. Hip or knee replacement surgery is usually necessary in early to mid-adult life and typically has successful results.

Problems Elsewhere in the Body
Respiratory Obstruction

Respiratory obstruction, including laryngeal stenosis, may occur in newborns. The mortality rate due to respiratory distress can approach 25% in early infancy.

Hypoplastic Cartilage

Hypoplastic cartilage in the trachea and larynx causes voice abnormalities and breathing difficulty.

Small Auditory Canals

Small auditory canals are characteristic, but this does not usually impair hearing. However, deformity of the middle ear ossicles can result in
hearing loss.

In infancy, it is important to be regularly monitored by a pediatric orthopedic surgeon so that future problems of the feet and spine can be managed and possibly evaded. Surgery is usually performed before walking age to correct foot deformities.

Later in life, patients must look out for worsening foot deformities, progressive curvature of the spine, and hip pain in early adult life (due to arthritis). Common surgical procedures intended to correct these problems include an osteotomy of the foot or lower leg (to achieve a plantigrade foot) or hip replacement surgery (for progressive degenerative arthritis).

What to Look for

Occasionally, spinal cord compression in the neck can lead to quadriparesis, resulting in a loss of limb function. Symptoms to watch for include a loss of walking or reduced endurance, altered sensations in the arms and legs, or incontinence. Oftentimes patients undergo spinal fusion surgery in the neck or lower back, along with decompression of the spinal cord.

Generally all skeletal dysplasias warrant multidisciplinary attention. Regular assessment by an orthopedist, geneticist, pediatrician, dentist, neurologist, and physical therapist will provide the most comprehensive treatment.

  1. Hastbacka, J.; Sistonen, P.; Kaitila, I.; Weiffenbach, B.; Kidd, K. K.; de la Chapelle, A. : A linkage map spanning the locus for diastrophic dysplasia (DTD). Genomics 11: 968-973, 1991.
  2. Jones, Kenneth L. Recognizable Patterns of Human Malformation. Philadelphia, PA: Elsevier Saunders. 2006.
  3. Poussa, Mikko. Merikanto, Juhani. Ryoppy, Soini. Marttinen, Eino. Kaitila, Ilkka. The Spine in Diastrophic Dysplasia. Spine; 16(8):881-887. 1991.
  4. Scott, Charles I. Dwarfism. Clinical Symposium, 1988; 40(1):9-10.
  5. Spranger, Jurgen W. Brill, Paula W. Poznanski, Andrew. Bone Dysplasias: An Atlas of Genetic Disorder of Skeletal Development. Oxford: Oxford University Press. 2002.
  6. Diastrophic Dysplasia Booklet http://pixelscapes.com/ddhelp/DD-booklet/

Genetic Testing

Genetic tests are done by analyzing small samples of blood or body tissues. They determine whether you, your partner, or your baby carry genes for certain inherited disorders.

Genetic testing has developed enough so that doctors can often pinpoint missing or defective genes. The type of genetic test needed to make a specific diagnosis depends on the particular illness that a doctor suspects.

Many different types of body fluids and tissues can be used in genetic testing. For deoxyribonucleic acid (DNA) screening, only a very tiny bit of blood, skin, bone, or other tissue is needed.

Genetic Testing During Pregnancy

For genetic testing before birth, pregnant women may decide to undergo amniocentesis or chorionic villus sampling. There is also a blood test available to women to screen for some disorders. If this screening test finds a possible problem, amniocentesis or chorionic villus sampling may be recommended.

Amniocentesis is a test usually performed between weeks 15 and 20 of a woman's pregnancy. The doctor inserts a hollow needle into the woman's abdomen to remove a small amount of amniotic fluid from around the developing fetus. This fluid can be tested to check for genetic problems and to determine the sex of the child. When there's risk of premature birth, amniocentesis may be done to see how far the baby's lungs have matured. Amniocentesis carries a slight risk of inducing a miscarriage.

Chorionic villus sampling (CVS) is usually performed between the 10th and 12th weeks of pregnancy. The doctor removes a small piece of the placenta to check for genetic problems in the fetus. Because chorionic villus sampling is an invasive test, there's a small risk that it can induce a miscarriage.

Why Doctors Recommend Genetic Testing

A doctor may recommend genetic counseling or testing for any of the following reasons:

  • A couple plans to start a family and one of them or a close relative has an inherited illness. Some people are carriers of genes for genetic illnesses, even though they don't show, or manifest, the illness themselves. This happens because some genetic illnesses are recessive — meaning that they're only expressed if a person inherits two copies of the problem gene, one from each parent. Offspring who inherit one problem gene from one parent but a normal gene from the other parent won't have symptoms of a recessive illness but will have a 50% chance of passing the problem gene on to their children.
  • A parent already has one child with a severe birth defect. Not all children who have birth defects have genetic problems. Sometimes, birth defects are caused by exposure to a toxin (poison), infection, or physical trauma before birth. Often, the cause of a birth defect isn't known. Even if a child does have a genetic problem, there's always a chance that it wasn't inherited and that it happened because of some spontaneous error in the child's cells, not the parents' cells.
  • A woman has had two or more miscarriages. Severe chromosome problems in the fetus can sometimes lead to a spontaneous miscarriage. Several miscarriages may point to a genetic problem.
  • A woman has delivered a stillborn child with physical signs of a genetic illness. Many serious genetic illnesses cause specific physical abnormalities that give an affected child a very distinctive appearance.
  • The pregnant woman is over age 34. Chances of having a child with a chromosomal problem (such as trisomy) increase when a pregnant woman is older. Older fathers are at risk to have children with new dominant genetic mutations (those caused by a single genetic defect that hasn't run in the family before).
  • A standard prenatal screening test had an abnormal result. If a screening test indicates a possible genetic problem, genetic testing may be recommended.
  • A child has medical problems that might be genetic. When a child has medical problems involving more than one body system, genetic testing may be recommended to identify the cause and make a diagnosis.
  • A child has medical problems that are recognized as a specific genetic syndrome. Genetic testing is performed to confirm the diagnosis. In some cases, it also might aid in identifying the specific type or severity of a genetic illness, which can help identify the most appropriate treatment.

A Word of Caution

Although advances in genetic testing have improved doctors' ability to diagnose and treat certain illnesses, there are still some limits. Genetic tests can identify a particular problem gene, but can't always predict how severely that gene will affect the person who carries it. In cystic fibrosis, for example, finding a problem gene on chromosome number 7 can't necessarily predict whether a child will have serious lung problems or milder respiratory symptoms.

Also, simply having problem genes is only half the story because many illnesses develop from a mix of high-risk genes and environmental factors. Knowing that you carry high-risk genes may actually be an advantage if it gives you the chance to modify your lifestyle to avoid becoming sick.

As research continues, genes are being identified that put people at risk for illnesses like cancer, heart disease, psychiatric disorders, and many other medical problems. The hope is that someday it will be possible to develop specific types of gene therapy to totally prevent some diseases and illnesses.

Gene therapy is already being studied as a possible way to treat conditions like cystic fibrosis, cancer, and ADA deficiency (an immune deficiency), sickle cell disease, hemophilia, and thalassemia. However, severe complications have occurred in some patients receiving gene therapy, so current research with gene therapy is very carefully controlled.

Although genetic treatments for some conditions may be a long way off, there is still great hope that many more genetic cures will be found. The Human Genome Project, which was completed in 2003, identified and mapped out all of the genes (about 25,000) carried in our human chromosomes. The map is just the start, but it's a very hopeful beginning.

Reviewed by: Larissa Hirsch, MD
Date reviewed: September 26, 2016