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).
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.
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.
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
- 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.
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.
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.
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 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 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.
Respiratory obstruction, including laryngeal stenosis, may occur in newborns. The mortality rate due to respiratory distress can approach 25% in early infancy.
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
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).
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.
- 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.
- Jones, Kenneth L. Recognizable Patterns of Human Malformation. Philadelphia, PA: Elsevier Saunders. 2006.
- Poussa, Mikko. Merikanto, Juhani. Ryoppy, Soini. Marttinen, Eino. Kaitila, Ilkka. The Spine in Diastrophic Dysplasia. Spine; 16(8):881-887. 1991.
- Scott, Charles I. Dwarfism. Clinical Symposium, 1988; 40(1):9-10.
- Spranger, Jurgen W. Brill, Paula W. Poznanski, Andrew. Bone Dysplasias: An Atlas of Genetic Disorder of Skeletal Development. Oxford: Oxford University Press. 2002.
- Diastrophic Dysplasia Booklet http://pixelscapes.com/ddhelp/DD-booklet/
From Nemours' KidsHealth
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Prenatal Genetic Counseling
If you and your partner are newly pregnant, you may be amazed at the number and variety of prenatal tests available to you. Blood tests, urine tests, monthly medical exams, screening tests, and family history tracking — each helps to assess the health of you and your baby, and to predict any potential health risks.
You may also have the option of genetic testing. These tests identify the likelihood of passing certain genetic diseases or disorders (those caused by a defect in the genes — the tiny, DNA-containing units of heredity that determine the characteristics and functioning of the entire body) to your children.
Some of the more familiar genetic disorders are:
- Down syndrome
- cystic fibrosis
- sickle cell disease
- Tay-Sachs disease (a fatal disease affecting the central nervous system)
If your history suggests that genetic testing would be helpful, you may be referred to a genetic counselor. Or, you might decide to seek out genetic counseling yourself.
But what do genetic counselors do, and how can they help your family?
What Is Genetic Counseling?
Genetic counseling is the process of:
- evaluating family history and medical records
- ordering genetic tests
- evaluating the results of this investigation
- helping parents understand and reach decisions about what to do next
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.
Genes are made up of DNA molecules, which are the building blocks of heredity. They're grouped together in specific patterns within a person's chromosomes, forming the unique "blueprint" for every physical and biological characteristic of that person.
Humans have 46 chromosomes, arranged in pairs in every living cell of our bodies. When the egg and sperm join at conception, half of each chromosomal pair is inherited from each parent. This newly formed combination of chromosomes then copies itself again and again during fetal growth and development, passing identical genetic information to each new cell in the growing fetus.
Current science suggests that every human has about 25,000 genes per cell. An error in just one gene (and in some instances, even the alteration of a single piece of DNA) can sometimes be the cause for a serious medical condition.
Some diseases, such as Huntington's disease (a degenerative nerve disease) and Marfan syndrome (a connective tissue disorder), can be inherited from just one parent. But most disorders, including cystic fibrosis, sickle cell anemia, and Tay-Sachs disease, cannot occur unless both the mother and father pass along the gene.
Other genetic conditions, such as Down syndrome, are usually not inherited. In general, they result from an error (mutation) in the cell division process during conception or fetal development. Still others, such as achondroplasia (the most common form of dwarfism), may either be inherited or the result of a genetic mutation.
Genetic tests don't yield easy-to-understand results. They can reveal the presence, absence, or malformation of genes or chromosomes. Deciphering what these complex tests mean is where a genetic counselor comes in.
About Genetic Counselors
Genetic counselors are professionals who have completed a master's program in medical genetics and counseling skills. They then pass a certification exam administered by the American Board of Genetic Counseling.
Genetic counselors can help identify and interpret the risks of an inherited disorder, explain inheritance patterns, suggest testing, and lay out possible scenarios. (They refer you to a doctor or a laboratory for the actual tests.) They will explain the meaning of the medical science involved, provide support, and address any emotional issues raised by the results of the genetic testing.
Who Should See One?
Most couples planning a pregnancy or who are expecting don't need genetic counseling. About 3% of babies are born with birth defects each year, according to the Centers for Disease Control and Prevention (CDC) — and of the malformations that do occur, the most common are also among the most treatable. Cleft palate and clubfoot, two of the more common birth defects, can be surgically repaired, as can many heart malformations.
The best time to seek genetic counseling is before becoming pregnant, when a counselor can help assess your risk factors. But even after you become pregnant, a meeting with a genetic counselor can still be helpful. A genetic counselor can help determine what testing is appropriate for your pregnancy.
Experts recommend that all pregnant women, regardless of age or circumstance, be offered genetic counseling and testing to screen for Down syndrome.
It's especially important to consider genetic counseling if any of the following risk factors apply to you:
- a standard prenatal screening test (such as the alpha fetoprotein test) yields an abnormal result
- an amniocentesis yields an unexpected result (such as a chromosomal defect in the unborn baby)
- either parent or a close relative has an inherited disease or birth defect
- either parent already has children with birth defects, intellectual disabilities, or genetic disorders
- the mother-to-be has had two or more miscarriages or babies that died in infancy
- the mother-to-be will be 35 or older when the baby is born. Chances of having a child with Down syndrome increase with the mother's age: a woman has about a 1 in 350 chance of conceiving a child with Down syndrome at age 35, a 1 in 110 chance at age 40, and a 1 in 30 chance at age 45.
- you are concerned about genetic defects that occur frequently in certain ethnic or racial groups. For example, couples of African descent are most at risk for having a child with sickle cell anemia; couples of central or eastern European Jewish (Ashekenazi), Cajun, or Irish descent may be carriers of Tay-Sachs disease; and couples of Italian, Greek, Middle Eastern, southern Asian, or African descent may carry the gene for thalassemia, a red blood cell disorder.
- either parent is concerned about the effects of exposures they have had to radiation, medications, illegal drugs, infections, or chemicals
Meeting With a Genetic Counselor
Before you meet with a genetic counselor in person, you may be asked to gather information about your family history. The counselor will want to know of any relatives with genetic disorders, multiple miscarriages, and early or unexplained deaths. The counselor will also want to look over your medical records, including any ultrasounds, prenatal test results, past pregnancies, and medications you may have taken before or during pregnancy.
When you meet with the counselor, you'll go over any gaps or potential problem areas in your family or medical history. The counselor can help you understand the inheritance patterns of any potential disorders and help assess your chances of having a child with those disorders.
The counselor will distinguish between risks that every pregnancy faces and risks that you personally face. Even if you discover you have a particular problem gene, science can't always predict the severity of the related disease. For instance, a child with cystic fibrosis can have debilitating lung problems or, less commonly, milder respiratory symptoms.
If more tests are necessary, the counselor will help you set up those appointments and track the paperwork. When the results come in, the counselor will call you with the news and may ask you to come in for another discussion.
Genetic counselors can help you understand your options and adjust to any uncertainties you face, but you and your family will have to decide what to do next.
If you've learned before conception that you and/or your partner are at high risk for having a child with a severe or fatal defect, your options might include:
- pre-implantation diagnosis — when eggs that have been fertilized in vitro (in a laboratory, outside of the womb) are tested for defects at the 8-cell (blastocyst) stage, and only nonaffected blastocysts are implanted in the uterus to establish a pregnancy
- using donor sperm or donor eggs
- taking the risk and having a child
- establishing pregnancy and have specific prenatal testing
If you've received a diagnosis of a severe or fatal defect after conception, your options might include:
- preparing yourself for the challenges you'll face when you have your baby
- fetal surgery to repair the defect before birth (surgery can only be used to treat some defects, such as spina bifida or congenital diaphragmatic hernia, a hole in the diaphragm that can cause severely underdeveloped lungs. Most defects cannot be surgically repaired.)
- ending the pregnancy
For some families, knowing that they'll have an infant with a severe or fatal genetic condition seems too much to bear. Other families are able to adapt to the news — and to the birth — remarkably well.
Genetic counselors can share the experiences they've had with other families in your situation. But they will not suggest a particular course of action. A genetic counselor understands that what is right for one family may not be right for another.
Genetic counselors can, however, refer you to specialists for further help. For instance, many babies with Down syndrome are born with heart defects. Your counselor might encourage you to meet with a cardiologist to discuss heart surgery, and a neonatologist to discuss the care of a post-operative newborn. Genetic counselors can also refer you to social workers, support groups, or mental health professionals to help you adjust to and prepare for your complex new reality.
Finding a Genetic Counselor
Working with a genetic counselor can be reassuring and informative, especially if you or your partner have known risk factors. Talk to your doctor if you feel you would benefit from genetic counseling. Many doctors have a list of local genetic counselors they work with. You also can contact the National Society of Genetic Counselors for more information.
Reviewed by: Larissa Hirsch, MD
Date reviewed: August 11, 2016