Pseudoachondroplasia

“Pseudo” means “false.” Thereby, this disorder is one that resembles, but is clinically distinct from, achondroplasia.The incidence of pseudoachondroplasia is estimated at 1 in 30,000, however the birth prevalence is not yet known (2).

 
How Pseudoachondroplasia Is Inherited

Pseudoachondroplasia can either be inherited in an autosomal dominant inheritance pattern (1). Parental germinal mosaicism is often found, which explains why many affected children have unaffected parents. Mosaicism causes the condition to behave in an autosomal recessive fashion.

 
Causes of Pseudoachondroplasia

Pseudoachondroplasia results from a mutation in the gene coding for cartilage oligomeric matrix protein (COMP) (1). COMP is a normal constituent of the extra-cellular matrix in cartilage, ligaments, and tendons. Defective COMP results in the accumulation of proteoglycans within cartilage cells.

 
Physical Characteristics

Both the epiphyses and metaphyses are affected in pseudoachondroplasia. Clinically, it is recognized as a form of short-limbed dwarfism, with body proportions similar to those of achondroplasia, yet with normal-sized heads and facial features.

The postnatal onset of short-limbed growth deficiency will not become apparent until between 18 and 24 months of age. Pseudoachondroplasia manifests itself over time. Ultimately, adult stature is between
82 and 130 cm.

Face & Skull
  • Normal head size and facial features
Trunk, Chest, & Spine:
Arms & Legs:
What are the X-ray characteristics?

The radiographic features of pseudoachondroplastic patients include short and broad long bones with flaring of the metaphyses. Epiphyseal ossification is delayed. The epiphyses appear irregular and fragmented. The hips and knees are primarily affected. Due to their dysplastic nature, the carpals ossify late.

In the pelvis, the acetabulum (hip socket) is shallow and accentuates hip dysplasia. The triradiate cartilage is also late to mature and ossify. Arthrograms are helpful in identifying joint surfaces and planning surgery for angular deformities. The capital femoral epiphyses are small and irregular in children; in adults, there is marked dysplasia of the femoral head. The femoral head is flattened and fragmented. This leads to hip joint incongruity and exacerbates the effects of hip subluxation.

X-rays of the spine show platyspondyly and flame-shaped anterior projections. The interpedicular distance does not progressively decrease in the lumbar spine. In the neck, lateral X-rays of the cervical spine may reveal odontoid hypoplasia. The vertebrae will at first seem deformed, but the irregularities generally disappear by adolescence. Flexion-extension radiographs should be obtained to rule out atlantoaxial instability. MRI scans of the cervical spine (static, flexion/extension views and CSF flow studies) are helpful in identifying any compression of the spinal cord.

 
Making the Diagnosis

The average length at birth is 49 cm, which is within the normal range. Pseudoachondroplasia is therefore not readily recognized at birth. But, lack of longitudinal growth manifests itself in the first 2 years of life (below 5th percentile on standard growth charts). By this point the abnormal gait is present and measurements suggest pseudoachondroplasia. Diagnosis is typically made between 1 and 4 years of age and is based on clinical examination and characteristic X-ray appearances. Prenatal testing is now available by direct DNA analysis. The test detects the abnormal COMP gene by mutation scanning. Prenatal diagnosis may be appropriate during pregnancy in women with pseudoachondroplasia. It must be stressed that the majority of cases are spontaneous mutations.

 
Musculoskeletal Problems
Spine

The cervical spine should be monitored for the presence of atlantoaxial instability. Lateral flexion-extension x-rays of the cervical spine is recommended, if a pre-existing abnormality such as hypoplastic odontoid is present. Posterior cervical decompression and fusion should be performed if the instability exceeds 8 mm or neurological symptoms (cervical myelopathy) occur. Scoliosis should be looked for and is managed similar to idiopathic curves. Lateral c-spine x-rays should be routinely obtained in all children with pseudoachondroplasia undergoing surgery for any reason.

Lower Limbs

Angular deformities around the knee are corrected using osteotomies. Careful pre-operative planning is essential to restore normal mechanical axes in sagittal and coronal planes (down the middle of the body). Since the epiphyses are distorted, intraoperative arthrography may be necessary to properly visualize the joint surfaces. The effect of ligamentous laxity on alignment should be ascertained as part of the pre-operative planning. Recurrence of deformity is common and several procedures may be necessary to achieve lower extremity skeletal alignment at maturity. Up to 50% of adults will require joint replacement surgery for early onset degenerative arthritis. Hip/ knee replacement surgery in patients with skeletal dysplasia is a technically demanding exercise due to abnormal skeletal size and shape. Subluxation of the hips is a combination of femoral deformity, failure of epiphyseal ossification, acetabular dysplasia (failure of hip socket development), and joint contractures (flexion and adduction). A combination of femoral and pelvic osteotomies may be necessary. Since the femoral head is flattened, a valgus proximal femoral osteotomy is preferred to a varus procedure. If the hip joint is not congruous, acetabular augmentation procedures (Chiari osteotomy or Shelf procedure) are used to salvage the hip.

 
Problems Elsewhere in Body

Few problems, if any, occur and good general health can be expected.

 
What to Watch For

Pseudoachondroplastic patients should look out for neurological symptoms such as weakness of the lower limbs, incontinence, pain in the legs, reduced endurance, and tingling/ numbness of the legs. These symptoms may indicate compression of the spinal cord in the neck.

Lower extremity pain of gradual onset or changes in walking (waddling/ limping) may also result from altered alignment of the legs. In later life, pain in the hips and knees is usually the result of degenerative arthritis.

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.

 
References
  1. Jones, Kenneth L. Recognizable Patterns of Human Malformation. Philadelphia, PA: Elsevier Saunders. 2006.
  2. Posey, Karen L. Hayes, Elizabeth. Haynes, Richard. Hecht, Jacqueline T. 2004. Role of TSP-5/COMP in Pseudoachondroplasia. The International Journal of Biochemistry and Cell Biology. 36: 1005-1012.
  3. Scott, Charles I. Dwarfism. Clinical Symposium, 1988; 40(1);11-14.
  4. Spranger, Jurgen W. Brill, Paula W. Poznanski, Andrew. Bone Dysplasias: An Atlas of Genetic Disorder of Skeletal Development. Oxford: Oxford University Press. 2002.

Trusted Insights from Nemours' KidsHealth

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, diet questionnaires, and family history tracking — each helps to assess the health of you and your baby, and to predict any potential health risks.

Unlike your parents, 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:

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 simplest 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 human chromosomes carry from 25,000 to 35,000 genes. 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. 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. For example, sometimes babies have been diagnosed with spina bifida before birth. Recent research suggests that delivering a baby with spina bifida via cesarean section (avoiding the trauma of travel through the birth canal) can minimize damage to the spine — and perhaps reduce the likelihood that the child will need a wheelchair.

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 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 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, or Middle Eastern descent may carry the gene for thalassemia, a red blood cell disorder.

Meeting With a Genetic Counselor

Before you meet with a genetic counselor in person, you'll 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.

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 often will encourage you to come in for a discussion.

The counselor will study your records before meeting with you, so you can make the best use of your time together. During the session, 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.

After Counseling

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 prior to 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
  • adoption
  • 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 good 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 with whom they work. You can also contact the National Society of Genetic Counselors for more information.

Reviewed by: Louis E. Bartoshesky, MD, MPH
Date reviewed: June 2010
Originally reviewed by: Linda Nicholson, MS, MC