Primordial has been defined as belonging to or being characteristic of the earliest stages of development of an organism. Therefore, Primordial Dwarfism is a class of disorders where growth delay occurs at the earliest stages of development. Unlike some of the other forms of dwarfism where newborn infants can have average lengths, children with Primordial Dwarfism are born smaller than average and have intrauterine growth retardation (IUGR).
Unlike some of the other conditions described on this website, primordial dwarfism is not a specific diagnosis.
It is in fact a class of disorders to which at least 5 different conditions are currently grouped:
- Russell-Silver syndrome
- Seckel syndrome
- Meier-Gorlin syndrome
- Majewski osteodysplastic primordial dwarfism (MOPD) Types I/III
- MOPD Type II
The Russell-Silver, Seckel and Meier-Gorlin syndromes are relatively well defined entities and we will not discuss them here.
We will limit our discussion to MOPD Type II. Most of the information below can be examined in more detail in Hall et. al (1).
All of the conditions that make up primordial dwarfism are quite rare and very little is known concerning the incidences. For MOPD Type II, we estimate that there are no more than 100 patients in the United States and Canada giving a rough estimate of 1 in 3 million.
Everyone has two copies of a gene called pericentrin (PCNT). MOPDII results when there is a gene change (mutation) in each copy of an individual’s pericentrin gene, causing both copies to be nonfunctional (2).
Probably the most consistent physical characteristic of primordial dwarfism in children is severe intrauterine growth retardation (IUGR). Recognition of the deficiency can occur as early as 13-weeks gestation and it becomes progressively more severe over the length of the pregnancy.
At term, infants with primordial dwarfism typically weigh less than 3 lbs and are less than 16 inches in length. This is about the average size of a 28-week premature neonate. However, some children with genetically confirmed MOPDII have been born larger than this. Adult heights are typically less than 33" and the voice is high pitched.
Face and Skull
- Microcephaly. Head size is proportionate to body size at birth. However, as children grow and develop, the head grows slower than the body and becomes disproportionately small.
- Premature closure of the soft spots (fontanelles) and craniosynostosis
- Prominent nose and eyes. The conspicuous nose may be obvious at birth or it may develop over the first year.
- Small teeth with deficient enamel and increased spaces between them. Small roots in the secondary teeth. Secondary teeth can be missing or lost prematurely.
Arms and Legs:
- disproportionately short forearm in childhood, causing mesomelia
- dislocated radial head with decreased range of motion at the elbows
- dislocated hips and coxa vara at birth
- ligamentous laxity develops with age
Other Characteristics of Primordial Dwarfism:
- fine and relatively sparse hair
- pigmentary changes of the skin, such as acanthosis nigricans
What are the X-Ray Characteristics of Primordial Dwarfism?
In newborns with primordial dwarfism, the X-rays typically do not demonstrate major structural abnormalities, although the pelvis is narrow with small iliac wings and flattened acetabular angles. The long bones may be overtubulated. Eleven rib pairs are sometimes seen, rather than twelve. As children with primordial diagnosis age, the bones appear thin and delicate with progressive metaphyseal widening at the ends of the long bones.
Bone age studies usually show decreased bone age; that is, the skeletal maturation process is slowed in these children and can be delayed 2–5 years behind the actual age.
The differential diagnosis for MOPD II is complex and is done clinically based upon history, physical characteristics, radiographic review and the exclusion of any other physical findings or laboratory abnormalities.
There is also research genetic testing available either through Texas
or Scotland that can help confirm what type of primordial dwarfism an individual has.
Most infants with primordial dwarfism have feeding problems, but it is important that the treating physician lower their expectations of daily growth to at least half that of a typical child.
Small volumes and frequent feeding are typical. Sometimes nasogastric feeding or g-tube feedings are used.
Some patients have structural or myelination abnormalities in the brain. Structural abnormalities have included: enlarged ventricles, abnormal gyral patterns and abnormal corpus callosum.
Precocious puberty has been described in girls with breast development as early as 7 and menarche, or the beginning of periods, at 9 years. Boys do not seem to have precocious puberty.
Renal or kidney anomalies have been described and a renal ultrasound should be done as the diagnosis is being established.
Most of the patients develop farsightedness which requires glasses. Careful ophthalmologic evaluation is indicated at regular intervals.
A vast majority of individuals with MOPDII have had abnormalities in the cerebral vascular system, including moyamoya disease and aneurysms, which can predispose to stroke. Screenings with MRA/CTA of the brain should begin at diagnosis of MOPDII and continue every 12 to 18 months thereafter to permit early detection of these conditions. If diagnosed in the early stages, revascularization and aneurysm treatment can be performed safely and effectively. (3)
Insulin resistance is associated with MOPDII and can often progress to frank diabetes. Yearly screening labs should begin by 5 years of age and include: hemoglobin A1C, insulin levels, fasting blood sugars, liver functions and lipid profiles. The physician should maintain a high degree of suspicion and if any signs or symptoms develop, further testing is indicated. If changes are present, appropriate follow-up and management plans can be implemented. It does appear that these patients respond well to an oral antihyperglycemic medication like metformin. (4)
A yearly CBC should also be obtained as some children, especially post-pubertal girls, have developed anemia. Furthermore, it does appear that baseline platelet counts may be elevated. The clinical significance of this remains to be determined.
- Hall JG, Flora C, Scott CI Jr., Pauli RM, Tanaka KI. Majewski osteodysplastic primordial dwarfism type II (MOPDII): natural history and clinical findings. Am J Med Genet A. 2004 Sep 15;130A(1):55-72.
- Rauch A, Thiel CT, Schindler D, Wick U, Crow YJ, Ekici AB, van Essen AJ, Goecke TO, Al-Gazali L, Chrzanowska KH, Zweier C, Brunner HG, Becker K, Curry CJ, Dallapiccola B, Devriendt K, Dörfler A, Kinning E, Megarbane A, Meinecke P, Semple RK, Spranger S, Toutain A, Trembath RC, Voss E, Wilson L, Hennekam R, de Zegher F, Dörr HG, Reis A. Mutations in the pericentrin (PCNT) gene cause primordial dwarfism. Science. 2008 Feb 8; 319(5864):816-9.
- Bober MB, Khan N, Kaplan J, Lewis K, Feinstein JA, Scott CI Jr, Steinberg GK. Majewski osteodysplastic primordial dwarfism type II (MOPD II): expanding the vascular phenotype. Am J Med Genet A. 2010 Apr;152A(4):960-5.
- Huang-Doran I, Bicknell LS, Finucane FM, Rocha N, Porter KM, Tung YC, Szekeres F, Krook A, Nolan JJ, O'Driscoll M, Bober M, O'Rahilly S, Jackson AP, Semple RK; for the Majewski Osteodysplastic Primordial Dwarfism Study Group. Genetic Defects in Human Pericentrin Are Associated With Severe Insulin Resistance and Diabetes. 2011 Mar;60(3):925-35. Epub 2011 Jan 26.
From Nemours' KidsHealth
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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