Primordial Dwarfism

Five children with primordial dwarfism

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).

 
Conditions Making Up the Class of Primordial Dwarfism

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).

 
How Common Is Primordial Dwarfism?

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.

 
How MOPD Type II Is Inherited

MOPDII has an autosomal recessive pattern. This means that the genetic information from both parents was necessary for the child to have this condition. This means that the genetic information from both parents was necessary for the child to have primordial dwarfism.

 
Causes of MOPD Type II

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).

 
Physical Characteristics of Primordial Dwarfism

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 & 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.
Trunk, Chest, & Spine:
  • Proportionately small trunk, chest, and spine
  • Scoliosis and thoracic kyphosis in later childhood
Arms & 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.

 
Diagnosing Primordial Dwarfism

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.

 
Medical Problems Associated With Primordial Dwarfism
Nutrition

Most infants with primordial dwarfism have feeding problems, but it is important that the treating physican lower their expectations of daily growth to at least half that of a typical child.

Small volumes and frequent feeding are typical. Sometimes naso-gastric feeding or g-tube feedings are used.

Brain

Some patients have structural or myelination abnormalities in the brain. Structural abnormalities have included: enlarged ventricles, abnormal gyral patterns and abnormal corpus callosum.

Development

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.

 
Recommended Monitoring

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.

 
References
  1. 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.
  2. 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.
  3. 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.
  4. 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.

Trusted Insights from Nemours' KidsHealth

Dwarfism

There's been a lot of discussion over the years about the proper way to refer to someone with dwarfism. Many people who have the condition prefer the term "little person" or "person of short stature." For some, "dwarf" is acceptable. For most, "midget" definitely is not.

But here's an idea everyone can agree on: Why not simply call a person with dwarfism by his or her name?

Being of short stature is only one of the characteristics that make a little person who he or she is. If you're the parent or loved one of a little person, you know this to be true.

But here are some facts that other people may not realize about dwarfism and those who have it.

Dwarfism:

  • is characterized by short stature. Technically, that means an adult height of 4 feet 10 inches or under, according to the advocacy group Little People of America (LPA).
  • can be caused by any one of more than 300 conditions, most of which are genetic. The most common type, accounting for 70% of all cases of short stature, is called achondroplasia.
  • can and most often does occur in families where both parents are of average height. In fact, 4 out of 5 of children with achondroplasia are born to average-size parents.

Dwarfism isn't:

  • an intellectual disability. A person who has dwarfism is typically of normal intelligence.
  • a disease that requires a "cure." Most people with one of these conditions live long, fulfilling lives.
  • a reason to assume someone is incapable. Little people go to school, go to work, marry, and raise children, just like their average-size peers.

What Causes Short Stature?

More than 300 well-described conditions are known to cause short stature in a child. Most are caused by a spontaneous genetic change (mutation) in the egg or sperm cells prior to conception. Others are caused by genetic changes inherited from one or both parents.

Similarly, depending on the type of condition causing the short stature, it is possible for two average-size parents to have a child with short stature, and is also possible for parents who are little people to have an average-size child.

What prompts a gene to mutate is not yet clearly understood. The change is seemingly random and unpreventable, and can occur in any pregnancy. If parents have some form of dwarfism themselves, the odds are much greater that their children will also be little people. A genetic counselor can help determine the likelihood of passing on the condition in these cases.

Dwarfism has other causes, including metabolic or hormonal disorders in infancy or childhood. Chromosomal abnormalities, pituitary gland disorders (which influence growth and metabolism), absorptive problems (when the body can't absorb nutrients adequately), and kidney disease can all lead to short stature if a child fails to grow at a normal rate.

Types of Short Stature

Most types of dwarfism are known as skeletal dysplasias, which are conditions of abnormal bone growth. They're divided into two types: short-trunk and short-limb dysplasias. People with short-trunk dysplasia have a shortened trunk with more average-sized limbs, whereas those with short-limb dysplasia have an average-sized trunk but shortened arms and legs.

By far, the most common skeletal dysplasia is achondroplasia, a short-limb dysplasia that occurs in about 1 of every 15,000 to 40,000 babies born of all races and ethnicities. It can be caused by a spontaneous mutation in a gene called FGFR3, or a child can inherit a change in this gene from a parent who also has achondroplasia.

People with achondroplasia have a relatively long trunk and shortened upper parts of their arms and legs. They may share other features as well, such as a larger head with a prominent forehead, a flattened bridge of the nose, shortened hands and fingers, and reduced muscle tone. The average adult height for someone with achondroplasia is a little over 4 feet.

Diastrophic dysplasia is a different form of short-limb dwarfism. It occurs in about 1 in 100,000 births, and is also sometimes associated with cleft palate, clubfeet, and ears with a cauliflower-like appearance. People who have this diagnosis tend to have shortened forearms and calves (this is known as mesomelic shortening).

Spondyloepiphyseal dysplasias (SED) refers to a group of various short-trunk skeletal conditions that occurs in about 1 in 95,000 babies. Along with achondroplasia and diastrophic dysplasia, it is one of the most common forms of dwarfism. In some forms, a lack of growth in the trunk area may not become apparent until the child is between 5 and 10 years old; other forms are apparent at birth. Kids with this disorder also might have clubfeet, cleft palate, and a barrel-chested appearance.

In general, dwarfism caused by skeletal dysplasias results in what is known as disproportionate short stature — meaning the limbs and the trunk are not the same proportionally as those of typically-statured people.

Metabolic or hormonal disorders typically cause proportionate dwarfism, meaning a person's arms, legs, and trunk are all shortened but remain in proportion to overall body size.

Diagnosis

Some types of dwarfism can be identified through prenatal testing if a doctor suspects a particular condition and tests for it.

But most cases are not identified until after the child is born. In those instances, the doctor makes a diagnosis based on the child's appearance, failure to grow, and X-rays of the bones. Depending on the type of dwarfism the child has, diagnosis often can be made almost immediately after birth.

Once a diagnosis is made, there is no "treatment" for most of the conditions that lead to short stature. Hormonal or metabolic problems may be treated with hormone injections or special diets to spark a child's growth, but skeletal dysplasias cannot be "cured."

People with these types of dwarfism can, however, get medical care for some of the health complications associated with their short stature.

Some forms of dwarfism also involve issues in other body systems — such as vision or hearing — and require careful monitoring.

Possible Complications and Treatments

Short stature is the one quality all people with dwarfism have in common. After that, each of the many conditions that cause dwarfism has its own set of characteristics and possible complications.

Fortunately, many of these complications are treatable, so that people of short stature can lead healthy, active lives.

For example, a small percentage of babies with achondroplasia may experience hydrocephalus (excess fluid around the brain). They may also have a greater risk of developing apnea — a temporary stop in breathing during sleep — because of abnormally small or misshapen anatomy or, more likely, because of airway obstruction by the adenoids or the tonsils. Occasionally, a part of the brain or spinal cord is compressed. With close monitoring by doctors, however, these potentially serious problems can be detected early and surgically corrected.

As a child with dwarfism grows, other issues may also become apparent, including:

  • delayed development of some motor skills, such as sitting up and walking
  • a greater susceptibility to ear infections and hearing loss
  • breathing problems caused by small chests
  • weight problems
  • curvature of the spine (scoliosis, kyphosis, and/or lordosis)
  • bowed legs
  • trouble with joint flexibility and early arthritis
  • lower back pain or leg numbness
  • crowding of teeth in the jaw

Proper medical care can alleviate many of these problems. For example, surgery often can bring relief from the pain of joints that wear out under the stress of bearing weight differently with limited flexibility.

Surgery also can be used to improve some of the leg, hip, and spine problems people with short stature sometimes face.

Nonsurgical options may help, too — for instance, excessive weight can worsen many orthopedic problems, so a nutritionist might help develop a healthy plan for shedding extra pounds. And doctors or physical therapists can recommend ways to increase physical activity without putting extra stress on the bones and joints.

Helping Your Child

Although types of dwarfism, and their severity and complications, vary from person to person, in general a child's life span is not affected by dwarfism. Although the Americans with Disabilities Act protects the rights of people with dwarfism, many members of the short-statured community don't feel that they have a disability.

You can help your child with dwarfism lead the best life possible by building his or her sense of independence and self-esteem right from the start.

Here are some tips to keep in mind:

  • Treat your child according to his or her age, not size. If you expect a 6-year-old to clean up his or her room, don't make an exception simply because your child is small.
  • Adapt to your child's limitations. Something as simple as a light switch extender can give a short-statured child a sense of independence around the house.
  • Present your child's condition — both to your child and to others — as a difference rather than a hindrance. Your attitude and expectations can have a significant influence on your child's self-esteem.
  • Learn to deal with people's reactions, whether it's simple curiosity or outright ignorance, without anger. Address questions or comments as directly as possible, then take a moment to point out something special about your child. If your child is with you, this approach shows that you notice all the other qualities that make him or her unique. It will also help prepare your child for dealing with these situations when you're not there.
  • If your child is teased at school, don't overlook it. Talk to teachers and administrators to make sure your child is getting the support he or she needs.
  • Encourage your child to find a hobby or activity to enjoy. If sports aren't going to be your child's forte, then maybe music, art, computers, writing, or photography will be.
  • Finally, get involved with support associations like the Little People of America. Getting to know other people with dwarfism — both as peers and mentors — can show your child just how much he or she can achieve.

Reviewed by: Angela L. Duker, MS, CGC
Date reviewed: March 2011