Primordial Dwarfism
What does the name mean?
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).
What conditions make up the class of primordial dwarfism?
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:
These 5 conditions are:
- Majewski Osteodysplastic Primordial Dwarfism Type I (MOPD I)
- Majewski Osteodysplastic Primordial Dwarfism Type II (MOPD II)
- Majewski Osteodysplastic Primordial Dwarfism Type III (MOPD III)
- Russell Silver Syndrome
- Seckel Syndrome
- Meier-Gorlin Syndrome
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 are quite rare and very little is known concerning the incidences. For MOPD Type II, estimates that there are no more than 100 patients in the United States and Canada giving a rough estimate of 1 in 3 million.
Here in the UK, there are now an estimated 12 cases which gives a estimate of 1 in 5 million.
There are known cases in Germany, Slovenia, India, Saudia Arabia, Austrialia, New Zealand and South America.
Is MOPD Type II inherited?
The precise gene for MOPD II and inheritance pattern of MOPD Type II is unknown, but most data suggest that it follows an autosomal recessive pattern. There are several sibling pairs born to parents of average stature.
What causes MOPD Type II ?
Simply put, the underlying cause is unknown.
What are the physical characteristics of Primordial Dwarfism?
Below are 5 photographs of individuals with MOPD II.
 |
 |
||
 |
 |
||
Probably the most consistent physical characteristic in these 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 typically weigh less than 3 lbs and are less than 16 inches in length. Most children however are born slightly premature at 35 weeks with an average birth weight of 2 lbs 3 oz. This is about the average size of a 28 week premature neonate. Adult heights are typically less than 33 inches and the voice is high pitched.
In theory individuals individuals affected by MOPD II are classified by many as the smallest people in the world. Some individuals have not grown more than 19 inches.
To get a full understanding on how small the individuals in the pictures are, have a look at some of the following pointers :
- The top left picture shows Liam (aged 3 as of March 2008 standing at a toy rocking bull. He is 2ft 5ins. This toy is for children up to the ages 4+. As you can see from Liams height, he will need to jump up a bit to sit on it. Also have a look at the chair just at the back of the bull to the right. Small isn't it???
- The top right picture shows Finn (aged 3 as of March 2008) carrying her doll. Mothers who have young daughters will know how small these dolls are (9-10 inches). Finn is 2ft 1in and will possibly for the rest of her life!.
- The centre picture shows Alex and Gabe. At the time this photo was taken (Feb 2008), Alex was 34 months and Gabe was 8 months. Alex is 2ft 6ins at the moment and weighs 13lb 7oz. Compare Alex's head and hand sizes to Gabe's.
- The bottom left hand picture shows Rayth sitting in a pram, he shares the same birthday as Alex. He's 2ft 7ins. Do you think the pram will outgrow him???
- The bottom right hand picture is of Stephanie, she 2ft 9ins, she weighs 24lb - can you tell her age? she is 10!
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.
Trunk, Chest and Spine:
- Proportionately small trunk, chest, and spine.
- Scoliosis and thoracic kyphosis in later childhood
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.
- Lumbar lordosis, as a consequence of coxa vara.
- Ligamentous laxity develops with age
Other characteristics:
- Fine and relatively sparse hair.
- Pigmentary dysplasia of the skin.
What are the x-ray characteristics?
In the newborn, the x-rays typically do not demonstrate major structural abnormalities, although the pelvis is narrow with small wings and flattened acetabular angles. The long bones may be overtubulated. Eleven rib pairs are sometimes seen, rather than twelve. As the children 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.
How is the diagnosis made?
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.
What are the associated medical problems?
- Nutrition- Most infants with primordial dwarfism have feeding problems. Small volumes and frequent feeding are typical. Sometimes naso-gastric feeding or g-tube feedings are needed.
- Brain- About 25% of 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.
What are things to watch out for?
- 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.
- About 20% of patients have had abnormalities in the cerebral vascular system which can predispose to stroke. Children with MOPD II should have monitoring of their cerebral vascular systems by MRI / MRA.
- There is no evidence of growth hormone deficiency nor is a response to treatment seen in MOPD II patients. However, in some cases an initial small spurt in growth can be seen, but does not appear to persist.
References
1. Most of the above can be examinsed more closely in the following document:
Majewski osteodysplastic primordial dwarfism type II (MOPD II): natural history and clinical findings. Hall JG, Flora C, Scott CI Jr, Pauli RM, Tanaka KI. Am J Med Genet A. 2004 Sep 15;130(1):55-72.
2: The majority of the above contents has been used with kind permission of:
Dr Michael Bober MD PhD
Geneticist
Co-Director - Skeletal Dysplasia Program
Alfred I. duPont Hospital for Children
1600 Rockland Road
P.O. Box 269
Wilmington, DE 19899
www.nemours.org/hospital/de/aidhc.html
The orginal summary information can be found at:
2: Some of the content has been added by myself, John Connerty (Alex's Dad).
Disclaimer
Please note the above does not replace individual medical advice or provides a diagnosis. If any parent or guardian visiting this site thinks their child has a form of Primordial Dwarfism, they should consult a local Clinical Geneticist or ask their local pediatrician/doctor to make a referral.
A list of regional Genetics Centres in the UK can be found by visiting the link on the right.