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Disease Profile

Axial spondylometaphyseal dysplasia

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

Q77.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Axial SMD; Spondylometaphyseal dysplasia axial type; SMD Axial

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases

Summary

Axial spondylometaphyseal dysplasia is a genetic disorder of bone growth. The term “axial” means towards the center of the body. “Sphondylos” is a Greek term meaning vertebra. “Metaphyseal dysplasia” refers to abnormalities at the ends of long bones. Axial spondylometaphyseal dysplasia primarily affects the bones of the chest, pelvis, spine, upper arms and upper legs, and results in shortened stature. For reasons not well understood, this rare skeletal dysplasia is also associated with early and progressive vision loss. The underlying genetic cause of axial spondylometaphyseal dysplasia is currently unknown. It is thought to be inherited in an autosomal recessive fashion.[1]

Symptoms

Common signs and sympotms of axial spondylometaphyseal dysplasia, include short stature, chest, spine, limb, and pelvic bone changes, and vision disturbance.[1]

People with axial spondylometaphyseal dysplasia may have a normal birth length, but demonstrate growth failure by late infancy to early childhood. A measurement called standard deviation (SD) is used to compare the height of different children. If a child's height is more than 2 SD's below the average height of other children the same age, the child is said to have short stature. This means that almost all of the other children that age (more than 95% or 19 out of 20) are taller.[2] Individual case reports of children and an adult with axial spondlometaphyseal dysplasia demonstrate height as being between 2 to 6 SD’s below average.[1]

Infants with axial spondlometaphyseal dysplasia tend to have a shortened chest with short ribs, a condition called thoracic hypoplasia. Thoracic hypoplasia tends to become more prominent in childhood, and less noticeable in adolescence and adulthood. Thoracic hypoplasia may cause mild to moderate breathing problems in infants and recurring lung infections in childhood.[1]

Young children with axial spondlometaphyseal dysplasia have shortened upper arms and upper leg bones, which may become less prominent as they grow.[1]

Spine changes include vertebrae that have a flattened appearance on x-ray. This finding is typically mild in infancy and early childhood, becomes more apparent in late childhood, then self-corrects by adulthood. Some individuals with axial spondylometaphyseal dysplasia develop scoliosis (curvature of the spine).[1]

Pelvic bone changes can be seen in infants and children. Some of these changes self-correct by adulthood.[1] A condition called “coxa vara” (where the angle between the top of the femur and the femoral shaft is smaller than normal) is common beginning in late childhood and persists through adulthood.[1] Coxa vara may affect gait (pattern or way of walking). Some people with axial spondlometaphyseal dysplasia have minor bone changes in their knees.[1]

Vision problems, including retinitis pigmentosa and/or optic atrophy, become evident in infancy or early childhood and rapidly worsen.[1] Retinitis pigmentosa causes cells in the retina to breakdown and die, eventually resulting in vision loss. Optic atrophy causes vision to dim and reduces the field of vision. It also reduces the ability to see fine detail and color (ie., colors will seem faded). With the progression of optic atrophy, a person's pupil reaction to light diminishes and may eventually be lost. Long term outlook for vision for people with axial spondylometaphyseal dysplasia is poor.[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Cupped ribs
Rib cupping
0000887
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development

[ more ]

0002750
Platyspondyly
Flattened vertebrae
0000926
Rhizomelia
Disproportionately short upper portion of limb
0008905
Rod-cone dystrophy
0000510
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

0000505
30%-79% of people have these symptoms
Frontal bossing
0002007
Irregular iliac crest
0003796
Optic atrophy
0000648
Proximal femoral metaphyseal irregularity
0003411
Thoracic hypoplasia
Small chest
Small thorax

[ more ]

0005257
5%-29% of people have these symptoms
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

0000463
Astigmatism
Abnormal curving of the cornea or lens of the eye
0000483
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Photophobia
Extreme sensitivity of the eyes to light
Light hypersensitivity

[ more ]

0000613
Proptosis
Bulging eye
Eyeballs bulging out
Prominent eyes
Prominent globes
Protruding eyes

[ more ]

0000520
Short nose
Decreased length of nose
Shortened nose

[ more ]

0003196
Telecanthus
Corners of eye widely separated
0000506
1%-4% of people have these symptoms
Splenomegaly
Increased spleen size
0001744
Percent of people who have these symptoms is not available through HPO
Anterior rib cupping
0000907
Autosomal recessive inheritance
0000007
Coxa vara
0002812
Narrow greater sciatic notch
0003375
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Recurrent pneumonia
0006532
Reduced sperm motility
0012207
Retinal degeneration
Retina degeneration
0000546
Short femoral neck
Short neck of thighbone
0100864
Short stature
Decreased body height
Small stature

[ more ]

0004322
Spondylometaphyseal dysplasia
0002657

Treatment

There is no specific treatment for axial spondylometaphyseal dysplasia. Symptoms such as lung infections, breathing difficulties, coxa vara, scoliosis, retinitis pigmentosa, and optic atrophy are managed individually. Specialists such as opthmologists, geneticists, and orthopedists work in concert in devloping an individualized treatment plan. We are unaware of any cases describing the use of growth hormone therapies for treatment of short stature caused by axial spondylometaphyseal dysplasia. Treatment of skeletal dysplasias with growth hormone therapy must be done with caution. 

The Little People of America, Inc Web site lists articles on repiratory and breathing problems in people with skeletal dysplasias, including an article titled Breathing Problems Among Little People: When to Be Concerned.

Detailed information related to the management of retinitis pigmentosa can be accessed through GeneReviews and the Treatment and Medication sections of Medscape Reference.

Detailed information related to the management of coxa vara can also be found in the Treatment sections of a Medscape Reference review article on this condition.

Johns Hopkins Department of Orthopedic Surgery offers a Patient Guide to Scoliosis.

MedlinePlus.gov provides information on optic atrophy

Further medical support resources can be found through the Little People of America, Inc.

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Axial spondylometaphyseal dysplasia. Click on the link to view a sample search on this topic.

    References

    1. Suzuki S, Kim OH, Makita Y, Saito T, Lim GY, Cho TJ, Al-Swaid A, Alrasheed S, Sadoon E, Miyazaki O, Nishina S, Superti-Furga A, Unger S, Fujieda K, Ikegawa S, Nishimura G. Axial spondylometaphyseal dysplasia: additional reports. Am J Med Genet A. 2011 Oct;155A(10):2521-8. Epub 2011 Sep 9; https://www.ncbi.nlm.nih.gov/pubmed/21910225. Accessed 9/14/2012.
    2. Short Stature. MedlinePlus. https://www.nlm.nih.gov/medlineplus/ency/article/003271.htm. Accessed 9/14/2012.

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