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Disease Profile

Brachyolmia type 3

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.

Unknown

Age of onset

Childhood

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ICD-10

Q76.3

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.

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)

Brachyolmia autosomal dominant; Brachyrachia; Autosomal dominant brachyolmia

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
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Orpha Number: 93304

Definition
A relatively severe form of brachyolmia, a group of rare genetic skeletal disorders, characterized by short-trunked short stature, platyspondyly and kyphoscoliosis. Degenerative joint disease (osteoarthropathy) in the spine, large joints and interphalangeal joints becomes manifest in adulthood.

Epidemiology
The precise prevalence of this form of brachyolmia is not known. About 30 cases have been reported.

Clinical description
Patients with Brachyolmia type 3 generally have a normal birth weight and length. Affected individuals present with moderately short trunk/short stature and mildly short limbs in childhood. Kyphoscoliosis is common and sometimes severe. Adult patients develop degenerative joint disease in the spine, large joints and small joints of the hands and feet, which may cause significant musculoskeletal morbidity, such as chronic pain in the extremities and spine, and paresthesia. Final adult height is reported to be 155-168 cm (males) and 136-150 cm (females). The radiographic features include severe platyspondyly particularly in the cervical spine, elongated vertebral bodies (overfaced pedicles), broad ilia, and mild metaphyseal irregularity in the proximal femora. Carpal ossification may be mildly delayed, and mild brachydactyly may exist.

Etiology
Heterozygous mutations in the TRPV4 gene (12q24.11) are responsible for autosomal dominant brachyolmia. TRPV4 mutations are associated with other skeletal dysplasias, including lethal and nonlethal metatropic dysplasia, spondyloepiphyseal dysplasia Maroteaux type, and spondylometaphyseal dysplasia Kozlowski type (see these terms). Autosomal dominant brachyolmia falls into the mildest end of the TRPV4-associated skeletal dysplasia group. TRPV4 encodes a Ca-permeable, non-selective cation channel that participates in the regulation of osmotic sensitivity and mechanosensitivity. It remains to be explained how dysregulation of the cation channel causes the skeletal abnormalities.

Genetic counseling
Genetic counseling should be provided to affected families, in consideration of the autosomal dominant mode of inheritance.

Visit the Orphanet disease page for more resources.

Symptoms

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
Increased vertebral height
0004570
Kyphoscoliosis
0002751
Platyspondyly
Flattened vertebrae
0000926
Short stature
Decreased body height
Small stature

[ more ]

0004322
Short thorax
Shorter than typical length between neck and abdomen
0010306
5%-29% of people have these symptoms
Abnormality of the metaphysis
Abnormality of the wide portion of a long bone
0000944
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Barrel-shaped chest
Barrel chest
0001552
Childhood-onset short-trunk short stature
Disproportionate short-trunk short stature, identifiable in childhood
Short-trunk dwarfism identifiable during childhood

[ more ]

0008922
Clinodactyly
Permanent curving of the finger
0030084
Hypermetropia
Farsightedness
Long-sightedness

[ more ]

0000540
Kyphosis
Hunched back
Round back

[ more ]

0002808
Proximal femoral metaphyseal irregularity
0003411
Radial deviation of finger
0009466
Scoliosis
0002650
Short femoral neck
Short neck of thighbone
0100864
Short neck
Decreased length of neck
0000470
Spinal cord compression
Pressure on spinal cord
0002176

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      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 Brachyolmia type 3. Click on the link to view a sample search on this topic.