Brachyolmia type 3

Alternate names

Brachyolmia autosomal dominant; Brachyrachia; Autosomal dominant brachyolmia

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.

Cause

• 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 .
• 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.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

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

Signs and symptoms

• 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.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Increased vertebral height
• Kyphoscoliosis
• Platyspondyly(Flattened vertebrae)
• Short stature(Decreased body height)
• Short thorax(Shorter than typical length between neck and abdomen)

5%-29% of people have these symptoms

• Abnormality of the metaphysis(Abnormality of the wide portion of a long bone)

Diagnosis

The diagnosis of an autosomal dominant TRPV4 disorder is established in a proband with characteristic clinical and neurophysiologic findings, radiographic findings in the skeletal dysplasias, and a heterozygous TRPV4 pathogenic variant identified on molecular genetic testing.

Treatment

• Treatment is focused on symptom management.
• Affected individuals are often evaluated and managed by a multidisciplinary team that may include neurologists, physiatrists, orthopedic surgeons, and physical and occupational therapists.
• SNHL is managed by specialists to determine the best management options.

For neuromuscular disorders, neuropathy and respiratory dysfunction are managed in a routine manner; individuals with laryngeal dysfunction require ENT evaluation that should include speech therapy, laryngoscopy, and, in some instances, surgery.

For skeletal dysplasias, physical therapy/exercise and heel-cord stretching to maintain function; surgical intervention when kyphoscoliosis compromises pulmonary function and/or causes pain and/or when upper cervical spine instability and/or cervical myelopathy are present.[1].

NIH genetic and rare disease info

• NIH info on Brachyolmia type 3

Brachyolmia type 3 is a rare disease.

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