Metatropic dysplasia

Alternate names

Metatropic dwarfism; Metatropic dysplasia, nonlethal dominant

Definition

Metatropic dysplasia is a skeletal disorder characterized by short stature, shortened arms and legs, and a long narrow chest.

The term "metatropic" is derived from the Greek word "metatropos," which means "changing patterns." This name reflects the fact that the skeletal abnormalities associated with the condition change over time.

Epidemiology

Metatropic dysplasia is a rare disease; its exact prevalence is unknown. More than 80 affected individuals have been reported in the scientific literature.

Cause

• Metatropic dysplasia is caused by mutations in the TRPV4 gene, which provides instructions for making a protein that acts as a calcium channel.
• The TRPV4 channel transports positively charged calcium atoms (calcium ions) across cell membranes and into cells.
• The channel is found in many types of cells, but little is known about its function.
• Studies suggest that it plays a role in the normal development of cartilage and bone.
• This role would help explain why TRPV4 gene mutations cause the skeletal abnormalities characteristic of metatropic dysplasia.

Gene mutations

• Mutations in the TRPV4 gene appear to overactivate the channel, increasing the flow of calcium ions into cells.
• However, it remains unclear how changes in the activity of the calcium channel lead to the specific features of the condition.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

• Metatropic dysplasia is considered an autosomal dominant disorder because one mutated copy of the TRPV4 gene in each cell is sufficient to cause the condition. Most cases of metatropic dysplasia are caused by new mutations in the gene and occur in people with no history of the disorder in their family. In a few reported cases, an affected person has inherited the condition from an affected parent.
• In the past, it was thought that the lethal type of metatropic dysplasia had an autosomal recessive pattern of inheritance, in which both copies of the gene in each cell have mutations. However, more recent research has confirmed that all metatropic dysplasia has an autosomal dominant pattern of inheritance.

Signs and symptoms

Metatropic dysplasia is a bone disorder with symptoms recognizable in infancy including short stature, a narrow chest with short ribs, and shortened arms and legs with "telephone" shaped long bones.

Other signs and symptoms may include:

• Joint restriction and contractures
• Issues with the spine such as abnormal curvature (scoliosis and kyphosis), a long coccyx, and flattening of the bones of the spine (platyspondyly)
• An abnormally shaped pelvis
• Different facial features such as a prominent forehead, underdevelopment of the upper jaw, cheekbones and eye sockets (midface hypoplasia), and a squared-off jaw
• Shortening of the fingers and toes (brachydactyly)
• Damage to certain nerves in the body
• Arthritis
• Breathing issues due to spine, chest, and rib abnormalities

Clinical presentation

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

• Abnormal cortical bone morphology
• Abnormal enchondral ossification
• Abnormal form of the vertebral bodies
• Abnormality of the intervertebral disk
• Abnormality of the ribs(Rib abnormalities)
• Coarse metaphyseal trabecularization
• Depressed nasal bridge(Depressed bridge of nose)
• Halberd-shaped pelvis
• High forehead
• Hypoplastic cervical vertebrae
• Joint stiffness(Stiff joint)
• Kyphosis(Hunched back)
• Long thorax(Long rib cage)
• Micromelia(Smaller or shorter than typical limbs)
• Narrow chest(Low chest circumference)
• Scoliosis
• Severe short stature(Dwarfism)
• Skeletal dysplasia

5%-29% of people have these symptoms

• Aplasia/Hypoplasia of the lungs(Absent/small lungs)
• Camptodactyly of finger(Permanent flexion of the finger)
• Cataract(Clouding of the lens of the eye)
• Cleft palate(Cleft roof of mouth)
• Clinodactyly of the 5th finger(Permanent curving of the pinkie finger)
• Fetal akinesia sequence
• Flexion contracture(Flexed joint that cannot be straightened)
• Hydrocephalus(Too much cerebrospinal fluid in the brain)
• Low-set, posteriorly rotated ears
• Peripheral axonal neuropathy

1%-4% of people have these symptoms

• Arthrogryposis multiplex congenita

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.<ref>McCray BA, Schindler A, Hoover-Fong JE, et al. Autosomal Dominant TRPV4 Disorders. 2014 May 15 [Updated 2020 Sep 17]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK201366/ </ref>[1].

Treatment

• Treatment of this condition focuses on managing the skeletal concerns and maintaining the functioning of the lungs.
• Treatment may include the use of braces, physical therapy, and surgical correction of skeletal abnormalities.

References

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NIH genetic and rare disease info

• NIH info on Metatropic dysplasia

Metatropic dysplasia is a rare disease.

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