Platyspondylic lethal skeletal dysplasia Torrance type

Alternate names

PLSDT; Lethal short-limbed platyspondylic dwarfism Torrance type; Thanatophoric dysplasia torrance variant

Definition

Platyspondylic lethal skeletal dysplasia, Torrance type is a severe disorder of bone growth. People with this condition have very short arms and legs, underdeveloped pelvic bones, and unusually short fingers and toes (brachydactyly).

Epidemiology

This condition is very rare; only a few affected individuals have been reported worldwide.

Cause

• Platyspondylic lethal skeletal dysplasia, Torrance type is one of a spectrum of skeletal disorders caused by mutations in the COL2A1 gene.
• This gene provides instructions for making a protein that forms type II collagen.
• This type of collagen is found mostly in the clear gel that fills the eyeball (the vitreous) and in cartilage.
• Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development.
• Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears.
• Type II collagen is essential for the normal development of bones and other connective tissues that form the body's supportive framework.

Gene mutations

• All of the COL2A1 mutations that have been found to cause platyspondylic lethal skeletal dysplasia, Torrance type occur in a region of the protein called the C-propeptide domain.
• These mutations interfere with the assembly of type II collagen molecules, reducing the amount of this type of collagen in the body.
• Instead of forming collagen molecules, the abnormal COL2A1 protein builds up in cartilage cells (chondrocytes).
• These changes disrupt the normal development of bones and other connective tissues, leading to the skeletal abnormalities characteristic of platyspondylic lethal skeletal dysplasia, Torrance type.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Signs and symptoms

• This disorder is also characterized by flattened spinal bones (platyspondyly) and an exaggerated curvature of the lower back (lordosis).
• Infants with this condition are born with a small chest with short ribs that can restrict the growth and expansion of the lungs.
• As a result of these serious health problems, some affected fetuses do not survive to term.
• Infants born with platyspondylic lethal skeletal dysplasia, Torrance type usually die at birth or shortly thereafter from respiratory failure.
• A few affected people with milder signs and symptoms have lived into adulthood.

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

• Abdominal distention(Abdominal bloating)
• Abnormality of the carpal bones
• Disproportionate short-limb short stature(Short limb dwarfism, disproportionate)
• Hypoplasia of the capital femoral epiphysis(Small innermost thighbone end part)
• Hypoplastic pelvis
• Metaphyseal cupping
• Micromelia(Smaller or shorter than typical limbs)
• Narrow chest(Low chest circumference)
• Platyspondyly(Flattened vertebrae)
• Short distal phalanx of finger(Short outermost finger bone)
• Short foot(Short feet)
• Short palm
• Short thorax(Shorter than typical length between neck and abdomen)
• Skeletal dysplasia

30%-79% of people have these symptoms

• Depressed nasal bridge(Depressed bridge of nose)
• Genu varum(Outward bow-leggedness)
• Hydrops fetalis
• Hypoplastic scapulae(Small shoulder blade)
• Low-set ears(Low set ears)
• Malar flattening(Zygomatic flattening)
• Polyhydramnios(High levels of amniotic fluid)
• Prominent forehead(Pronounced forehead)
• Pulmonary hypoplasia(Small lung)

5%-29% of people have these symptoms

• Cleft palate(Cleft roof of mouth)

NIH genetic and rare disease info

• NIH info on Platyspondylic lethal skeletal dysplasia Torrance type

Platyspondylic lethal skeletal dysplasia Torrance type is a rare disease.