What are skeletal dysplasias

Skeletal dysplasias are a complex group of bone and cartilage disorders that may affect the fetal skeleton as it develops in utero.

Although each skeletal dysplasia is individually rare, they collectively affect one in every 4,000-5,000 births. The incidence of skeletal dysplasias may be higher since the symptoms may not manifest until early childhood, when short stature, joint abnormalities or other complications arise.

Symptoms of skeletal dysplasia

To date, more than 450 distinct skeletal disorders have been described which may result in numerous anomalies in the shape and size of the skeleton.

Some common symptoms of skeletal dysplasias include:

• Shortening in the bones of the legs and/or arms
• Bowed or fractured bones
• A small thorax
• Abnormal ribs
• Absence of a limb
• Asymmetric bone growth (e.g., one leg is longer than the other)
• Duplicated or missing fingers or toes
• Irregular, thickened or thin bones
• Demineralization 

Distinct skeletal disorders are identified by a common grouping of symptoms and characteristics. Common skeletal dysplasias and associated symptoms include:

• Thanatophoric dysplasia is typically characterized by abnormal shortness of limbs; a bowed femur (thigh bone) or other bones of the extremities; a small chest; thickened soft tissues; flattened vertebrae; unusually prominent forehead and depressed nasal bridge; and Cloverleaf skull (type II).
• Campomelic dysplasia is generally associated with a bowed femur (thigh bone) or other bones of the extremities; shortened limbs clubfeet; missing ribs; ambiguous genitalia; flattened facial features; a small jaw; and an unusually prominent forehead.
• Achondroplasia is characterized by shortened limbs, short forearms and lower legs; stubby fingers unusually prominent forehead; and abnormally decreased distance of the lumbar vertebrae in the lower back.
• Osteogenesis imperfecta typically includes fractures; bowed, irregular thickened bones; short/normal size extremities; soft, thin skull; and slender ribs.
• Achondrogenesis presents with thickened soft tissues; short limbs; bones of the spine that are not mineralized or fully formed; and a small thorax.

What causes skeletal dysplasia?

The causes of skeletal dysplasias are nearly as diverse as the number of distinct disorders. Generally, however, the causes can be cataloged into three groups:

• Genetically inherited as dominant or recessive traits or X-linked disorders
• The result of spontaneous mutations that are de novo, or "brand new" in the fetus
• Secondary to exposure to a toxic substance or infectious agent that results in the disruption of normal skeletal development 

Over half of the documented skeletal dysplasias are caused by a genetic mutation in a known gene that makes prenatal diagnosis possible through genetic testing. To date, over 500 genes have been identified to cause skeletal dysplasias.

Evaluation and diagnosis of skeletal dysplasia

The fetal skeleton is usually evaluated as part of a routine ultrasound around week 20 of the pregnancy.

If a skeletal dysplasia is suspected, the expectant mother will likely be referred to a facility that specializes in diagnosing, treating and caring for babies with congenital anomalies, such as the Center for Fetal Diagnosis and Treatment at The Children’s Hospital of Philadelphia.

At our Center, prenatal evaluation of skeletal dysplasias includes a detailed ultrasound of the fetal skeleton in the second or third trimester of gestation, and consideration of further genetic work-up. Low-dose fetal computed tomography (CT) is another imaging tool that aids in diagnosing skeletal dysplasias and may be considered depending on the findings in your pregancy.

Prenatal diagnosis of skeletal dysplasias remains challenging, especially when there is no family history of the disorders. This is because:

• Each skeletal dysplasia is rare. Some display the same physical characteristics, yet are molecularly different (caused by mutations in different genes). Conversely, some skeletal dysplasias display different physical characteristics, yet have similar genetic abnormalities.
• Some skeletal dysplasias are not apparent during the second trimester ultrasound. They only become evident in the third trimester, or even after birth, further complicating timely diagnosis.
• Ultrasound remains a limited imaging tool, even in the most experienced hands. Studies have indicated ultrasound has sensitivity in the range of 40 percent to 60 percent.

Attempting to pinpoint the specific genetic mutation, and therefore the particular skeletal dysplasia, can be critical to providing the most information about your child’s condition and potential prognosis. Therefore, our team will discuss the benefits and limitations of considering comprehensive genetic sequencing studies for the fetus through an amniocentesis. Alternatively, more limited genetic blood screening may be an option in some cases. Our team of genetic counselors and maternal-fetal medicine specialists are committed to helping each family navigate these options and decide what feels best for them moving forward. 

Long-term outlook for babies with skeletal dysplasias

The long-term outlook for babies with skeletal dysplasias varies greatly depending on the type of dysplasia, as well as associated abnormalities. About half of fetuses with skeletal dysplasia are stillborn or die within the first six weeks of life.

But not all children with dysplasias have severe medical problems. Many of these children can live relatively normal lives.

It is recommended that children born with or later diagnosed with a skeletal dysplasia be treated by a multidisciplinary team of experts, such as the one at The Children’s Hospital of Philadelphia.

By working with a coordinated team of geneticists, neonatologists, radiologists, orthopedists, pediatricians and specialists, your child will receive individualized care that addresses your child’s health, developmental and psychosocial needs.