What Are the Clinical Characteristics of the Most Common Skeletal Dysplasia?

Patient Presentation
A 4-year-old female came to clinic for her health maintenance examination. She had achrondroplasia and a history of otitis media but was otherwise well. She was doing well in preschool and there were no specific questions or concerns. The family history showed that her achondroplasia was from a new genetic mutation.

The pertinent physical exam showed a smiling female who was < 5% of length, but with 25% for weight and head circumference. She had shorter limbs with some lumbar lordosis with a relatively larger head and shortened neck. She had some otosclerosis bilaterally. Otherwise her examination was normal.

The diagnosis of a well preschooler with achondroplasia was made. The pediatrician remarked that he had re-reviewed some of the potential problems for patients with achrondroplasia before she came to the office. “You said she’s keeping up with the other kids and not having any problems moving as some patients have problems with their joints or low muscle tone, so I would continue to watch for this. Some patients also can have some lung problems too. Just watch out to see if she is having any problems breathing when she is playing or sleeping. If you think so, let me know right away,” he advised.

With more than 200 skeletal dysplasias and multiple variations even for one dysplasia, it can be difficult for the general practitioner to know a lot of specific information about all the skeletal dysplasias. Achondroplasia (ACP) is the most common skeletal dysplasia and specifically short-limbed dwarfism. The incidence is about 1 in 15-40,000 live births. ACP is autosomal dominant with about 80% arising from new mutations with a single nucleotide substitution in the fibroblast growth factor receptor 3 (FGFR3) gene on chromosome 4. This gene regulates the conversion of cartilage to bone, with the problem showing up after 22 weeks gestation. Therefore 2nd trimester fetal ultrasounds often will be normal.

Osteogenesis imperfecta (OI) is a connective tissue disorder (most commonly autosomal dominant) which may have skeletal dysplasia as well (some lethal variations). Classic OI has increased bone fragility and increased fractures. Fractures may be with no or minimal trauma and may occur in atypical locations. Severe forms can have fractures occurring in utero. Bony deformations and reduced bony growth can cause a variety of clinical problems including scoliosis and long-bone bowing. Problems which may overlap with ACP include hypermobility, muscle weakness, hearing loss, reduced pulmonary function and complications. Cardiovascular problems are also common with valvular dysfunction and aortic root dilatation. Dental dysplasia and abnormal coloration and bluish sclera may be seen as well.

Learning Point
Classic achondroplasia has the following clinical phenotype:

  • Shortened extremities particularly femur and humerus
  • Shortened fingers referred to sometimes as a trident hand
  • Facial features which have frontal bossing and midline facial hypoplasia
  • Shortened neck
  • Long trunk with lumbar lordosis
  • Hypotonia
  • Joint hypermobility
  • Normal intelligence but may have some gross and fine motor developmental delays
  • Redundant skin on extremities

As a result, patients have or may have:

  • Overall short stature – average adult height is around 132 cm in males, 124 cm in females. Most height loss occurs in first 2 years of life
  • Small foramen magnum and spinal canal cause compression of the spinal cord
    • Increased sudden infant death syndrome in this patient population may be because this is unrecognized
    • Hydrocephalus
  • Restrictive pulmonary disease
    • Obstructive sleep apnea
  • Gastroesophageal reflux disease
  • Otitis media with increased hearing and speech problems
  • Obesity
  • Mental health problems including body image
  • Increased mortality especially in first few years of life

There are several lethal dysplasias that present similarly to ACP. Homozygous ACP itself is lethal. Non-lethal dysplasias that are similar include chrondroplasia puncta, diastrophic dysplasia and spondyloepiphyseal dysplasia congenita. If the patient looks like they have ACP but has other congenital anomalies, other skeletal dysplasias should be considered as well. For patients with shortened limbs, other similar conditions include osteogensis imperfecta (see above), hypochondroplasia, hypophosphatasia, and thanatophoric dwarfism.

Accurate measurement of limbs to determine if the changes are proportionate or disproportionate are important in making the diagnosis of ACP along with changes on radiographs. Genetic testing can be helpful if the diagnosis is in question or for needed confirmation.

Treatment of ACP usually incudes education and support of the patient and families and monitoring and treatment for underlying problems. More recently growth hormone and C-natriuretic peptide analogs have been in clinical trials to try to increase overall height.

Questions for Further Discussion
1. What information resources do you use to review genetic diseases?
2. What disease- or condition- based patient support groups do you suggest families use?
3. What conditions have an increased risk of otitis media?
4. What is in the differential diagnosis of short stature? A review can be found here

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Dwarfism and Growth Disorders.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Daugherty A. Achondroplasia: Etiology, Clinical Presentation, and Management. Neonatal Network. 2017;36(6):337-342. doi:10.1891/0730-0832.36.6.337

Rossi V, Lee B, Marom R. Osteogenesis imperfecta – advancements in genetics and treatment. Curr Opin Pediatr. 2019;31(6):708-715. doi:10.1097/MOP.0000000000000813

Semler O, Rehberg M, Mehdiani N, Jackels M, Hoyer-Kuhn H. Current and Emerging Therapeutic Options for the Management of Rare Skeletal Diseases. Pediatr Drugs. 2019;21(2):95-106. doi:10.1007/s40272-019-00330-0

Hogler W, Ward LM. New developments in the management of achondroplasia. Wien Med Wochenschr. 2020;170(5):104-111. doi:10.1007/s10354-020-00741-6

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa