Achondroplasia: A Genetic Disorder

What is Achondroplasia?

• A genetic disorder that affects the fibroblast growth factor receptor (FGFR3) protein, which regulates bone growth and maintenance.
• The most common type of short stature skeletal dysplasia or dwarfism.

Genetic Mutations

• Caused by specific pathogenic variants in FGFR3 on chromosome 4.
• An autosomal dominant disorder, where one copy of the mutated gene is sufficient to cause the disorder.
• 80% of cases result from new (de novo) mutations, which occur spontaneously in the sperm or egg of one of the parents or during early embryonic development.

Pathogenesis

• A specific mutation in the FGFR3 gene leads to an overactive receptor, inhibiting the proliferation and maturation of chondrocytes, which are responsible for cartilage formation.
• This results in shortened and improperly formed bones, particularly affecting the long bones in the arms and legs.

Signs and Symptoms

• Shortened bones (thigh, upper arm)
• Short hands and feet
• Large separation between third and fourth fingers
• Head is larger than normal
• Prominent forehead
• Midface hypoplasia
• Delayed development in infants (sitting, crawling, walking)
• Foramen magnum stenosis

Diagnosis

• Clinical Examination: Physical features such as large head size, prominent forehead, midface hypoplasia, short arms and legs, and short stature.
• Radiographic Examination: X-rays reveal characteristic skeletal abnormalities, such as shortening of the long bones, a narrowed foramen magnum, and a small vertebral canal.
• Genetic Testing: FGFR3 mutation testing can identify the mutations.

Treatment and Management

• No specific treatment for achondroplasia, but managing symptoms and monitoring height, weight, and head circumference during infancy.
• No cure for achondroplasia, but most people with the condition can live full and healthy lives.

Oral and Dental Manifestations

• Midface hypoplasia: underdevelopment of the midface, resulting in a concave facial profile and a prominent lower jaw.
• Dental crowding: reduced space in the upper jaw, leading to crowding of teeth.
• Delayed dental development: slower eruption of primary and permanent teeth.
• Malocclusion: misalignment of teeth, particularly Class III malocclusion (underbite).
• Narrow dental arches: constricted upper and lower dental arches.
• High-arched palate: elevated roof of the mouth, affecting speech and feeding.
• Bite issues: problems with how the teeth come together, affecting chewing and speech.
• Increased risk of dental caries and periodontal disease: higher risk of cavities and gum disease due to crowding and difficulty in maintaining oral hygiene.
• Jaw growth and function problems: abnormal jaw growth patterns, leading to chewing difficulties and temporomandibular joint (TMJ) disorders.
• Airway obstruction: narrowing of the airway due to facial structure anomalies, leading to obstructive sleep apnea.

Management Strategies

• Interdisciplinary approach: collaboration between pediatric dentists, orthodontists, maxillofacial surgeons, and other healthcare providers.
• Early orthodontic intervention: early assessment by an orthodontist to plan for space maintenance, expansion of dental arches, and correction of malocclusion.
• Maxillary expansion: rapid maxillary expansion may be indicated to address the narrow maxilla and improve dental arch space.
• Orthognathic surgery: in severe cases of malocclusion and maxillary hypoplasia, orthognathic surgery may be necessary to correct jaw alignment.
• Regular dental check-ups: frequent dental visits to monitor dental development, manage caries risk, and address any emerging issues promptly.