Achondroplasia PDF

Achondroplasia Doctor : Duaa Quedan Done by : Hala Atallah Malak Masalha Salma Almomani Shahed khayyat Jawaher sukhtian Dania al abadi Farah  What is Achondroplasia ? Achondroplasia is a genetic disorder that impacts a protein in the body known as the fibroblast...

Achondroplasia Doctor : Duaa Quedan Done by : Hala Atallah Malak Masalha Salma Almomani Shahed khayyat Jawaher sukhtian Dania al abadi Farah  What is Achondroplasia ? Achondroplasia is a genetic disorder that impacts a protein in the body known as the fibroblast growth factor receptor (FGFR3). The FGFR3 gene is responsible for encoding a protein that plays a crucial role in the regulation of bone growth and maintenance, as well as the development of brain tissue. This protein acts as a receptor that transmits signals to cells to regulate their growth and division.  Genetic mutations The most common type of short stature skeletal dysplasia or dwarfism, is an autosomal dominant disorder caused by specific pathogenic variants in FGFR3 on chromosome 4. One copy of the mutated gene is sufficient to cause the disorder. If one parent has achondroplasia, there is a 50% chance that their child will inherit the condition. In cases where both parents have achondroplasia, the risks increase, with a 50% chance of the child having achondroplasia, a 25% chance of inheriting two copies of the mutation (which is usually fatal shortly after birth), and a 25% chance of not inheriting the mutation. 80% of cases, achondroplasia results from new (de novo) mutations. These are spontaneous mutations that occur in the sperm or egg of one of the parents, or during early embryonic development. Parents of children with de novo mutations typically do not have the condition themselves and are not carriers of the mutated gene.  Genetic mutations In individuals with achondroplasia, a specific mutation in the FGFR3 gene leads to an overactive receptor. This hyperactivity of the FGFR3 protein inhibits the proliferation and maturation of chondrocytes, which are the cells responsible for cartilage formation. Since cartilage is a precursor to bone during early development, this inhibition results in shortened and improperly formed bones, particularly affecting the long bones in the arms and legs.  Genetic mutations Pathogenesis FGFR3 is a transmembrane tyrosine kinase receptor that binds fibroblast growth factors. Binding of fibroblast growth factors to the extracellular domain of FGFR3 activates the intracellular tyrosine kinase domain of the receptor and initiates a signaling cascade. In endochondral bone, FGFR3 activation inhibits proliferation of chondrocytes within the growth plate and thus helps coordinate the growth and differentiation of chondrocytes with the growth and differentiation of bone progenitor cells. Signs and Symptoms of Achondroplasia Bones are shortened (thigh, upper arm). Short hands and feet. Large separation between third and fourth fingers. Head is larger than normal. Prominent forehead. Midface hypoplasia, collapsed midface, deficient maxilla, and an elongated lower face Flat nasal bone. Delayed development in infants (sitting, crawling, walking). Foramen magnum stenosis.  Diagnosis I. Clinical Examination: Physical Features: Individuals with achondroplasia typically have distinct physical features such as a large head size (macrocephaly), a prominent forehead, midface hypoplasia (underdeveloped midfacial region), short arms and legs, and short stature. Growth Patterns: Monitoring growth patterns and comparing them to standard growth charts for achondroplasia can help identify the disorder. II. Radiographic Examination: X-rays: X-rays can reveal characteristic skeletal abnormalities such as shortening of the long bones, a narrowed foramen magnum (the opening at the base of the skull), and a small vertebral canal. These imaging techniques can provide detailed views of the bones and brain structure, helping to identify features typical of achondroplasia.  Diagnosis III. Genetic Testing: FGFR3 Mutation Testing: Achondroplasia is caused by mutations in the FGFR3 gene. Genetic testing can identify these mutations. This test can be performed using a blood sample or a sample from a prenatal procedure like amniocentesis or chorionic villus sampling (CVS). IV. some ways to detect achondroplasia before pregnancy: Ultrasound: Prenatal ultrasounds can sometimes detect features suggestive of achondroplasia, such as shortening of the long bones, during the second or third trimester of pregnancy. Non-Invasive Prenatal Testing (NIPT): This blood test can analyze fetal DNA circulating in the mother's blood and detect FGFR3 mutations associated with achondroplasia. Treatment There is no specific treatment for achondroplasia other than managing symptoms. Monitoring height, weight, and head circumference is recommended during infancy to track growth progress. There is NO cure for achondroplasia, but most people diagnosed with the condition can live full and healthy lives. Oral and Dental Manifestations 1. Midface Hypoplasia: Description: Underdevelopment of the midface. Implications: Results in a concave facial profile and makes the lower jaw appear more prominent. 2. Dental Crowding: Description: Reduced space in the upper jaw. Implications: Leads to crowding of teeth, often requiring orthodontic treatment. 3. Delayed Dental Development: Description: Slower eruption of primary and permanent teeth. Implications: Affects timing for orthodontic and other dental interventions. 4. Malocclusion: Description: Misalignment of teeth, particularly Class III malocclusion (underbite). Implications: Due to midface hypoplasia and normal mandibular growth. 5. Narrow Dental Arches: Description: Constricted upper and lower dental arches. Implications: Further contributes to crowding and misalignment of teeth. Oral and Dental Manifestations 6. High-Arched Palate: Description: Elevated roof of the mouth. Implications: Can affect speech and feeding. 7. Bite Issues: Description: Problems with how the teeth come together, such as open bites or crossbites. Implications: Affects chewing and speech. 8. Increased Risk of Dental Caries and Periodontal Disease: Description: Higher risk of cavities and gum disease. Implications: Due to crowding and difficulty in maintaining oral hygiene. 9. Jaw Growth and Function Problems: Description: Abnormal jaw growth patterns. Implications: Leads to chewing difficulties and temporomandibular joint (TMJ) disorders. 10. Airway Obstruction: Description: Narrowing of the airway due to facial structure anomalies. Implications: Can lead to obstructive sleep apnea, associated with dental crowding and malocclusion. Management strategies 1. Interdisciplinary Approach: Collaboration between pediatric dentists, orthodontists, maxillofacial surgeons, and other healthcare providers is crucial for comprehensive care. 2. Early Orthodontic Intervention: Early assessment by an orthodontist can help in planning for space maintenance, expansion of dental arches, and correction of malocclusion. 3. Maxillary Expansion: Rapid maxillary expansion may be indicated to address the narrow maxilla and improve dental arch space. 4. Orthognathic Surgery: In severe cases of malocclusion and maxillary hypoplasia, orthognathic surgery may be necessary to correct jaw alignment. Management strategies 5. Regular Dental Check-Ups: Frequent dental visits to monitor dental development, manage caries risk, and address any emerging issues promptly. 6. Preventive Care: Emphasis on preventive dental care, including fluoride treatments, dental sealants, and oral hygiene education to prevent caries and periodontal disease. 7. Management of Sleep Apnea: Due to midface hypoplasia, patients may be at risk for obstructive sleep apnea. Dental appliances or referral to a sleep specialist may be necessary. 8. Custom Dental Appliances: Custom-made appliances for space maintenance or correction of malocclusion should be considered References Achondroplasia: Symptoms, Treatment, Causes & Diagnosis (clevelandclinic.org) Achondroplasia | Johns Hopkins Medicine Thompson & Thompson Genetics in Medicine, 8e (Jun 4, 2015)_(1437706967)_(Elsevier).pdf https://youtu.be/BenGGuub6ZQ achondroplasia-information-booklet_sept-22.pdf (nhsggc.org.uk)