Myhre syndrome is a rare genetic disorder that impacts connective tissue, the material that provides structure and flexibility to the body. This condition is characterized by a wide range of signs and symptoms affecting multiple body systems. The features of Myhre syndrome can vary in severity from person to person, and some may become more noticeable with age.
The Genetic Cause of Myhre Syndrome
Myhre syndrome is caused by a mutation in the SMAD4 gene, which provides instructions for a protein that transmits chemical signals from the cell surface to the nucleus. These signals control cell growth, proliferation, and specialization. The mutations are “gain-of-function,” meaning the SMAD4 gene becomes overactive. This overactivity disrupts the signaling pathways that regulate cell development.
The genetic change is a de novo mutation, meaning it occurs spontaneously and is not inherited from either parent. It happens by chance around conception and is not caused by any parental action. Because the SMAD4 gene affects many cellular processes, a single mutation leads to the widespread effects seen in this condition. Research suggests the mutation may alter how the SMAD4 protein binds to other proteins or make it abnormally stable, causing it to remain active longer than it should.
Physical and Developmental Characteristics
Individuals with Myhre syndrome have distinct physical traits. Many are born smaller than average and experience growth delays, resulting in short stature and a muscular build. Common facial features include:
- Narrow eye openings
- An underdeveloped upper jaw
- A short distance between the nose and upper lip
- A thin upper lip
- A small mouth
A protruding lower jaw, known as prognathism, may become more apparent with age.
Musculoskeletal and skin differences are common. Individuals have limited joint mobility, which can be stiff and may worsen over time. The bones of the arms and legs may be shortened, along with having short fingers and toes. The skin is often thick and firm, a change that begins in childhood on the palms, soles, elbows, and knees before spreading.
Developmental patterns vary. While some individuals may have mild to moderate intellectual disability, many have normal intelligence. Behavioral characteristics similar to those seen in autism spectrum disorder are sometimes observed. Early and consistent developmental monitoring is standard to identify any challenges.
Associated Health Complications
Myhre syndrome is associated with several internal health issues that often require specialized medical attention. Many of these complications are progressive, meaning they develop or worsen over time. The cardiovascular system is frequently affected, with structural heart problems sometimes present from birth. This includes the narrowing, or stenosis, of major blood vessels like the aorta and the pulmonary artery.
Progressive fibrosis, the buildup of scar-like tissue, can affect the skin and internal organs. This can cause high blood pressure (hypertension) and problems with the heart valves. The membrane surrounding the heart, the pericardium, can become inflamed and constricted. Restrictive lung disease, where the lungs cannot fully expand and make breathing difficult, can also occur.
Hearing loss is common, often starting in childhood and gradually becoming more pronounced. This impairment can impact learning and social development if not managed early. The upper airway, including the windpipe (trachea), can also narrow, leading to respiratory difficulties. Because these health issues can be serious, early identification and management is important.
Diagnosis and Symptom Management
Diagnosis begins with a clinical evaluation by a physician who recognizes the characteristic physical features. A suspected diagnosis is then confirmed through molecular genetic testing. This testing specifically looks for the gain-of-function mutation in the SMAD4 gene.
There is no cure for Myhre syndrome, so medical care focuses on managing symptoms and health complications to support the best possible quality of life. This requires a coordinated, multidisciplinary team of specialists. For example, a cardiologist monitors and treats heart and blood vessel issues, while a pulmonologist manages respiratory problems.
Physical therapists can help with joint stiffness and mobility, and audiologists address hearing loss with aids or other interventions. Due to the tendency for abnormal scarring, any planned surgeries must be approached with caution. The goal of this comprehensive management is to address health problems as they arise and support the best possible quality of life.