SNP Shot: Genomic Insights

Myhre syndrome is a rare genetic disorder affecting connective tissue, the material that provides strength and flexibility to various body structures. This condition presents with a wide array of signs and symptoms impacting multiple body systems, although not all individuals experience the same features. The severity of these characteristics can vary, and some become more pronounced as individuals age.

Common signs and symptoms include: short stature, skeletal abnormalities, limited joint movement, distinctive facial features, intellectual and behavioral challenges, hearing loss, a tendency to develop scar tissue (fibrosis) in the skin and internal organs, and heart and lung problems.

Reduced growth is typical in Myhre syndrome, starting before birth and continuing throughout childhood and adolescence. Affected individuals often have a low birth weight and remain shorter than the majority of their peers. Skeletal features include shortened arm and leg bones, unusually short fingers and toes (brachydactyly), and curved pinky fingers (clinodactyly). Other skeletal abnormalities may include thickening of the skull, flattened spinal bones (platyspondyly), broad ribs, and underdeveloped pelvic bones (hypoplastic iliac wings). Joint problems (arthropathy), such as stiffness and limited range of motion, are also frequently observed.

Distinctive facial characteristics include narrow eye openings (short palpebral fissures), deep-set eyes, a short distance between the nose and upper lip (short philtrum), a narrow mouth with a thin upper lip, an underdeveloped upper jaw, and a protruding lower jaw (prognathism). Some individuals are born with a cleft palate, cleft lip, or both. Vision problems are common, including eyes that don't align properly (strabismus), nearsightedness (myopia), farsightedness (hyperopia), irregular corneal curvature (astigmatism), clouding of the lens (cataracts), or, in rare cases, a condition affecting the back of the eye called pseudopapilledema.

Developmental delays are usually noticeable in children with Myhre syndrome by age 5, with speech and language delays being most prominent. Motor skill development, such as crawling and walking, may also be delayed, though these children typically learn to walk eventually. Intellectual disability, ranging from mild to moderate, is common; however, some individuals can hold jobs or pursue higher education.

Individuals with Myhre syndrome commonly exhibit characteristics similar to those seen in autism spectrum disorder, affecting communication and social interaction. The severity of these features varies and usually improves with time.

Hearing loss is common in Myhre syndrome, often starting in childhood and gradually worsening. Early detection is crucial, as hearing problems can contribute to learning and behavioral difficulties.

Fibrosis in Myhre syndrome can occur spontaneously or after surgery or trauma. Affected individuals typically develop stiff, thickened skin, usually beginning in childhood, most often on the palms, soles, elbows, and knees, later spreading to other areas. This thickening can lead to fewer facial wrinkles than expected for their age. Scars may become more noticeable or unusually thickened (keloids or hypertrophic scars).

Congenital heart defects are frequently observed in individuals with Myhre syndrome. Fibrosis in the heart and blood vessels (cardiovascular system) can lead to further complications like high blood pressure (hypertension) and narrowing (stenosis) of heart valves or blood vessels. Other cardiovascular issues may include inflammation and thickening of the pericardium (pericarditis) and, rarely, restrictive cardiomyopathy, where the heart muscle becomes stiff and cannot relax fully. These cardiovascular problems can be life-threatening.

Respiratory problems in Myhre syndrome include narrowing of the trachea (laryngotracheal stenosis) and the airways leading to the lungs (bronchi), difficulty fully inflating the lungs (restrictive pulmonary disease), or widespread lung damage (interstitial lung disease). These respiratory issues can be life-threatening.

Additional features of Myhre syndrome include gastrointestinal problems such as narrowing of the lower stomach (pyloric stenosis) or the upper small intestine (duodenal strictures) and severe constipation. Individuals may also have an increased risk of developing cancerous or noncancerous tumors, including cancer of the uterine lining (endometrial cancer).

Inheritance:

Myhre syndrome follows an autosomal dominant inheritance pattern, meaning only one copy of the altered SMAD4 gene is needed in each cell to cause the disorder. In the vast majority of cases, the condition arises from new mutations in the gene, occurring in individuals with no family history of the condition. Rarely, an affected person inherits the mutation from a parent who also has the condition.