Marshall syndrome is a rare, inherited genetic condition characterized by distinctive features affecting various parts of the body. This disorder primarily impacts connective tissue, the material that provides structure and support to organs and other tissues throughout the body. As a result, Marshall syndrome is categorized as a collagenopathy, meaning it involves abnormalities in collagen, a major protein component of connective tissue.
Physical Characteristics and Symptoms
Individuals with Marshall syndrome often present with a combination of unique physical characteristics, which are frequently noticeable during childhood. These features can affect the face, eyes, ears, and skeletal system.
Craniofacial Features
A distinctive flat nasal bridge and upturned nostrils are common facial characteristics. Many individuals also exhibit wide-set eyes, a condition known as hypertelorism, along with a prominent forehead. A small chin, or micrognathia, can also be present.
Ocular (Eye) Problems
Eye issues are common. High myopia (severe nearsightedness) is frequently observed and can lead to blurred distance vision. Individuals also have an increased susceptibility to developing cataracts (clouding of the eye’s lens) and glaucoma (a condition that damages the optic nerve). There is also a heightened risk of retinal detachment, where the retina pulls away from its supporting tissue.
Auditory (Hearing) Issues
Hearing impairment is another common manifestation of the syndrome. This often involves sensorineural hearing loss, which originates from damage to the inner ear or the nerve pathways from the inner ear to the brain. This type of hearing loss can be progressive, meaning it may worsen over time.
Skeletal and Joint Abnormalities
Connective tissue involvement extends to the skeletal system, leading to joint abnormalities. Joint hypermobility (unusually flexible joints) is common. This can sometimes contribute to early-onset arthritis, causing joint pain and stiffness. Some individuals may also experience short stature, and a cleft palate (an opening in the roof of the mouth) can also occur.
Genetic Origins
Marshall syndrome is caused by an alteration in the COL11A1 gene. This gene contains instructions for producing a component of type XI collagen. Type XI collagen is a complex protein that plays a role in the normal development and function of various connective tissues throughout the body, including those found in the eyes, ears, and joints.
When a mutation occurs in the COL11A1 gene, it disrupts the formation of type XI collagen, leading to the symptoms observed in Marshall syndrome. The inheritance pattern is autosomal dominant. This means a person only needs to inherit one copy of the mutated COL11A1 gene from one parent to develop the condition.
The Diagnostic Process
Identifying Marshall syndrome begins with a clinical evaluation by a healthcare professional. This initial assessment involves a review of the patient’s medical history and family history, looking for patterns of similar symptoms within relatives. The doctor will also recognize characteristic physical signs associated with the syndrome.
Following the initial clinical assessment, specialized examinations are performed to confirm the diagnosis and evaluate the extent of the condition. An eye examination by an ophthalmologist is standard to assess for vision problems, cataracts, and glaucoma. Similarly, an audiologist will conduct hearing tests to determine the presence and severity of hearing loss.
A definitive diagnosis of Marshall syndrome is established through molecular genetic testing. This testing method involves analyzing a sample of the patient’s DNA, obtained from a blood sample. The genetic test looks for a mutation within the COL11A1 gene, which confirms the diagnosis.
Symptom Management and Care
Since there is no cure for Marshall syndrome, management focuses on addressing and alleviating symptoms. This approach requires an effort from a multidisciplinary team of healthcare specialists. This team may include ophthalmologists, audiologists, orthopedists, and geneticists.
For vision-related issues, corrective lenses are prescribed to manage nearsightedness and improve vision. Regular monitoring for glaucoma is performed, and if necessary, medications or surgical procedures can control eye pressure. Cataracts can be surgically removed when they impair vision, and retinal detachment requires surgical repair to prevent permanent vision loss.
Hearing loss is managed with interventions to improve communication. Hearing aids are commonly used to amplify sounds and improve hearing. In cases of severe hearing loss, cochlear implants, which are electronic devices that provide a sense of sound, may be considered.
Physical therapy plays a role in managing joint pain and discomfort. This therapy helps maintain joint mobility, strengthen surrounding muscles, and prevent further injury. If a cleft palate is present, surgical repair is performed to close the opening and facilitate feeding and speech development. Regular follow-up appointments with the specialized medical team monitor the progression of symptoms and adjust management strategies as needed.
Relationship to Stickler Syndrome
Marshall syndrome exhibits clinical overlap with a form of Stickler syndrome, known as Stickler syndrome type II. Both conditions are linked to mutations in the COL11A1 gene, which highlights their shared genetic basis. The similar genetic origin leads to many shared physical characteristics, particularly those affecting the eyes, ears, and joints.
Due to this overlap in genetic cause and clinical presentation, there is discussion within the medical community. Some experts consider Marshall syndrome and Stickler syndrome type II to be distinct disorders with similar features, while others view them as different expressions or variations of the same underlying condition. This connection highlights the complex nature of genetic disorders affecting connective tissue and the challenges in their classification.