Marshall syndrome

Overview

Marshall syndrome is a rare genetic disorder primarily affecting connective tissues, resulting in characteristic facial features, eye abnormalities, hearing loss, and skeletal issues. It is considered part of a spectrum of conditions that includes Stickler syndrome, due to their overlapping features and shared genetic causes. Marshall syndrome is typically present at birth or develops early in life, and though it is a lifelong condition, its severity varies significantly among individuals.

First described by Dr. Don Marshall in 1958, the syndrome is caused by mutations affecting collagen production—a key structural protein in connective tissues. Because collagen is essential for the integrity of the eyes, ears, joints, and facial structures, Marshall syndrome presents with a constellation of symptoms that reflect this multi-system involvement.

Causes

Marshall syndrome is caused by mutations in the COL11A1 gene, which provides instructions for making one of the components of type XI collagen. Type XI collagen is critical for the normal development and function of connective tissues throughout the body.

The condition follows an autosomal dominant inheritance pattern, meaning only one copy of the mutated gene is sufficient to cause the disorder. In some cases, the mutation is inherited from an affected parent; in others, it arises spontaneously (de novo) without a family history.

Because of its close genetic and clinical relationship with Stickler syndrome, some researchers consider Marshall syndrome a variant form of Stickler syndrome type II or a related collagenopathy.

Symptoms

The clinical features of Marshall syndrome are diverse and vary in severity, but most individuals exhibit abnormalities in the eyes, ears, facial structure, and joints. Common symptoms include:

• Facial abnormalities:

  • Flat midface (midface hypoplasia)

  • Short nose with a flat nasal bridge

  • Prominent eyes and a small jaw (micrognathia)

  • Underdeveloped cheekbones

• Eye problems:

  • Severe myopia (nearsightedness) from early childhood

  • Cataracts, which may develop early in life

  • Glaucoma

  • Retinal detachment (a serious complication that can lead to blindness)

• Hearing loss:

  • Sensorineural hearing loss, typically bilateral

  • Often progressive, beginning in childhood or adolescence

• Joint and skeletal abnormalities:

  • Joint hypermobility or stiffness

  • Early-onset arthritis

  • Short stature in some cases

• Other features:

  • Cleft palate or submucous cleft palate (in some cases)

  • Dental anomalies such as crowded teeth or high-arched palate

The overall physical appearance, especially the characteristic facial structure, often becomes more recognizable with age. Intellectual development is typically normal.

Diagnosis

Diagnosing Marshall syndrome requires a comprehensive clinical evaluation, family history, and genetic testing. Diagnostic steps include:

• Physical examination: Recognition of the typical facial features, joint abnormalities, and growth patterns.

• Ophthalmologic evaluation: Assessment for myopia, cataracts, and retinal abnormalities.

• Audiological testing: Hearing tests to identify and monitor sensorineural hearing loss.

• Radiographic imaging: May reveal skeletal anomalies or joint abnormalities, especially in patients with joint pain or mobility issues.

• Genetic testing:

  • Sequencing of the COL11A1 gene to identify pathogenic variants

  • Helps differentiate Marshall syndrome from closely related disorders like Stickler syndrome

Because symptoms overlap with several other connective tissue disorders, genetic confirmation is essential for accurate diagnosis and family counseling.

Treatment

There is no cure for Marshall syndrome, so treatment focuses on managing symptoms and improving quality of life through a multidisciplinary approach. Management strategies include:

• Ophthalmologic care:

  • Corrective lenses for myopia

  • Cataract surgery if vision is significantly impaired

  • Monitoring for and managing retinal detachment or glaucoma

• Hearing support:

  • Use of hearing aids or cochlear implants for moderate to severe hearing loss

  • Regular audiologic follow-up

• Orthopedic and rheumatologic care:

  • Physical therapy to maintain joint mobility

  • Medications to manage arthritis or joint pain

• Surgical interventions:

  • Repair of cleft palate if present

  • Dental corrections for malocclusion or overcrowding

• Genetic counseling: For affected individuals and their families to discuss inheritance patterns and reproductive options.

Lifelong follow-up with specialists in ophthalmology, audiology, orthopedics, and genetics is often necessary to manage complications as they arise.

Prognosis

The prognosis for individuals with Marshall syndrome varies depending on the severity of the symptoms and the extent of organ involvement. While the condition is lifelong, many affected individuals lead productive lives with appropriate medical care and support.

Early detection and intervention—particularly for vision and hearing problems—can significantly improve outcomes. Most individuals have a normal life expectancy, although they may experience ongoing challenges related to vision, hearing, and joint mobility.

Advances in genetic research and improved access to supportive therapies continue to enhance the quality of life for individuals with Marshall syndrome. Increased awareness and early diagnosis remain key to optimal care.