Marshall syndrome is a

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

of the

connective tissue Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...

which can cause

hearing loss Hearing loss is a partial or total inability to Hearing, hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to Language ...

. The three most common areas to be affected are the eyes which are uncommonly large,

joint A joint or articulation (or articular surface) is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole.Saladin, Ken. Anatomy & Physiology. 7th ed. McGraw ...

s and the mouth and facial structures. Marshall syndrome and

Stickler syndrome Stickler syndrome (hereditary progressive arthro-ophthalmodystrophy) is a group of rare genetic disorders affecting connective tissue, specifically collagen. Stickler syndrome is a subtype of collagenopathy, types II and XI. Stickler syndrome i ...

closely resemble each other; in fact they are so similar, some say they are the same.

Presentation

Eyes

Myopia Near-sightedness, also known as myopia and short-sightedness, is an eye disease where light focuses in front of, instead of on, the retina. As a result, distant objects appear blurry while close objects appear normal. Other symptoms may include ...

is the most common eye problem in Marshall syndrome. Cataracts also occur more frequently and

detached retina Retinal detachment is a disorder of the eye in which the retina peels away from its underlying layer of support tissue. Initial detachment may be localized, but without rapid treatment the entire retina may detach, leading to vision loss and blin ...

less frequently than in Stickler syndrome.

also is the most common problem with the eyes in

. In the latter syndrome, extreme myopia may lead to severe eye problems such as detached retina more frequently than in Marshall syndrome.

Joints

The joint changes include hyperextensibility (double-jointedness) and

arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...

. Babies and young children with Stickler syndrome usually have very hyperextensible joints. As an affected child gets older, they may experience pain and stiffness from overuse of a joint.

Osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...

of the large joints often develops during the third or fourth decade. The joint changes in Marshall syndrome are of the same type but to a lesser degree. There also may be changes in the bones that show up on

X-ray An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 picometers to 10 nanometers, corresponding to frequencies in the range 30&nb ...

but generally are not a problem.

Orofacial Structure

The most severe problem associated with

Pierre Robin syndrome Pierre Robin sequence (; abbreviated PRS) is a congenital defect observed in humans which is characterized by facial abnormalities. The three main features are micrognathia (abnormally small mandible), which causes glossoptosis (downwardly displac ...

. This refers to a

cleft palate A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The te ...

resulting from a very small lower

jaw The jaw is any opposable articulated structure at the entrance of the mouth, typically used for grasping and manipulating food. The term ''jaws'' is also broadly applied to the whole of the structures constituting the vault of the mouth and serv ...

. During early

fetal A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal develo ...

life, the roof of the mouth is normally open and the sides of the

palate The palate () is the roof of the mouth in humans and other mammals. It separates the oral cavity from the nasal cavity. A similar structure is found in crocodilians, but in most other tetrapods, the oral and nasal cavities are not truly sepa ...

have to come together to close. If the jaw is too small, there is not enough room for the

tongue The tongue is a muscular organ (anatomy), organ in the mouth of a typical tetrapod. It manipulates food for mastication and swallowing as part of the digestive system, digestive process, and is the primary organ of taste. The tongue's upper surfa ...

which is then pushed up and gets in the way of the closing palate. Sometimes the chin is so small the baby has problems with eating and breathing if the tongue blocks the back of the

throat In vertebrate anatomy, the throat is the front part of the neck, internally positioned in front of the vertebrae. It contains the pharynx and larynx. An important section of it is the epiglottis, separating the esophagus from the trachea (windpipe ...

. Cleft palate is found less frequently in Marshall Syndrome than in Stickler syndrome but still more frequently than in the general population. The facial features of Marshall Syndrome include a flat midface, the appearance of large eyes, short upturned nose, and a round face. The facial features of Stickler syndrome are less prominent but include a rather long flat face, and depressed nasal bridge.

Hearing loss

The

associated with Stickler syndrome can be progressive and usually involves the high frequencies. Sensorineural hearing loss has been reported in as many as 100% and as low as 20% of affected individuals. A conductive loss due to

otitis Otitis is a general term for inflammation or infection, inner ear infection, middle ear infection of the ear, in both humans and other animals. When infection is present, it may be viral or bacterial. When inflammation is present due to fluid buil ...

can magnify an existing sensorineural loss and is a frequent problem for children with Stickler or Marshall Syndrome.

Genetics

Stickler syndrome and Marshall syndrome have an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

pattern of inheritance. However, there is a great deal of variation within and among families with regard to gene expression. Some may be more severely affected and others may be very mildly affected. Often these syndromes are not recognized in a family until a baby is born with

or some members have

detached retinas Retinal detachment is a disorder of the eye in which the retina peels away from its underlying layer of support tissue. Initial detachment may be localized, but without rapid treatment the entire retina may detach, leading to vision loss and blin ...

cataract A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble w ...

s at a young age. Both syndromes where correlated with mutations in the

COL11A1 Collagen alpha-1(XI) chain is a protein that in humans is encoded by the ''COL11A1'' gene. Function The COL11A1 gene encodes one of the two alpha chains of type XI collagen, a minor fibrillar collagen. Type XI collagen is a heterotrimer but t ...

gene.

Diagnosis

Diagnosis is made based on features as well as by the very early onset of serious eye and ear disease. Because Marshall syndrome is an autosomal dominant hereditary disease, physicians can also note the characteristic appearance of the

biological parent A parent is a caregiver of the offspring in their own species. In humans, a parent is the caretaker of a child (where "child" refers to offspring, not necessarily age). A ''biological parent'' is a person whose gamete resulted in a child, a male ...

of the child. A genetic test can be performed in Stickler syndrome diagnosis is made by doing a genetic test for the several collagen genes as well as other genes that are associated with Stickler as well as considering the presence and severity of Spondyloepiphyseal Dysplasia with association of reduced height and growth rate as well as other connective tissue features like skin hyperextensibility and poor wound healing. It is an area of active research, also the

genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

being expensive supports that the diagnosis is made depending on the features.

Treatment

There is no medical treatment for either syndrome but there are some recommendations that can help with prevention or early identification of some of the problems. Children with either syndrome should have their

hearing Hearing, or auditory perception, is the ability to perceive sounds In physics, sound is a vibration that propagates as an acoustic wave, through a transmission medium such as a gas, liquid or solid. In human physiology and psycholog ...

tested, and adults should be aware that the hearing loss may not develop until the adult years. Yearly visits to an

ophthalmologist Ophthalmology ( ) is a surgery, surgical subspecialty within medicine that deals with the diagnosis and treatment of eye disorders. An ophthalmologist is a physician who undergoes subspecialty training in medical and surgical eye care. Followin ...

or other

eye care professional An eye care professional (ECP) is an individual who provides a service related to the eyes or vision. It is any healthcare worker involved in eye care, from one with a small amount of post-secondary training to practitioners with a doctoral level ...

who has been informed of the diagnosis of Stickler or Marshall syndrome is important for all affected individuals. Children should have the opportunity to have myopia corrected as early as possible, and treatment for cataracts or detached retinas may be more effective with early identification. Support for the joints is especially important during sports, and some recommend that

contact sports Contact sports are sports that emphasize or require physical contact between players. Some sports, such as mixed martial arts, are scored on impacting an opponent, while others, including rugby football, gridiron football and Australian rules foot ...

should be avoided by those who have very loose joints.

References

External links

{{Scleroprotein disease Reactive neutrophilic cutaneous conditions Autosomal dominant disorders Rheumatology Rare genetic syndromes Collagen disease Syndromes affecting the eye Syndromes affecting hearing Syndromes with musculoskeletal abnormalities