More than 30 different signs and symptoms are variably associated with Marfan syndrome. The most prominent of these affect the skeletal, cardiovascular, and ocular systems, but all fibrous connective tissue throughout the body can be affected.

Most of the readily visible signs are associated with the skeletal system. Many individuals with Marfan syndrome grow to above-average height, and some have disproportionately long, slender limbs with thin, weak wrists and long fingers and toes. Besides affecting height and limb proportions, people with Marfan syndrome may have abnormal lateral curvature of the spine (scoliosis), thoracic lordosis, abnormal indentation (pectus excavatum) or protrusion (pectus carinatum) of the sternum, abnormal joint flexibility, a high-arched palate with crowded teeth and an overbite, flat feet, hammer toes, stooped shoulders, and unexplained stretch marks on the skin. It can also cause pain in the joints, bones and muscles. Some people with Marfan have speech disorders resulting from symptomatic high palates and small jaws. Early osteoarthritis may occur. Other signs include limited range of motion in the hips due to the femoral head protruding into abnormally deep hip sockets.

There is considerable variability in the phenotype of Loeys–Dietz syndrome, from mild features to severe systemic abnormalities. The primary manifestations of Loeys–Dietz syndrome are arterial tortuosity (winding course of blood vessels), widely spaced eyes (hypertelorism), wide or split uvula, and aneurysms at the aortic root. Other features may include cleft palate and a blue/gray appearance of the white of the eyes. Cardiac defects and club foot may be noted at birth.

There is overlap in the manifestations of Loeys–Dietz and Marfan syndromes, including increased risk of ascending aortic aneurysm and aortic dissection, abnormally long limbs and fingers, and dural ectasia (a gradual stretching and weakening of the dura mater that can cause abdominal and leg pain). Findings of hypertelorism (widely spaced eyes), bifrid or split uvula, and skin findings such as easy bruising or abnormal scars may distinguish Loys-Dietz from Marfan syndrome.

Findings of Loys-Dietz syndrome may include:

- Skeletal/spinal malformations: craniosynositosis, Scoliosis, spinal instability and spondylolisthesis, Kyphosis

- Sternal abnormalities: pectus excavatum, pectus carinatum

- Contractures of fingers and toes (camptodactyly)

- Long fingers and lax joints

- Weakened or missing eye muscles (strabismus)

- Club foot

- Premature fusion of the skull bones (craniosynostosis)

- Joint hypermobility

- Congenital heart problems including patent ductus arteriosus (connection between the aorta and the lung circulation) and atrial septal defect (connection between heart chambers)

- Translucency of the skin with velvety texture

- Abnormal junction of the brain and medulla (Arnold-Chiari malformation)

- Bicuspid aortic valves

- Criss-crossed pulmonary arteries

These symptoms were found in rare cases of Larsen syndrome.

- Cataracts

- Cleft palate

- Extra bones of wrist

- Malocclusion

- Microdontia and hypodontia

- Complete agenesis of anus

- uterus

- Bifid tongue

Symptoms are related to defects in connective tissue.

- Congenital anterior dislocation of the knees

- Dislocation of hips and shoulders

- Flattened facial appearance

- Prominent forehead

- Depressed nasal bridge

- Club foot

- Cervical kyphosis

MASS syndrome a medical disorder similar to Marfan syndrome.

MASS stands for: mitral valve prolapse, aortic root diameter at upper limits of normal for body size, stretch marks of the skin, and skeletal conditions similar to Marfan syndrome. MASS Phenotype is a connective tissue disorder that is similar to Marfan syndrome. It is caused by a similar mutation in the gene called fibrillin-1 that tells the body how to make an important protein found in connective tissue. This mutation is an autosomal dominant mutation in the FBN1 gene that codes for the extracellular matrix protein fibrillin-1; defects in the fibrillin-1 protein cause malfunctioning microfibrils that result in improper stretching of ligaments, blood vessels, and skin.

Someone with MASS phenotype has a 50 percent chance of passing the gene along to each child.

People with features of MASS Phenotype need to see a doctor who knows about connective tissue disorders for an accurate diagnosis; often this will be a medical geneticist. It is very important that people with MASS Phenotype get an early and correct diagnosis so they can get the right treatment. Treatment options for MASS phenotype are largely determined on a case-by-case basis and generally address the symptoms as opposed to the actual disorder; furthermore, due to the similarities between these two disorders, individuals with MASS phenotype follow the same treatment plans as those with Marfan syndrome.

MASS stands for the Mitral valve, myopia, Aorta, Skin and Skeletal features of the disorder. MASS Phenotype affects different people in different ways.

In MASS Phenotype:

Mitral valve prolapse may be present. This is when the flaps of one of the heart’s valves (the mitral valve, which regulates blood flow on the left side of the heart) are “floppy” and don’t close tightly. Aortic root diameter may be at the upper limits of normal for body size, but unlike Marfan syndrome there is not progression to aneurysm or predisposition to dissection. Skin may show stretch marks unrelated to weight gain or loss (striae). Skeletal features, including curvature of the spine (scoliosis), chest wall deformities, and joint hypermobility, may be present. People with MASS Phenotype do not have lens dislocation but have myopia, also known as nearsightedness.

MASS syndrome and Marfan syndrome are overlapping connective tissue disorders. Both can be caused by mutations in the gene encoding a protein called fibrillin. These conditions share many of the same signs and symptoms including long limbs and fingers, chest wall abnormalities (indented chest bone or protruding chest bone), flat feet, scoliosis, mitral valve prolapse, loose or hypextensible joints, highly arched roof of the mouth, and mild dilatation of the aortic root.

Individuals with MASS syndrome do not have progressive aortic enlargement or lens dislocation, while people with Marfan syndrome do. Skin involvement in MASS syndrome is typically limited to stretch marks (striae distensae). Also, the skeletal symptoms of MASS syndrome are generally mild.

Loeys–Dietz syndrome (LDS) is an autosomal dominant genetic connective tissue disorder. It has features similar to Marfan syndrome and Ehlers–Danlos syndrome. The disorder is marked by aneurysms in the aorta, often in children, and the aorta may also undergo sudden dissection in the weakened layers of the wall of aorta. Aneurysms and dissections also can occur in arteries other than the aorta. Because aneurysms in children tend to rupture early, children are at greater risk for dying if the syndrome is not identified. Surgery to repair aortic aneurysms is essential for treatment.

There are four types of the syndrome, labelled types I through IV, which are distinguished by their genetic cause. Type 1, Type 2, Type 3, and Type 4 are caused by mutations in "TGFBR1", "TGFBR2", "SMAD3", and "TGFB2" respectively. These four genes encoding transforming growth factors play a role in cell signaling that promotes growth and development of the body's tissues. Mutations of these genes cause production of proteins without function. Although the disorder has an autosomal pattern of inheritance, this disorder results from a new gene mutation in 75% of cases and occurs in people with no history of the disorder in their family.

Loeys-Dietz syndrome was identified and characterized by pediatric geneticists Bart Loeys and Harry Dietz at Johns Hopkins University in 2005.

The signs and symptoms of DOCK8 deficiency are similar to the autosomal dominant form, STAT3 deficiency. However, in DOCK8 deficiency, there is no skeletal or connective tissue involvement, and affected individuals do not have the characteristic facial features of those with autosomal dominant hyper-IgE syndrome. DOCK8 deficient children often have eczema, respiratory and skin staphylococcus infections.

Beyond these, many other recurrent infections have been observed, including recurrent fungal infections and recurrent viral infections (including molluscum contagiosum, herpes simplex, and herpes zoster), recurrent upper respiratory infection (including "Streptococcus pneumoniae", "Haemophilus influenzae", respiratory syncytial virus, and adenovirus), recurrent sinusitis, recurrent otitis media, mastoiditis, pneumonia, bronchitis with bronchiectasis, osteomyelitis, candidiasis, meningitis (caused by cryptococcus or H. influenzae), pericarditis, salmonella enteritis, and giardiasis. Other dermatologic problems include squamous-cell carcinoma/dysplasia (vulvar, anal, and facial). Immune problems are also common, including autoimmune hemolytic anemia, severe allergies (both food and environmental), asthma, and reactive airway disease. The nervous system may also be affected; observed conditions in DOCK8 deficient people include hemiplegia, ischemic stroke, subarachnoid hemorrhage, and facial paralysis. Vascular complications are common, including aortic aneurysm, cerebral aneurysm, vessel occlusion and underperfusion, and leukocytoclastic vasculitis.

Collagen, type II, alpha 1 (primary osteoarthritis, spondyloepiphyseal dysplasia, congenital), also known as COL2A1, is a human gene that provides instructions for the production of the pro-alpha1(II) chain of type II collagen.

"Maffucci syndrome" is a sporadic disease characterized by the presence of multiple enchondromas associated with multiple simple or cavernous soft tissue hemangiomas. Also lymphangiomas may be apparent.

Patients are normal at birth and the syndrome manifests during childhood and puberty. The enchondromas affect the extremities and their distribution is asymmetrical.

"Langer-Giedion syndrome" is a very rare genetic disorder caused by a deletion of chromosomal material. Diagnosis is usually made at birth or in early childhood.

The features associated with this condition include mild to moderate learning difficulties, short stature, unique facial features, small head and skeletal abnormalities including bony growths projecting from the surfaces of bones.

Children with DOCK8 deficiency do not tend to live long; sepsis is a common cause of death at a young age. CNS and vascular complications are other common causes of death.

Heberden's nodes are hard or bony swellings that can develop in the distal interphalangeal joints (DIP) (the joints closest to the end of the fingers and toes). They are a sign of osteoarthritis and are caused by formation of osteophytes (calcific spurs) of the articular (joint) cartilage in response to repeated trauma at the joint.

Heberden's nodes typically develop in middle age, beginning either with a chronic swelling of the affected joints or the sudden painful onset of redness, numbness, and loss of manual dexterity. This initial inflammation and pain eventually subsides, and the patient is left with a permanent bony outgrowth that often skews the fingertip sideways. Bouchard's nodes may also be present; these are similar bony growths in the proximal interphalangeal (PIP) joints (middle joints of the fingers), and are also associated with osteoarthritis.

Heberden's nodes are more common in women than in men, and there seems to be a genetic component involved in predisposition to the condition.

They are named after William Heberden (1710–1801).

Familial thoracic aortic aneurysm is an autosomal dominant disorder of large arteries.

There is an association between familial thoracic aortic aneurysm, Marfan syndrome and massive baclofen overdose as well as other hereditary connective tissue disorders.

Some common diseases affecting/involving the cartilage are listed below.

- Osteoarthritis: The cartilage covering bones (articular cartilage) is thinned, eventually completely worn out, resulting in a "bone against bone" joint, resulting in pain and reduced mobility. Osteoarthritis is very common, affects the joints exposed to high stress and is therefore considered the result of "wear and tear" rather than a true disease. It is treated by Arthroplasty, the replacement of the joint by a synthetic joint made of titanium and teflon. Chondroitin sulfate, a monomer of the polysaccharide portion of proteoglycan, has been shown to reduce the symptoms of osteoarthritis, possibly by increasing the synthesis of the extracellular matrix.

- Achondroplasia: Reduced proliferation of chondrocytes in the epiphyseal plate of long bones during infancy and childhood, resulting in dwarfism.

- Costochondritis: Inflammation of cartilage in the ribs, causing chest pain.

- Spinal disc herniation: Asymmetrical compression of an intervertebral disc ruptures the sac-like disc, causing a herniation of its soft content. The hernia compresses the adjacent nerves and causes back pain.

- Relapsing polychondritis: a destruction, probably autoimmune, of cartilage, especially of the nose and ears, causing disfiguration. Death occurs by suffocation as the larynx loses its rigidity and collapses.

- Cartilage tumors

Hypermobility generally results from one or more of the following:

- Abnormally shaped ends of one or more bones at a joint

- A Type 1 collagen or other connective tissue defect (as found in Ehlers-Danlos syndrome, Loeys-Dietz syndrome and Marfan syndrome) resulting in weakened ligaments/ligamentous laxity, muscles and tendons. This same defect also results in weakened bones, which may result in osteoporosis and fractures.

- Abnormal joint proprioception (an impaired ability to locate body parts in space and/or monitor an extended joint)

These abnormalities cause abnormal joint stress, meaning that the joints can wear out, leading to osteoarthritis.

The condition tends to run in families, suggesting a genetic basis for at least some forms of hypermobility. The term "double jointed" is often used to describe hypermobility; however, the name is a misnomer and should not be taken literally, as hypermobile joints are not doubled/extra in any sense.

Most people have hypermobility with no other symptoms. Approximately 5% of the healthy population have one or more hypermobile joints. However, people with "joint hypermobility syndrome" are subject to many difficulties. For example, their joints may be easily injured, be more prone to complete dislocation due to the weakly stabilized joint and they may develop problems from muscle fatigue (as muscles must work harder to compensate for weakness in the ligaments that support the joints). Hypermobility syndrome can lead to chronic pain or even disability in severe cases. Musical instrumentalists with hypermobile fingers may have difficulties when fingers collapse into the finger locking position. Or, conversely, they may display superior abilities due to their increased range of motion for fingering, such as in playing a violin or cello.

Hypermobility may be symptomatic of a serious medical condition, such as Stickler Syndrome, Ehlers-Danlos syndrome, Marfan syndrome, Loeys-Dietz syndrome, rheumatoid arthritis, osteogenesis imperfecta, lupus, polio, Down syndrome, morquio syndrome, cleidocranial dysostosis or myotonia congenita.

Hypermobility has been associated with chronic fatigue syndrome and fibromyalgia. Hypermobility causes physical trauma (in the form of joint dislocations, joint subluxations, joint instability, sprains, etc.). These conditions often, in turn, cause physical and/or emotional trauma and are possible triggers for conditions such as fibromyalgia.

Women with hypermobility may experience particular difficulties when pregnant. During pregnancy, the body releases certain hormones that alter ligament physiology, easing the stretching needed to accommodate fetal growth as well as the birthing process. The combination of hypermobility and pregnancy-related pelvic girdle during pregnancy can be debilitating. The pregnant woman with hypermobile joints will often be in significant pain as muscles and joints adapt to the pregnancy. Pain often inhibits such women from standing or walking during pregnancy. The pregnant patient may be forced to use a bedpan and/or a wheelchair during pregnancy and may experience permanent disability.

Symptoms of hypermobility include a dull but intense pain around the knee and ankle joints and the soles of the feet. The pain and discomfort affecting these body parts can be alleviated by using custom orthoses.

People with Joint Hypermobility Syndrome may develop other conditions caused by their unstable joints. These conditions include:

- Joint instability causing frequent sprains, tendinitis, or bursitis when doing activities that would not affect others

- Joint pain

- Early-onset osteoarthritis (as early as during teen years)

- Subluxations or dislocations, especially in the shoulder (severe limits to ability to push, pull, grasp, finger, reach, etc., is considered a disability by the US Social Security Administration)

- Knee pain

- Fatigue, even after short periods of exercise

- Back pain, prolapsed discs or spondylolisthesis

- Joints that make clicking noises (also a symptom of osteoarthritis)

- Susceptibility to whiplash

- Temporomandibular Joint Syndrome also known as TMJ

- Increased nerve compression disorders (such as carpal tunnel syndrome)

- The ability of finger locking

- Poor response to anaesthetic or pain medication

- "Growing pains" as described in children in late afternoon or night

In medicine, chondropathy refers to a disease of the cartilage. It is frequently divided into 5 grades, with 0-2 defined as normal, and 3-4 defined as diseased.

Symptoms are pain at the radial side of the wrist, spasms, tenderness, occasional burning sensation in the hand, and swelling over the thumb side of the wrist, and difficulty gripping with the affected side of the hand. The onset is often gradual. Pain is made worse by movement of the thumb and wrist, and may radiate to the thumb or the forearm.

Retroperitoneal fibrosis or Ormond's disease is a disease featuring the proliferation of fibrous tissue in the retroperitoneum, the compartment of the body containing the kidneys, aorta, renal tract, and various other structures. It may present with lower back pain, kidney failure, hypertension, deep vein thrombosis, and other obstructive symptoms. It is named after John Kelso Ormond, who rediscovered the condition in 1948.

De Quervain syndrome is diagnosed clinically, based on history and physical examination, though diagnostic imaging such as x-ray may be used to rule out fracture, arthritis, or other causes, based on the patient's history and presentation. Finkelstein's test is a physical exam maneuver used to diagnose de Quervain syndrome. To perform the test, the examiner grasps the thumb and sharply deviates the hand toward the ulnar side. If sharp pain occurs along the distal radius (top of forearm, about an inch below the wrist), de Quervain's syndrome is likely. While a positive Finkelstein's test is often considered pathognomonic for de Quervain syndrome, the maneuver can also cause pain in those with osteoarthritis at the base of the thumb.

Differential diagnoses include:

1. Osteoarthritis of the first carpo-metacarpal joint

2. Intersection syndrome—pain will be more towards the middle of the back of the forearm and about 2–3 inches below the wrist

3. Wartenberg's syndrome

Elbow dysplasia is a condition involving multiple developmental abnormalities of the elbow-joint in the dog, specifically the growth of cartilage or the structures surrounding it. These abnormalities, known as 'primary lesions', give rise to osteoarthritic processes. Elbow dysplasia is a common condition of certain breeds of dogs.

Most primary lesions are related to osteochondrosis, which is a disease of the joint cartilage and specifically Osteochondritis dissecans (OCD or OD), the separation of a flap of cartilage on the joint surface. Other common causes of elbow dysplasia included ununited anconeal process (UAP) and fragmented or ununited medial coronoid process (FCP or FMCP).

Osteochondritis dissecans is difficult to diagnose clinically as the animal may only exhibit an unusual gait. Consequently, OCD may be masked by, or misdiagnosed as, other skeletal and joint conditions such as hip dysplasia. The problem develops in puppyhood although often subclinically, and there may be pain or stiffness, discomfort on extension, or other compensating characteristics. Diagnosis generally depends on X-rays, arthroscopy, or MRI scans. While cases of OCD of the stifle go undetected and heal spontaneously, others are exhibited in acute lameness. Surgery is recommended once the animal has been deemed lame, before then non-surgical control is usually used.

The disorder is more common in older adults. The disease is often occult until crystal deposits are coincidentally detected and diagnosed by a pathologist in various orthopedic specimens. It may be asymptomatic, or it can be associated with osteoarthritis, or it can present as an acute or chronic inflammatory arthritis that causes pain in one or more joints. The white blood cell count is often raised.

The arthritis is usually polyarticular (i.e., it leads to an inflammation of several joints in the body), although it may begin as monoarticular (i.e., confined to just one joint). CPPD crystals tend to form within articular tissues. In theory, any joint may be affected, but statistics show that the knees are the most commonly affected joints, as well as wrists and hips.

In many instances, patients may also have signs of carpal tunnel syndrome. This condition can also be associated with Milwaukee shoulder syndrome.

This gene encodes the alpha-1 chain of type II collagen, a fibrillar collagen found in cartilage and the vitreous humor of the eye. Mutations in this gene are associated with achondrogenesis, chondrodysplasia, early onset familial osteoarthritis, SED congenita, Langer-Saldino achondrogenesis, Kniest dysplasia, Stickler syndrome type I, and spondyloepimetaphyseal dysplasia Strudwick type. In addition, defects in processing chondrocalcin, a calcium binding protein that is the C-propeptide of this collagen molecule, are also associated with chondrodysplasia. There are two transcripts identified for this gene.

Type II collagen, which adds structure and strength to connective tissues, is found primarily in cartilage, the jelly-like substance that fills the eyeball (the vitreous), the inner ear, and the center portion of the discs between the vertebrae in the spine (nucleus pulposus). Three pro-alpha1(II) chains twist together to form a triple-stranded, ropelike procollagen molecule. These procollagen molecules must be processed by enzymes in the cell. Once these molecules are processed, they leave the cell and arrange themselves into long, thin fibrils that cross-link to one another in the spaces around cells. The cross-linkages result in the formation of very strong mature type II collagen fibers.

The COL2A1 gene is located on the long (q) arm of chromosome 12 between positions 13.11 and 13.2, from base pair 46,653,017 to base pair 46,684,527.

The most common initial symptom of wrist osteoarthritis is joint pain. The pain is brought on by activity and increases when there is activity after resting. Other signs and symptoms, as with any joint affected by osteoarthritis, include:

- Morning stiffness, which usually lasts less than 30 minutes. This is also present in patients with rheumatoid arthritis, but in those patients this typically lasts for more than 45 minutes.

- Swelling of the wrist.

- Crepitus (crackling), which is felt when the hand is moved passively.

- Joint locking, where the joint is fixed in an extended position.

- Joint instability.

These symptoms can lead to loss of function and less daily activity.