Clinically and radiologically the disease is characterized by severe shortening of long bones (limb's both proximal and median segments are affected), aplasia or severe hypoplasia of ulna and fibula, thickened and curved radius and tibia. These anomalies can cause deformities of the hands and feet. Hypoplasia of the mandible can also be present.

It's part of the mesomelic and rhizomelic skeletal dysplasias, primary bone diseases in which the short stature is due to a lack of complete bone development of the limb's long bones.

It's strictly related to another disease, the Léri–Weill dyschondrosteosis, of which it seems to be the homozygothic variant, clinically more severe (it differs from this disorder for the absence, in some cases, of the Madelung deformity too).

Léri–Weill dyschondrosteosis or LWD is a rare pseudoautosomal dominant genetic disorder which results in dwarfism with short forearms and legs (mesomelic dwarfism) and a bayonet-like deformity of the forearms (Madelung's deformity).

Mesomelia refers to conditions in which the middle parts of limbs are disproportionately short. When applied to skeletal dysplasias, mesomelic dwarfism describes generalised shortening of the forearms and lower legs. This is in contrast to rhizomelic dwarfism in which the upper portions of limbs are short such as in achondroplasia.

Forms of mesomelic dwarfism currently described include:

- Langer mesomelic dysplasia

- Ellis–van Creveld syndrome

- Robinow syndrome

- Léri–Weill dyschondrosteosis

The clinical features of this condition include

- Flattened facial features

- Flexion contractures of the interphalangeal joints of hand and foot.

- Limited motion of multiple joints

- Short broad metacarpals, metatarsals and phalanges

Thickening of the skin may occur in a fashion similar to that occurs in scleroderma. The thumbs may be angled in a lateral direction (valgus deformity). The knees may be angled backwards (genu recurvatum). Abnormalities of the upper spinal cord may also occur.

It is a congenital subluxation or dislocation of the ulna's distal end, due to malformation of the bones. Sometimes, minor abnormalities of other bone structures, often caused by disease or injury, such as a fracture of the distal end of the radius with upward displacement of the distal fragment. The deformity varies in degree from a slight protrusion of the lower end of the ulna, to complete dislocation of the inferior radio-ulnar joint with marked radial deviation of the hand. Severe deformities are associated with congenital absence or hypoplasia of the radius.

The male:female rate of this disorder is 1:4. The incidence is unknown, and there is no described racial predominance. Even though Madelung's Deformity is considered a congenital disorder, symptoms sometimes aren't seen until adulthood. In most cases, symptoms find their onset during midchildhood. At this age, the relatively slower growth of the ulnar and palmar part of the radius, leads to an increasingly progressive deformity. Pain and deformity are the main symptoms patients present with. Typical clinical presentation consists of a short forearm, anterior-ulnar bow of the radius and a forward subluxation of the hand on the forearm. As mentioned before, the severity of the disorder varies greatly, which also leads to a spectrum of presentation.

It is caused by mutations in the SHOX gene found in the pseudoautosomal region PAR1 of the X and Y chromosomes, at band Xp22.33 or Yp11.32.

SHOX gene deletions have been identified as the major cause of Leri–Weill syndrome.

Leri–Weill dyschondrosteosis is characterized by mesomelic short stature, with bowing of the radius more so than the ulna in the forearms and bowing of the tibia while sparing the fibula.

Madelung's deformity is usually characterized by malformed wrists and wrist bones and is often associated with Léri-Weill dyschondrosteosis. It can be bilateral (in both wrists) or just in the one wrist.

It has only been recognized within the past hundred years.

Leri's pleonosteosis is a rare rheumatic condition. It was first described by the French physician Leri in 1921.

For a person with arthritis mutilans in the hands, the fingers become shortened by arthritis, and the shortening may become severe enough that the hand looks paw-like, with the first deformity occurring at the interphalangeal and metacarpophalangeal joints. The excess skin from the shortening of the phalanx bones becomes folded transversely, as if retracted into one another like opera glasses, hence the description "la main en lorgnette". As the condition worsens, luxation, phalangeal and metacarpal bone absorption, and skeletal architecture loss in the fingers occurs.

Microspherophakia is a rare congenital autosomal recessive condition where the lens of the eye is smaller than normal and spherically shaped. This condition may be associated with a number of disorders including Peter's anomaly, Marfan syndrome, and Weill–Marchesani syndrome. The spherical shape is caused by an underdeveloped zonule of Zinn, which doesn't exert enough force on the lens to make it form the usual oval shape. It is a result of a homozygous mutation to the LTBP2 gene.

Enthesitis can assist in differentiating arthritis mutilans' parent condition psoriatic arthritis from rheumatoid arthritis and osteoarthritis, with evidence in plain radiographs (x-rays) and MRI as periostitis, new bone formation, and bone erosions. Dactylitis, spondylitis and sacroiliitis are common with the parent condition psoriatic arthritis, but are not in rheumatoid arthritis. MRI bone edema scores are high in arthritis mutilans and correlate with radiographic measures of joint damage, although they may not correlate with disease activity. A source of significant pain, bone marrow edema (or lesions, using newer terminology), can be detected on MRI or with ultrasonography by signals of excessive water in bone marrow. Specifically, bone marrow edema can be detected within bone on T1-weighted images as poorly defined areas of low signal, with a high signal on T2-weighted fat-suppressed images. Comparatively, with arthritis mutilans in "rheumatoid arthritis", bone marrow edema often involves the bone layer, while the condition as a subtype of "psoriatic arthritis" includes a greater extent of marrow edema, expanding to diaphysis.

Weill–Marchesani syndrome is a rare genetic disorder characterized by short stature; an unusually short, broad head (brachycephaly) and other facial abnormalities; hand defects, including unusually short fingers (brachydactyly); and distinctive eye (ocular) abnormalities. It was named after ophthalmologists Georges Weill (1866-1952) and Oswald Marchesani (1900-1952) who first described it in 1932 and 1939, respectively.

The eye manifestations typically include unusually small, round lenses of the eyes (spherophakia), which may be prone to dislocating (ectopia lentis), as well as other ocular defects. Due to such abnormalities, affected individuals may have varying degrees of visual impairment, ranging from nearsightedness myopia to blindness. Researchers suggest that Weill–Marchesani syndrome may have autosomal recessive or autosomal dominant inheritance.

Diagnosis is made when several characteristic clinical signs are observed. There is no single test to confirm the presence of Weill–Marchesani syndrome. Exploring family history or examining other family members may prove helpful in confirming this diagnosis.

Beta thalassemias (β thalassemias) are a group of inherited blood disorders. They are forms of thalassemia caused by reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to clinically asymptomatic individuals. Global annual incidence is estimated at one in 100,000. Beta thalassemias are caused by mutations in the "HBB" gene on chromosome 11, inherited in an autosomal recessive fashion. The severity of the disease depends on the nature of the mutation.

HBB blockage over time leads to decreased beta-chain synthesis. The body's inability to construct new beta-chains leads to the underproduction of HbA. Reductions in HbA available overall to fill the red blood cells in turn leads to microcytic anemia. Microcytic anemia ultimately develops in respect to inadequate HBB protein for sufficient red blood cell functioning. Due to this factor, the patient may require blood transfusions to make up for the blockage in the beta-chains. Repeated blood transfusions can lead to build-up of iron overload, ultimately resulting in iron toxicity. This iron toxicity can cause various problems, including myocardial siderosis and heart failure leading to the patient’s death.

Three main forms have been described: thalassemia major, thalassemia intermedia, and thalassemia minor. All people with thalassemia are susceptible to health complications that involve the spleen (which is often enlarged and frequently removed) and gallstones. These complications are mostly found in thalassemia major and intermedia patients. Individuals with beta thalassemia major usually present within the first two years of life with severe anemia, poor growth, and skeletal abnormalities during infancy. Untreated thalassemia major eventually leads to death, usually by heart failure; therefore, birth screening is very important.

Excess iron causes serious complications within the liver, heart, and endocrine glands. Severe symptoms include liver cirrhosis, liver fibrosis, and in extreme cases, liver cancer. Heart failure, growth impairment, diabetes and osteoporosis are life-threatening contributors brought upon by TM. The main cardiac abnormalities seen to have resulted from thalassemia and iron overload include left ventricular systolic and diastolic dysfunction, pulmonary hypertension, valveulopathies, arrhythmias, and pericarditis. Increased gastrointestinal iron absorption is seen in all grades of beta thalassemia and increased red blood cell destruction by the spleen due to ineffective erythropoiesis further releases additional iron into the bloodstream.

Early signs and symptoms of the disorder usually appear around ages 2–10, with gradual onset of vision problems, or seizures. Early signs may be subtle personality and behavior changes, slow learning or regression, repetitive speech or echolalia, clumsiness, or stumbling. Slowing head growth in the infantile form, poor circulation in lower extremities (legs and feet), decreased body fat and muscle mass, curvature of the spine, hyperventilation and/or breath-holding spells, teeth grinding, and constipation may occur.

Over time, affected children suffer mental impairment, worsening seizures, and progressive loss of sight, speech, and motor skills. Batten disease is a terminal disease; life expectancy varies depending on the type or variation.

Females with juvenile Batten disease show first symptoms a year later than males, but on average die a year sooner.

Neuronal ceroid lipofuscinosis (NCL) is the general name for a family of at least eight genetically separate neurodegenerative disorders that result from excessive accumulation of lipopigments (lipofuscin) in the body's tissues. These lipopigments are made up of fats and proteins. Their name comes from the word stem "lipo-", which is a variation on "lipid" or "fat", and from the term "pigment", used because the substances take on a greenish-yellow color when viewed under an ultraviolet light microscope. These lipofuscin materials build up in neuronal cells and many organs, including the liver, spleen, myocardium, and kidneys.

Batten disease is a fatal disease of the nervous system that typically begins in childhood. Onset of symptoms is usually between 5 and 10 years of age. Often it is autosomal recessive. It is the most common form of a group of disorders called the neuronal ceroid lipofuscinoses (NCLs).

Although Batten disease is usually regarded as the juvenile form of NCL (or "type 3"), some physicians use the term Batten disease to describe all forms of NCL. Historically, the NCLs were classified by age of disease onset as infantile NCL (INCL), late infantile NCL (LINCL), juvenile NCL (JNCL) or adult NCL (ANCL). At least 20 genes have been identified in association with Batten disease, but juvenile NCL, the most prevalent form of Batten disease, has been linked to mutations in the "CLN3" gene.

It was first described in 1903.

The classic characterization of the group of neurodegenerative, lysosomal storage disorders called the neuronal ceroid lipofuscinoses (NCLs) is through the progressive, permanent loss of motor and psychological ability with a severe intracellular accumulation of lipofuscins, with the United States and northern European populations having slightly higher frequency with an occurrence of 1 in 10,000. There are four classic diagnoses that have received the most attention from researchers and the medical field, differentiated from one another by age of symptomatic onset, duration, early-onset manifestations such as blindness or seizures, and the forms which lipofuscin accumulation takes.

In the early infantile variant of NCL (also called INCL or Santavuori-Haltia), probands appear normal at birth, but early visual loss leading to complete retinal blindness by the age of 2 years is the first indicator of the disease; by 3 years of age a vegetative state is reached and by 4 years isoelectric encephalograms confirm brain death. Late infantile variant usually manifests between 2 and 4 years of age with seizures and deterioration of vision. The maximum age before death for late infantile variant is 10–12 years. Juvenile NCL (JNCL, Batten Disease, or Spielmeyer-Vogt), with a prevalence of 1 in 100,000, usually arises between 4 and 10 years of age; the first symptoms include considerable vision loss due to retinal dystrophy, with seizures, psychological degeneration, and eventual death in the mid- to late-20s or 30s ensuing. Adult variant NCL (ANCL or Kuf’s Disease) is less understood and generally manifests milder symptoms; however, while symptoms typically appear around 30 years of age, death usually occurs ten years later.

All the mutations that have been associated with this disease have been linked to genes involved with the neural synapses metabolism – most commonly with the reuse of vesicle proteins.

Lens subluxation is also seen in dogs and is characterized by a partial displacement of the lens. It can be recognized by trembling of the iris (iridodonesis) or lens (phacodonesis) and the presence of an aphakic crescent (an area of the pupil where the lens is absent). Other signs of lens subluxation include mild conjunctival redness, vitreous humour degeneration, prolapse of the vitreous into the anterior chamber, and an increase or decrease of anterior chamber depth. Removal of the lens before it completely luxates into the anterior chamber may prevent secondary glaucoma. A nonsurgical alternative involves the use of a miotic to constrict the pupil and prevent the lens from luxating into the anterior chamber.

Ectopia lentis is a displacement or malposition of the eye's crystalline lens from its normal location. A partial dislocation of a lens is termed "lens subluxation" or "subluxated lens"; a complete dislocation of a lens is termed "lens luxation" or "luxated lens".

It may affect any part of the brain or even the spinal cord, optic nerve and compact white matter. Clinical manifestations are indefinite, and include headache, seizures, visual disturbances, corticospinal tract deficits, lethargy, and dementia. A case of gliomatosis cerebri presenting as rapidly progressive dementia and Parkinson's disease like symptoms has been described in an 82-year-old woman.

Before the advent of MRI, diagnosis was generally not established until autopsy. Even with MRI, however, diagnosis is difficult. Typically, gliomatosis cerebri appears as a diffuse, poorly circumscribed, infiltrating non-enhancing lesion that is hyperintense on T2-weighted images and expands the cerebral white matter. It is difficult to distinguish from highly infiltrative anaplastic astrocytoma or GBM.