PDP has a number of visible symptoms. Most important clinical features are: pachydermia (thickening and wrinkling of the skin), furrowing of the face and scalp, periostosis (swelling of periarticular tissue and shaggy periosteal new bone formation of long bones) and digital clubbing (enlargement of fingertips). Other features include excessive sweating, arthralgia and gastrointestinal abnormalities. An overview of all symptoms is provided in table 2.

Table 2. Overview of symptoms

Pachydermoperiostosis (PDP) or primary hypertrophic osteoarthropathy (PHO) is a rare genetic disorder that affects both bones and skin. Other names are idiopathic hypertrophic osteoarthropathy or Touraine-Solente-Golé syndrome. It is mainly characterized by pachydermia (thickening of the skin), periostosis (excessive bone formation) and finger clubbing (swelling of tissue with loss of normal angle between nail and nail bed).

This disease affects relatively more men than women. After onset, the disease stabilizes after about 5–20 years. Life of PDP patients can be severely impaired. Currently, symptomatic treatments are NSAIDs and steroids or surgical procedures.

In 1868, PDP was first described by Friedreich as ‘excessive growth of bone of the entire skeleton’. Touraine, Solente and Golé described PDP as the primary form of bone disease hypertrophic osteoarthropathy in 1935 and distinguished its three known forms.

Hypertrophic osteoarthropathy (also known as hypertrophic pulmonary osteoarthropathy, Bamberger–Marie syndrome or Osteoarthropathia hypertrophicans) is a medical condition combining clubbing and periostitis of the small hand joints, especially the distal interphalangeal joints and the metacarpophalangeal joints. Distal expansion of the long bones as well as painful, swollen joints and synovial villous proliferation are often seen. The condition may occur alone (primary), or it may be secondary to diseases like lung cancer. It is especially associated with non-small cell lung carcinoma. These patients often get clubbing and increased bone deposition on long bones. Their presenting symptoms are sometimes only clubbing and painful ankles.

Hypertrophic osteoarthropathy is one of many distant effect disorders due to cancer, with lung cancer being the most common cause but also occurring with ovarian or adrenal malignancies. A distant effect disorder, or a paraneoplastic syndrome, affects distant areas and thus is not related to local compression or obstruction effects from the tumor. Other paraneoplastic syndromes include hypercalcemia, SIADH, Cushing's syndrome and a variety of neurological disorders.

Acroosteolysis is resorption of the distal bony phalanges. Acroosteolysis has two patterns of resorption in adults: diffuse and bandlike.

The diffuse pattern of resorption has a widely diverse differential diagnosis which includes: pyknodysostosis, collagen vascular disease and vasculitis, Raynaud's neuropathy, trauma, epidermolysis bullosa, psoriasis, frostbite, sarcoidosis, hypertrophic osteoarthropathy, acromegaly, and advanced leprosy.

The bandlike pattern of resorption may be seen with polyvinyl chloride exposure and Hadju-Cheney syndrome.

A mnemonic commonly used for acro-osteolysis is PINCHFO.

Pyknodysostosis, Psoriasis,

Injury (thermal burn, frostbite),

Neuropathy (diabetes),

Collagen vascular disease (scleroderma, Raynaud's),

Hyperparathyroidism,

Familial (Hadju-Cheney, progeria),

Occupational (polyvinyl exposure),

Acroosteolysis may be associated with minimal skin changes or with ischemic skin lesions that may result in digital necrosis.

This condition is a skeletal dysplasia characterized by short stature, mild brachydactyly, kyphoscoliosis, abnormal gait, enlarged knee joints, precocious osteoarthropathy, platyspondyly, delayed epiphyseal ossification, mild metaphyseal abnormalities, short stature and short and bowed legs. Intelligence is normal.

Some patients may manifest premature pubarche and hyperandrogenism.

Other features that may form part of the syndrome include precocious costal calcification, small iliac bones, short femoral necks, coxa vara, short halluces and fused vertebral bodies.

A hypertrophic scar is a cutaneous condition characterized by deposits of excessive amounts of collagen which gives rise to a raised scar, but not to the degree observed with keloids. Like keloids, they form most often at the sites of pimples, body piercings, cuts and burns. They often contain nerves and blood vessels. They generally develop after thermal or traumatic injury that involves the deep layers of the dermis and express high levels of TGF-β.

Lipohypertrophy is a medical term that refers to a lump under the skin caused by accumulation of extra fat at the site of many subcutaneous injections of insulin. It may be unsightly, mildly painful, and may change the timing or completeness of insulin action. It is a common, minor, chronic complication of diabetes mellitus.

Typical injection site hypertrophy is several inches or cm across, smoothly rounded, and somewhat firmer than ordinary subcutaneous fat. There may be some scar tissue as well, but the major component is adipose tissue, as insulin exerts a hypertrophic effect on adipose cells. To avoid lipohypertrophy, persons with diabetes mellitus who inject insulin daily for an extended period of time are advised to "rotate" their injections among several areas (usually upper, outer arms, outer thighs, abdomen below and around the umbilicus, and the upper parts of the buttocks). Rotation charts are often provided as part of diabetes education to help prevent lipohypertrophy.

Lipohypertrophy usually will gradually disappear over months if injections in the area are avoided.

It is a common misconception that the lump is largely scar tissue, as injection site hypertrophy is much rarer and milder with injections of other hormones and medications which lack the specific ability of insulin to stimulate adipose hypertrophy.

In a sense, the "opposite" of injection site lipohypertrophy is injection site lipoatrophy, in which the subcutaneous fat around an injected area "melts away" over a few weeks or months, leaving unsightly, well-demarcated depressions in the skin. The mechanism of this local lipoatrophy is not understood and may involve autoimmunity or local inflammation.

The clinical presentation is variable but includes

- developmental and growth delay

- athletic muscular built

- skeletal anomalies

- joint stiffness

- characteristic facial appearance

- deafness

- variable cognitive deficits

- tracheal stenosis

- aortic stenosis

- pyloric stenosis

The facial abnormalities include:

- blepharophimosis (an abnormally narrow gap between the upper and lower eyelids)

- maxillary hypoplasia (underdevelopment of the upper jaw)

- prognathism (prominent lower jaw)

The skeletal abnormalities include:

- short stature

- square body shape

- broad ribs

- iliac hypoplasia

- brachydactyly

- flattened vertebrae

- thickened calvaria

Congenital heart disease and undescended testes have also been reported in association with this syndrome.

The incidence of this disease is not precisely known but it is considered to be rare (< 1/10 population). It has been reported in 15 families to date mostly from Canada, Finland and France.

This disease usually presents between the ages of 5 to 10 years old. The usual picture is with weakness involving the upper legs and affects activities such as running and climbing stairs. As the condition progresses, patients tend to experience weakness in their lower legs and arms. Some remain able to walk in advanced age, while others require assistance in adulthood.

Clinical findings include erythema, edema and increased temperature in the affected joint. In neuropathic foot joints, plantar ulcers may be present. Note that it is often difficult to differentiate osteomyelitis from a Charcot joint, as they may have similar tagged WBC scan and MRI features (joint destruction, dislocation, edema). Definitive diagnosis may require bone or synovial biopsy.

X-linked myopathy with excessive autophagy (XMEA) is a rare childhood onset disease characterized by slow progressive vacuolation and atrophy of skeletal muscle. There is no known cardiac or intellectual involvement.

A periosteal reaction can result from a large number of causes, including injury and chronic irritation due to a medical condition such as hypertrophic osteopathy, bone healing in response to fracture, chronic stress injuries, subperiosteal hematomas, osteomyelitis, and cancer of the bone. It may also occur as part of thyroid acropachy, a severe sign of the autoimmune thyroid disorder Grave's disease.

Other causes include Menkes kinky hair syndrome and hypervitaminosis A.

It can take about three weeks to appear.

The clinical presentation varies depending on the stage of the disease from mild swelling to severe swelling and moderate deformity. Inflammation, erythema, pain and increased skin temperature (3–7 degrees Celsius) around the joint may be noticeable on examination. X-rays may reveal bone resorption and degenerative changes in the joint. These findings in the presence of intact skin and loss of protective sensation are pathognomonic of acute Charcot arthropathy.

Roughly 75% of patients experience pain, but it is less than what would be expected based on the severity of the clinical and radiographic findings.

A periosteal reaction is the formation of new bone in response to injury or other stimuli of the periosteum surrounding the bone. It is most often identified on X-ray films of the bones.

Mechanical tension on a wound has been identified as a leading cause for hypertrophic scar formation.

When a normal wound heals, the body produces new collagen fibres at a rate which balances the breakdown of old collagen. Hypertrophic scars are red and thick and may be itchy or painful. They do not extend beyond the boundary of the original wound, but may continue to thicken for up to six months. They usually improve over one or two years, but may cause distress due to their appearance or the intensity of the itching; they can also restrict movement if they are located close to a joint.

Some people have an inherited tendency to this type of scarring, for example, those with Ehlers–Danlos syndrome, classic type. It is not possible to completely prevent hypertrophic scars, so those with a history of them should inform their doctor or surgeon if they need surgery. Scar therapies may speed up the process of change from a hypertrophic scar to a flatter, paler one.

Spondyloepimetaphyseal dysplasia, Pakistani type is a form of spondyloepimetaphyseal dysplasia involving "PAPSS2" (also known as "ATPSK2"). The condition is rare.

The presentation of this condition includes a characteristic facies. The cardiac manifestations include patent ductus arteriosus, congenital hypertrophy of the left ventricle, and pericardial effusions.

Neurodevelopmental outcome appears normal, but obsessive traits and anxiety have been reported. It may also be associated with recurrent infections with low immunoglobulin levels and gastric bleeding, and additional possible associations include lymphoedema and heterochromia iridis.

The terms gingival hyperplasia and gingival hypertrophy have been used to describe this topic in the past. These are not precise descriptions of gingival enlargement because these terms are strictly histologic diagnoses, and such diagnoses require microscopic analysis of a tissue sample. Hyperplasia refers to an increased number of cells, and hypertrophy refers to an increase in the size of individual cells. As these identifications obviously cannot be performed with a clinical examination and evaluation of the tissue, the term "gingival enlargement" is more properly applied. Gingival enlargement has been classified according to cause into 5 general groups:

- Inflammatory enlargement

- Drug induced enlargement

- Enlargement associated with systemic diseases or conditions

- Neoplastic enlargement

- False enlargement.

Gingival enlargement, (also termed gingival overgrowth, hypertrophic gingivitis, gingival hyperplasia, or gingival hypertrophy, and sometimes abbreviated to GO), is an increase in the size of the gingiva (gums). It is a common feature of gingival disease. Gingival enlargement can be caused by a number of factors, including inflammatory conditions and the side effects of certain medications. The treatment is based on the cause. A closely related term is epulis, denoting a localized tumor (i.e. lump) on the gingiva.

Spinal osteoarthropathy (Charcot's Disease) is a rare disease affecting reptiles (including snakes and lizards) which causes abnormal bone growth on vertebrae, giving the reptile a lumpy appearance. The growth of animals with this disease is limited (a python may only grow long), and their life spans are greatly shortened.

The movement of reptiles with this ailment appears jittery and wooden, and the head movement will be greatly restricted. The condition worsens as the patient ages; the end result is a reptile fused together by its own bones. They are usually euthanized well before this stage, but in general these animals can live their short lives comfortably with little pain.

Spinal osteoarthropathy can also occur in humans.

Lhermitte–Duclos disease (LDD) (), also called dysplastic gangliocytoma of the cerebellum, is a rare, slowly growing tumor of the cerebellum, a gangliocytoma sometimes considered to be a hamartoma, characterized by diffuse hypertrophy of the granular layer of the cerebellum. It is often associated with Cowden syndrome. It was described by Jacques Jean Lhermitte and P. Duclos in 1920.

The disease usually affects the lower legs or scrotum. The swelling is accompanied by rough nodules or wart-like plaques on the skin. If the disease is not treated, it eventually results in pain and immobility.

Though not always present, the cardinal characteristics of this multi-system disorder include: cardiomyopathy (dilated or hypertrophic, possibly with left ventricular noncompaction and/or endocardial fibroelastosis), neutropenia (chronic, cyclic, or intermittent), underdeveloped skeletal musculature and muscle weakness, growth delay, exercise intolerance, cardiolipin abnormalities, and 3-methylglutaconic aciduria.

It can be associated with stillbirth.

Barth syndrome is manifested in a variety of ways at birth. A majority of BTHS patients are hypotonic at birth, show signs of cardiomyopathy within the first few months of life, and experience a deceleration in growth in the first year, despite adequate nutrition. As patients progress into childhood, their height and weight lag significantly behind other children. While most patients express normal intelligence, a high proportion of BTHS patients also express mild or moderate learning disabilities. Physical activity is also hindered due to diminished muscular development and muscular hypotonia. Many of these disorders are resolved after puberty. Growth accelerates during puberty, and many patients reach a normal adult height.

Cardiomyopathy is one of the more severe manifestations of BTHS. The myocardium is dilated, reducing the systolic pump of the ventricles. For this reason, most BTHS patients have left myocardial thickening (hypertrophy). While cardiomyopathy can be life-threatening, it is commonly resolved or substantially improved in BTHS patients after puberty.

Neutropenia is another deadly manifestation of BTHS. Neutropenia is a granulocyte disorder that results in a low production of neutrophils, the body’s primary defenders against bacterial infections. Surprisingly, however, BTHS patients have relatively fewer bacterial infections than other patients with neutropenia.

Main clinical signs and symptoms include:

- headache

- movement disorders

- tremor

- visual disturbances

- abnormal EEG

- Diplopia

Patients with Lhermitte–Duclos disease and Cowden's syndrome may also have multiple growths on skin. The tumor, though benign, may cause neurological injury including abnormal movements.

MICROSCOPY(lhermitte-duclos disease)

1>Enlarged circumscribed cerebellar folia

2>internal granular layer is focally indistinct and is occupied by large ganglion cells

3>myelinated tracks in outer molecular layer

4>underlying white matter is atrophic and gliotic