Affected males develop generalized reticular hyper pigmentation in early childhood.

Hair often looks bedraggled or brushed backwards, hanging low on the forehead.

Among the associated extracutaneous manifestations are described:

- Respiratory infections

- Dyskeratosis corneal photophobia

- Hypohidrosis with large deficit of thermoregulation

- Growth retardation

- Gastrointestinal disorders

- Kidney disease

- Kidney stones

- Urinary infections

- Webbed feet or hands

- Electrolyte imbalance

- Retinitis pigmentosa

- Lymphoedema

- Thyroid abnormalities

Each patient shows some of the symptoms listed above. Not every sick person will show all of the listed symptoms.

In females the disease is characterized by skin rashes linear hyper pigmentation following the Blaschko's lines, morphologically similar to stage 3 pigment incontinence. There are no systemic manifestations associated with XLPDR in females.

The age of onset is almost always before 3 months of age. Many infants are born preterm (1/3 cases) and dysmature. The babies are frequently small for dates. The placenta may be abnormal with non-specific inflammation on histology. Umbilical cord anomalies have occasionally been reported. In severe cases, signs in the brain may be detected on prenatal ultrasound.

The presentation is pleiomorphic, making the diagnosis difficult, but the most common features of this disease involve the skin, joints, and central nervous system.

All have a maculopapular urticarial skin rash that is often present at birth (75% cases). It is probably more correctly described as an urticarial-like rash. The presence of the rash varies with time, and biopsy of these skin lesions shows a perivascular inflammatory infiltrate including granulocytes.

In about 35-65% of cases, arthritis occurs. Joint signs are variably expressed and can lead to transient swelling without sequelae between crises, or to unpredictable anomalies of growth cartilage and long bones epiphyses suggestive of a pseudo-tumour. Biopsies reveal hypertrophic cartilage without inflammatory cells. This most commonly affects the large joints (knees, ankles, elbows, and wrists) but may also involve the small joints of the hands and feet. It is usually bilateral and painful. A common and characteristic feature is giant kneecaps. Severe cases may result in contractures (joint deformities).

Most patients eventually have neurological problems. These manifest themselves in three principal ways: chronic meningitis, involvement of both the optic tract and eye, and sensorineural hearing loss. The chronic meningitis presents with the features of chronically raised intracranial pressure: headaches, vomiting, ventriculomegaly, hydrocephalus, macromegaly, cerebral atrophy, and optic atrophy. Some of these features may be evidenced on prenatal ultrasound. In 50% of cases, intellectual deficit occurs. Seizures occur in 25% of cases, but other manifestations are rare. Histological examination shows infiltration of the meninges with polymorphs.

Ocular manifestations occur in 80% of cases and include uveitis (70%), papillary involvement, conjunctivitis, and optical neuritis. If untreated, these may result in blindness (25%). The sensorineural hearing loss occurs in 75%, and tends to be progressive leading to deafness in 20% of cases.

Almost all children are remarkably short and have growth delay. Fever is extremely common but inconstant and is most often mild. Anemia is frequent. Other findings that have been reported include macrocephaly (95%), large fontanelle, prominent forehead, flattening of the nasal bridge (saddleback nose), short and thick extremities, and finger clubbing. The liver and/or spleen may be enlarged. Lymph node enlargement may also be present.

Later in life, secondary amyloidosis may occur. Delayed puberty and secondary amenorrhoea are not uncommon. Hoarseness due to inflammation of the laryngeal cartilage has also been reported.

X-linked reticulate pigmentary disorder (also known as "familial cutaneous amyloidosis", "Partington amyloidosis", "Partington cutaneous amyloidosis", "Partington syndrome type II", "reticulate pigmentary disorder", and "X-linked reticulate pigmentary disorder with systemic manifestations") is a cutaneous condition that has been described in adult women that had linear streaks of hyperpigmentation and in which male patients manifested a reticulated mottled brown pigmentation of the skin, which, on biopsy, demonstrated dermal deposits of amyloid.

The syndrome is also referred with the acronym X-Linked-PDR or even XLPRD.It's a very rare disease, genetically determined, with a chronic course.

It was characterized in 1981. Mutation of the "POLA1" gene leads to loss of expression of the catalytic subunit of DNA polymerase-α and is responsible for XLPDR. Loss of POLA1 expression results in reduced levels of RNA:DNA hybrids in the cytosol and unexpectedly triggers aberrant immune responses (e.g. type I interferon production) which at least in part can account for the symptoms associated with XLPDR.

This disorder is characterized by a reduction and loss of subcutaneous fat and collagen of the hands and feet, above all. It can be defined it as a mild, nonprogressive, congenital form of premature skin senility due to the disappearance of the fatty tissue directly under the skin.

More precisely, skin lesions deal with large, fixed, geographic and symmetrical fine scaly recessive erythematous plaques distributed over the dorsal side of distal extremities. Skin lesions can be associated with osteoarticular alterations.

Other outcomes and observations may include abnormally small hands and feet with unusually prominent veins on the upper trunk (chest), short stature, and, sometimes, abnormally small jaw (micrognathia). Most of the cases analyzed show atrophy of the skin at the tip of the nose, which gives a sculptural appearance.The nails may be dystrophic or thick, but, most of the time, they are normal.

In the skin histopathology, there is atrophy of the dermis and subcutaneum. The collagen fibers are loose and dispersed, and the elastic fibers are always fragmented.

However, the epidermis is not affected.

Although some patients present clinical features similar to those of progeria and metageria, they do not usually show generalized atherosclerosis. Therefore, they do not usually have premature myocardic or coronary disease.

Clinical diagnostic features are lifelong eruptions of pityriasis versicolor-like macules, flat wart-like papules, one to many cutaneous horn-like lesions, and development of cutaneous carcinomas.

Patients present with flat, slightly scaly, red-brown macules on the face, neck, and body, recurring especially around the penial area, or verruca-like papillomatous lesions, seborrheic keratosis-like lesions, and pinkish-red plane papules on the hands, upper and lower extremities, and face. The initial form of EV presents with only flat, wart-like lesions over the body, whereas the malignant form shows a higher rate of polymorphic skin lesions and development of multiple cutaneous tumors.

Generally, cutaneous lesions are spread over the body, but some cases have only a few lesions which are limited to one extremity.

Shabbir syndrome (also known as laryngo–onycho–cutaneous syndrome) is a cutaneous condition inherited in an autosomal recessive fashion.

It was characterized by Shabbir in 1986.

It may be associated with "LAMA3".

Age: The mucocutaneous features of DKC typically develop between ages 5 and 15 years. The median age of onset of the peripheral cytopenia is 10 years.

Sex: The male-to-female ratio is approximately 3:1.

Physical: The triad of reticulated hyperpigmentation of the skin, nail dystrophy, and leukoplakia characterizes DKC. The syndrome is clinically heterogeneous; in addition to the diagnostic mucocutaneous features and bone marrow failure, affected individuals can have a variety of other clinical features.

Cutaneous findings:

The primary finding is abnormal skin pigmentation, with tan-to-gray hyperpigmented or hypopigmented macules and patches in a mottled or reticulated pattern. Reticulated pigmentation occurs in approximately 90% of patients. Poikilodermatous changes with atrophy and telangiectasia are common.

The cutaneous presentation may clinically and histologically resemble graft versus host disease. The typical distribution involves the sun-exposed areas, including the upper trunk, neck, and face. Other cutaneous findings may include alopecia of the scalp, eyebrows, and eyelashes; premature graying of the hair; hyperhidrosis; hyperkeratosis of the palms and soles; and adermatoglyphia (loss of dermal ridges on fingers and toes).

Nail findings:

Nail dystrophy is seen in approximately 90% of patients, with fingernail involvement often preceding toenail involvement.

Progressive nail dystrophy begins with ridging and longitudinal splitting. Progressive atrophy, thinning, pterygium, and distortion eventuate in small, rudimentary, or absent nails.

Mucosal findings:

Mucosal leukoplakia occurs in approximately 80% of patients and typically involves the buccal mucosa, tongue, and oropharynx. The leukoplakia may become verrucous, and ulceration may occur. Patients also may have an increased prevalence and severity of periodontal disease.

Other mucosal sites may be involved (e.g., esophagus, urethral meatus, glans penis, lacrimal duct, conjunctiva, vagina, anus). Constriction and stenosis can occur at these sites, with subsequent development of dysphagia, dysuria, phimosis, and epiphora.

Bone marrow failure:

Approximately 90% have peripheral cytopenia of one or more lineages. In some cases, this is the initial presentation, with a median age of onset of 10 years.

Bone marrow failure is a major cause of death, with approximately 70% of deaths related to bleeding and opportunistic infections as a result of bone marrow failure.

Pulmonary complications:

Approximately 20% of individuals with DKC develop pulmonary complications, including pulmonary fibrosis and abnormalities of pulmonary vasculature.

The recommendation is that DKC patients avoid taking drugs with pulmonary toxicity (e.g., busulfan) and that they have their lungs shielded from radiation during BMT.

Increased risk of malignancy:

Patients have an increased prevalence of malignant mucosal neoplasms, particularly squamous cell carcinoma of the mouth, nasopharynx, esophagus, rectum, vagina, or cervix. These often occur within sites of leukoplakia.

The prevalence of squamous cell carcinoma of the skin is also increased. Other malignancies reported include Hodgkin lymphoma, adenocarcinoma of the gastrointestinal tract, and bronchial and laryngeal carcinoma.

Malignancy tends to develop in the third decade of life.

Neurologic system findings: Patients may have learning difficulties and mental retardation.

Ophthalmic system findings: DKC reportedly is associated with conjunctivitis, blepharitides, and pterygium. Lacrimal duct stenosis resulting in epiphora (i.e., excessive tearing) occurs in approximately 80% of patients.

Skeletal system findings: Patients may have mandibular hypoplasia, osteoporosis, avascular necrosis, and scoliosis.

Gastrointestinal system findings: These may include esophageal webs, hepatosplenomegaly, enteropathy, and cirrhosis.

Genitourinary system findings:: Hypospastic testes, hypospadias, and ureteral stenosis are reported.

Female carriers: Female carriers of DKC may have subtle clinical features. One study showed that 3 of 20 female carriers had clinical features that included a single dystrophic nail, a patch of hypopigmentation, or mild leukoplakia.

Neonatal-onset multisystem inflammatory disease (abbreviated NOMID, also known as chronic infantile neurologic cutaneous and articular syndrome, or CINCA) is a rare genetic periodic fever syndrome which causes uncontrolled inflammation in multiple parts of the body starting in the newborn period. Symptoms include skin rashes, severe arthritis, and chronic meningitis leading to neurologic damage. It is one of the cryopyrin-associated periodic syndromes.

NOMID can result from a mutation in the "CIAS1" gene (also known as "NLRP3" gene), which helps control inflammation. Mutations in this gene also cause familial cold urticaria and Muckle–Wells syndrome. NOMID has been successfully treated with the drug anakinra.

This syndrome is also known as the Prieur–Griscelli syndrome as it was first described by these authors in 1981.

The syndromes within CAPS overlap clinically, and patients may have features of more than one disorder. In a retrospective cohort of 136 CAPS patients from 16 countries, the most prevalent clinical features were fever (84% of cases, often with concurrent constitutional symptoms such as fatigue, malaise, mood disorders or failure to thrive), skin rash (either urticarial or maculopapular rash; 97% of cases) especially after cold exposure, and musculoskeletal involvement (myalgia, arthralgia, and/or arthritis, or less commonly joint contracture, patellar overgrowth, bone deformity, bone erosion and/or osteolytic lesion; 86% of cases). Less common features included ophthalmological involvement (conjunctivitis and/or uveitis, or less commonly optic nerve atrophy, cataract, glaucoma or impaired vision; 71% of cases), neurosensory hearing loss (42% of cases), neurological involvement (morning headache, papilloedema, and/or meningitis, or less commonly seizure, hydrocephalus or mental retardation; 40% of cases), and AA amyloidosis (4% of cases). Age of onset is typically in infancy or early childhood. In 57% of cases, CAPS had a chronic phenotype with symptoms present almost daily, whereas the remaining 43% of patients experienced only acute episodes. Up to 56% of patients reported a family history of CAPS. Previous studies confirm these symptoms, although the exact reported rates vary.

Hemangiomas associated with PHACE Syndrome are usually small or not visible at birth, but are easier to see during the first days to weeks of life. They can grow rapidly. Hemangiomas linked with PHACE Syndrome tend to cover a large area of the face, head or neck, either as one lesion or as many single lesions.

Acrogeria (also known as Gottron's syndrome) is a cutaneous condition characterized by premature aging, more especially in the form of unusually fragile, thin skin on the hands and feet (distal extremities). The prefix "acro" stems from the Greek "akros" which alludes to "extremity, tip" while the suffix "geria" comes from the Greek "gerôn" which means "elder".

This is one of the classic congenital premature aging syndromes, occurring early in life, among which are: pangeria (Werner's syndrome), progeria (Hutchinson–Gilford's syndrome) and acrogeria (Gottron's syndrome) and was characterized in 1940. Onset is in early childhood, it progresses over the next few years and then remains stable over time with morphology, colour and site remaining constant. A bruising tendency has been observed.

It is believed that Gottron syndrome may affect more females than males. Approximately forty cases have been reported in the medical literature, since the discovery of the disorder.

This condition is characterized by:

- a diffuse infiltration of all the skin which never transforms into nodule

- a complete alopecia of eyebrows and eyelashes and body hair

- an anhydrotic and dysesthesic zones of the skin

- a peculiar type of lepra reaction named Lucio's phenomenon or necrotic erythema

Lucio's phenomenon consists of well-shaped erythematous spots which later become necrotic with scabs, ulcerations and scars. These lesion usually on the lower extremities and may be extensive They are frequently painful. Rarely it may be fatal.

Epidermodysplasia verruciformis (EV), also known as treeman syndrome, is an extremely rare autosomal recessive hereditary skin disorder associated with a high risk of skin cancer. It is characterized by abnormal susceptibility to human papillomaviruses (HPVs) of the skin. The resulting uncontrolled HPV infections result in the growth of scaly macules and papules, particularly on the hands and feet. It is typically associated with HPV types 5 and 8, which are found in about 80% of the normal population as asymptomatic infections, although other types may also contribute.

The condition usually has an onset of between the ages of one and 20 but can occasionally present in middle age. The condition is also known as Lewandowsky–Lutz dysplasia – named after the physicians who first documented it, Felix Lewandowsky and Wilhelm Lutz.

Typically not diagnosed until late childhood or later, Bonnet–Dechaume–Blanc syndrome usually presents itself with a combination of central nervous system features (midbrain), ophthalmic features (retina), and facial features. The degree of expression of the syndrome's components varies both clinically and structurally. Common symptoms that lead to diagnosis are headaches, retro-orbital pain and hemianopia.

The ophthalmic features of the Bonnet–Dechaume–Blanc syndrome occur as retinal arteriovenous malformation (AVMs). There are three categories of AVMs that are categorized depending on the severity of the malformation. The first category consists of the patient having small lesions that usually are asymptomatic. The second category, more severe than the first, is when the patient’s malformation is missing a connecting capillary. The missing capillary is meant to serve as a link between an artery and a vein; without it, edemas, hemorrhages, and visual impairments can result. Category three, the most severe, occurs when the patient’s malformations are so severe that the dilated vessels cause no distinction between artery and vein. When the symptoms are this severe, the patient has a significantly increased risk of developing vision loss. Since the retinal lesions categorized vary from large vascular malformations that affect a majority of the retina to malformations that are barely visible, the lesions cause a wide range of symptoms including decrease in visual sharpness, proptosis, pupillary defects, optic degeneration and visual field defects. The most common type of visual field impairment due to AVMs is homonymous hemianopia. Homonymous hemianopia typically presents unilaterally, but bilateral cases have been reported as well.

The extent of the central nervous system (CNS) features/symptoms of Bonnet–Dechaume–Blanc syndrome is highly dependent of the location of the cerebral AVMs and the extent of the malformation. The most common symptom affecting the CNS is an intracranial hemangioma in the midbrain. Along with hemangiomas, the malformations result in severe headaches, cerebral hemorrhages, vomiting, meningism, seizures, acute strokes or progressive neurological deficits due to acute or chronic ischaemia caused by arteriovenous shunting.

The distinguishable facial features that result from Bonnet–Dechaume–Blanc syndrome vary from case to case. A person showing signs of the syndrome may display faint skin discoloration, nevi and angiomas of the skin. Some patients with this disorder also present with high flow arteriovenous malformations of the maxillofacial or mandibular (jaw) regions. Another facial indicator of this disease is malformations affecting the frontal and/or maxillary sinuses.

Melanoma with features of a Spitz nevus (also known as a "Spitzoid melanoma") is a cutaneous condition characterized histologically with tissue similar to a spitz nevus and with overall symmetry and a dermal nodule of epithelioid melanocytes that do not mature with progressively deeper dermal extension.

Enchondromatosis is a form of osteochondrodysplasia characterized by a proliferation of enchondromas.

Ollier disease can be considered a synonym for enchondromatosis. Maffucci syndrome is enchondromatosis with hemangiomatosis.

DKC can be characterized by cutaneous pigmentation, premature graying, of the nails, leukoplakia of the oral mucosa, continuous lacrimation due to atresia of the lacrimal ducts, often thrombocytopenia, anemia, testicular atrophy in the male carriers, and predisposition to cancer. Many of these symptoms are characteristic of geriatrics, and those carrying the more serious forms of the disease often have significantly shortened lifespans.

As it grows, the hemangioma can break down skin, distort facial features or get in the way of other vital functions, such as breathing, vision, and hearing. Other complications will depend on what other structures are involved. These could include developmental delay, seizures, headaches, and abnormal muscle tone if the brain is involved.

Progressive osseous heteroplasia is a cutaneous condition characterized by cutaneous or subcutaneous ossification.

According to the Progressive Osseous Heteroplasia Association:

It is associated with "GNAS".

Benign neonatal hemangiomatosis is a cutaneous condition in infants, characterized by multiple cutaneous lesions without evident visceral hemangiomas.

Florid cutaneous papillomatosis (also known as the Schwartz-Burgess syndrome) is an obligate paraneoplastic syndrome.

FCP begins as the sudden onset of numerous cutaneous papillomas that are clinically indistinguishable from viral warts. The papillomas range from 1 to 3 mm in diameter may spread to involve the entire body, including the face. Pruritus, which may sometimes precede the onset of FCP, is evident in the affected regions in about half of patients. Evaluation of a skin biopsy clearly distinguishes FCP from viral warts.

FCP is associated with underlying cancer of the breast, bladder, ovary, uterus, prostate, and lung. Other associated underlying malignancies include squamous cell carcinomas and lymphomas such as non-Hodgkin's lymphoma.

FCP is sometimes seen together with other signs of internal cancer, especially malignant acanthosis nigricans, tripe palms, Leser–Trélat sign, and hypertrichosis lanuginosa acquisita. FCP tends to improve in association with surgical or chemotherapeutic therapy of the underlying internal cancer. A recurrence or exacerbation of FCP may be linked with tumor regrowth or metastatic spread.

Haber syndrome is a cutaneous disorder of hyperpigmentation characterized by reticulated pigmentation of the person's skin. A rare genodermatosis, its key features include "rosacea-like facial eruption[,] reticulated hyperpigmentation of major flexures, comedones on the back and neck, and pitted facial scars."

Usually, pseudoxanthoma elasticum affects the skin first, often in childhood but frequently later. Small, yellowish papular lesions form and cutaneous laxity mainly affects the neck, axillae (armpits), groin, and flexural creases (the inside parts of the elbows and knees). Skin may become lax and redundant. Many individuals have "oblique mental creases" (diagonal grooves of the chin).

PXE first affects the retina through a dimpling of the Bruch membrane (a thin membrane separating the blood vessel-rich layer from the pigmented layer of the retina), that is only visible during ophthalmologic examinations. This is called peau d'orange (a French term meaning that the retina resembles the skin of an orange). Eventually the mineralization of the elastic fibers in the Bruch membrane create cracks (angioid streaks) that radiate out from the optic nerve. Angioid streaks themselves do not cause distortion of vision, even if they cross into the foveal area. This symptom is present in almost all PXE patients and is usually noticed a few years after the onset of cutaneous . These cracks may allow small blood vessels that were originally held back by Bruch's membrane to penetrate the retina. These blood vessels sometimes leak, and these retinal hemorrhages may lead to the loss of central vision. Vision loss is a major issue in many PXE patients.

PXE may affect the gastrointestinal and cardiovascular systems. In the digestive tract, the principal symptom is gastrointestinal bleeding, usually from the stomach. This occurs in a very small number of patients. In the circulatory system, intermittent claudication (leg pain during walking which resolves at rest) is a prominent feature, although at later stages coronary artery disease may develop, leading to angina and myocardial infarction (heart attack) may occur.

Bonnet–Dechaume–Blanc syndrome, also known as Wyburn-Mason syndrome, is a rare congential arteriovenous malformation of the brain, retina or facial nevi. The syndrome has a number of possible symptoms and can affect the skin, bones, kidneys, muscles, and gastrointestinal tract. When the syndrome affects the brain, people can experience severe headaches, seizures, acute stroke, meningism and progressive neurological deficits due to acute or chronic ischaemia caused by arteriovenous shunting.

As for the retina, the syndrome causes retinocephalic vascular malformations that tend to be present with intracranial hemorrhage and lead to decreased visual acuity, proptosis, pupillary defects, optic atrophy, congestion of bulbar conjunctiva, and visual field defects. Retinal lesions can be unilateral and tortuous, and symptoms begin to appear in the second and third decades of life.

The syndrome can present cutaneous lesions, or skin with different texture, thickness, and color, usually on the face. The facial features caused by the syndrome vary from slight discoloration to extensive nevi and angiomas of the skin. In some cases, the frontal and maxillary sinus can present problems in the subject due to the syndrome.

There have only been 52 reported cases of patients with Bonnet–Dechaume–Blanc syndrome as of 2012. Symptoms are rarely noticed in children and the syndrome is often diagnosed in late childhood or early adulthood when visual impairment is noticed. Fluorescein angiography is commonly used to diagnose the syndrome.

There have been several methods in treating patients who display Bonnet–Dechaume–Blanc syndrome. However, which method seems to work the most is within argument. Patients with intracranial lesions have been treated with surgical intervention and in some cases, this procedure has been successful. Other treatments include embolization, radiation therapy, and continued observation.

With limited research on Bonnet–Dechaume–Blanc syndrome, researchers have focused on the clinical and radiological findings rather than how to manage this rare and non-heritable syndrome.

The diffuse leprosy of Lucio and Latapí, also known as diffuse lepromatous leprosy or "pretty leprosy" is a clinical variety of lepromatous leprosy. It was first described by Lucio and Alvarado in 1852 and re-identified by Latapí in 1936. It is common in Mexico (23% leprosy cases) and in Costa Rica and very rare in other countries.