The skin is normal at birth. Between 3 and 6 months of age, the affected carrier develops poikiloderma on the cheeks. This characteristic "rash" that all RTS carriers have can develop on the arms, legs and buttocks. "Poikiloderma consists of areas of increased and decreased pigmentation, prominent blood vessels, and thinning of the skin."

Rothmund–Thomson syndrome (RTS), also known as poikiloderma atrophicans with cataract or poikiloderma congenitale, is a rare autosomal recessive skin condition originally described by August von Rothmund (1830–1906) in 1868. Matthew Sydney Thomson (1894–1969) published further descriptions in 1936.

There have been several reported cases associated with osteosarcoma. A hereditary genetic basis, mutations in the DNA Helicase "RECQL4" gene, causing problems during initiation of DNA replication has been implicated in the syndrome

Ectrodactyly, split hand, cleft hand, derived from the Greek "ektroma" (abortion) and "daktylos" (finger) involves the deficiency or absence of one or more central digits of the hand or foot and is also known as split hand/split foot malformation (SHFM). The hands and feet of people with ectrodactyly are often described as "claw-like" and may include only the thumb and one finger (usually either the little finger, ring finger, or a syndactyly of the two) with similar abnormalities of the feet.

It is a rare form of a congenital disorder in which the development of the hand is disturbed. It is a type I failure of formation – longitudinal arrest. The central ray of the hand is affected and usually appears without proximal deficiencies of nerves, vessels, tendons, muscles and bones in contrast to the radial and ulnar deficiencies. The cleft hand appears as a V-shaped cleft situated in the centre of the hand. The digits at the borders of the cleft might be syndactilyzed, and one or more digits can be absent. In most types, the thumb, ring finger and little finger are the less affected parts of the hand. The incidence of cleft hand varies from 1 in 90,000 to 1 in 10,000 births depending on the used classification. Cleft hand can appear unilateral or bilateral, and can appear isolated or associated with a syndrome.

Split hand/foot malformation (SHFM) is characterized by underdeveloped or absent central digital rays, clefts of hands and feet, and variable syndactyly of the remaining digits. SHFM is a heterogeneous condition caused by abnormalities at one of multiple loci, including SHFM1 (SHFM1 at 7q21-q22), SHFM2 (Xq26), SHFM3 (FBXW4/DACTYLIN at 10q24), SHFM4 (TP63 at 3q27), and SHFM5 (DLX1 and DLX 2 at 2q31). SHFM3 is unique in that it is caused by submicroscopic tandem chromosome duplications of FBXW4/DACTYLIN. SHFM3 is considered 'isolated' ectrodactyly and does not show a mutation of the tp63 gene.

Ectrodactyly can be caused by various changes to 7q. When 7q is altered by a deletion or a translocation ectrodactyly can sometimes be associated with hearing loss. Ectrodactyly, or Split hand/split foot malformation (SHFM) type 1 is the only form of split hand/ malformation associated with sensorineural hearing loss.

The condition affects all major structures within the thorax and abdomen. Generally, the organs are simply transposed through the sagittal plane. The heart is located on the right side of the thorax, the stomach and spleen on the right side of the abdomen and the liver and gall bladder on the left side. The heart's normal right atrium occurs on the left, and the left atrium is on the right. The lung anatomy is reversed and the left lung has three lobes while the right lung has two lobes. The intestines and other internal structures are also reversed from the normal, and the blood vessels, nerves, and lymphatics are also transposed.

If the heart is swapped to the right side of the thorax, it is known as "situs inversus with dextrocardia" or "situs inversus totalis". If the heart remains on the normal left side of the thorax, a much more rare condition (1 in 2,000,000 of the general population), it is known as "situs inversus with levocardia" or "situs inversus incompletus".

Situs inversus of the optic disc may occur unilaterally or bilaterally, associated with reduced binocularity and stereoacuity resembling monofixation syndrome. It is characterized by emergence of the retinal vessels in an anomalous direction (from the nasal rather than the temporal aspect) with dysversion (tilt) of the optic disc.

In the absence of congenital heart defects, individuals with situs inversus are phenotypically normal, and can live normal healthy lives, without any complications related to their medical condition. There is a 5–10% prevalence of congenital heart disease in individuals with situs inversus totalis, most commonly transposition of the great vessels. The incidence of congenital heart disease is 95% in situs inversus with levocardia.

Many people with situs inversus totalis are unaware of their unusual anatomy until they seek medical attention for an unrelated condition, such as a rib fracture or a bout of appendicitis. The condition may also be discovered during the administration of certain medicines or during tests such as a Barium meal or enema. The reversal of the organs may then lead to some confusion, as many signs and symptoms will be on the atypical side. For example, if an individual with situs inversus develops appendicitis, they will present to the physician with lower left abdominal pain, since that is where their appendix lies. Thus, in the event of a medical problem, the knowledge that the individual has situs inversus can expedite diagnosis. People with this rare condition should inform their doctors before an examination, so the doctor can redirect their search for heart sounds and other signs. Wearing a medical identification tag can help inform health care providers in the event the person is unable to communicate.

Situs inversus also complicates organ transplantation operations as donor organs will more likely come from situs solitus (normal) donors. As hearts and livers are chiral, geometric problems arise placing an organ into a cavity shaped in the mirror image. For example, a person with situs inversus who requires a heart transplant needs all the vessels to the transplant donor heart reattached to their existing ones. However, the orientation of these vessels in a person with situs inversus is reversed, necessitating steps so that the blood vessels join properly.

Triphalangeal thumb can occur in syndromes but it can also be isolated. The triphalangeal thumb can appear in combination with other malformations or syndromes.

Syndromes include:

- Holt-Oram syndrome

- Aase syndrome

- Blackfan-Diamond syndrome

- Townes-Brocks syndrome

Malformations include:

- Radial polydactyly

- Syndactyly

- Claw-like hand or foot

The triphalangeal thumb has a different appearance than normal thumbs. The appearance can differ widely; the thumb can be a longer thumb, it can be deviated in the radio-ulnar plane (clinodactyly), thumb strength can be diminished. In the case of a five fingered-hand it has a finger-like appearance, with the position in the plane of the four fingers, thenar muscle deficiency, and additional length. There is often a combination with radial polydactyly.

Signs and symptoms of Eisenmenger syndrome include the following:

- Cyanosis (a blue tinge to the skin resulting from lack of oxygen)

- High red blood cell count

- Swollen or clubbed finger tips (clubbing)

- Fainting (also known as syncope)

- Heart failure

- Abnormal heart rhythms

- Bleeding disorders

- Coughing up blood

- Iron deficiency

- Infections (endocarditis and pneumonia)

- Kidney problems

- Stroke

- Gout (rarely) due to increased uric acid resorption and production with impaired excretion

- Gallstones

Eisenmenger's syndrome (or ES, Eisenmenger's reaction, Eisenmenger physiology, or tardive cyanosis) is defined as the process in which a long-standing left-to-right cardiac shunt caused by a congenital heart defect (typically by a ventricular septal defect, atrial septal defect, or less commonly, patent ductus arteriosus) causes pulmonary hypertension and eventual reversal of the shunt into a cyanotic right-to-left shunt. Because of the advent of fetal screening with echocardiography early in life, the incidence of heart defects progressing to Eisenmenger's has decreased.

Eisenmenger's syndrome in a pregnant mother can cause serious complications, though successful delivery has been reported. Maternal mortality ranges from 30% to 60%, and may be attributed to fainting spells, thromboembolism, hypovolemia, hemoptysis or preeclampsia. Most deaths occur either during or within the first weeks after delivery. Pregnant women with Eisenmenger syndrome should be hospitalized after the 20th week of pregnancy - or earlier if clinical deterioration occurs.

Xanthochromism (also called xanthochroism or xanthism) is an unusually yellow pigmentation in an animal. It is often associated with the lack of usual red pigmentation and its replacement with yellow. The cause is usually genetic but may also be related to the animal's diet. A Cornell University survey of unusual-looking birds visiting feeders reported that 4% of such birds were described as xanthochromistic (compared with 76% albinistic). The opposite of xanthochromism, a deficiency in or complete absence of yellow pigment, is known as "axanthism".

Birds exhibiting genetic xanthochromism, especially deliberately bred mutations of several species of parrot in aviculture, are termed "lutinos". Wild birds in which xanthochromism has been recorded include yellow wagtail, wood warbler, Cape May warbler, rose-breasted grosbeak, evening grosbeak, red-bellied woodpecker, scarlet tanager, northern cardinal, great spotted woodpecker, common tailorbird, crimson-breasted shrike, kākāriki and kea.

Lennox–Gastaut syndrome (LGS) is a childhood-onset epilepsy that most often appears between the second and sixth year of life. LGS is characterized by a triad of signs including frequent seizures of multiple types, an abnormal EEG pattern of less than 2.5 Hz slow spike wave activity, and moderate to severe intellectual impairment.

Symptoms of Lafora disease begin to develop during early adolescent years and symptoms progress to worsen as time passes. The first ten years of life there is generally no indication of the presence of the disease. The most common feature of Lafora disease is seizures that have been reported mainly as occipital seizures and myoclonic seizures with some cases of generalized tonic-clonic seizures, atypical absence seizures, and atonic and complex partial seizures. Other symptoms common with the seizures are drop attacks, ataxia, temporary blindness, visual hallucinations, and a quickly-developing and dramatic dementia.

Other common signs and symptoms associated with Lafora disease are behavioral changes because of the frequency of seizures. Over time those affected with Lafora disease have brain changes that cause things such as confusion, speech difficulties, depression, decline in intellectual function, and impaired judgement and memory. If area's of the cerebellum are affected by seizures then it is common to see issues with speech, coordination, and balance in Lafora patients.

For dogs that are affected with Lafora disease, common symptoms are rapid shuddering, shaking, or jerking of the canine's head backwards, high pitched vocalizations that could indicate the dog is panicking, seizures, and as the disease progresses dementia, blindness, and loss of balance.

The age of onset of seizures is typically between three and five, though onset can occur at an earlier or later age. The syndrome shows clear parallels to West syndrome, enough to suggest a connection.

Daily multiple seizures are typical in LGS. Also typical is the broad range of seizures that can occur, larger than that of any other epileptic syndrome. The most frequently occurring seizure type is tonic seizures, which are often nocturnal (90%); the second most frequent are myoclonic seizures, which often occur when the person is over-tired.

Atonic, atypical absence, tonic, complex partial, focalized and tonic–clonic seizures are also common. Additionally, about half of patients will have status epilepticus, usually the nonconvulsive type, which is characterized by dizziness, apathy, and unresponsiveness. The seizures can cause sudden falling (or spasms in tonic, atonic and myoclonic episodes) and/or loss of balance, which is why patients often wear a helmet to prevent head injury.

In addition to daily multiple seizures of various types, children with LGS frequently have arrested/slowed psycho-motor development and behavior disorders.

The syndrome is also characterized by an (between-seizures) EEG featuring slow spike-wave complexes.

Lafora disease, also called Lafora progressive myoclonic epilepsy or MELF, is a fatal autosomal recessive genetic disorder characterized by the presence of inclusion bodies, known as Lafora bodies, within the cytoplasm of the cells in the heart, liver, muscle, and skin. Lafora disease is also a neurodegenerative disease that causes impairment in the development of cerebral cortical neurons and it is a glycogen metabolism disorder.

Dogs can also have the condition. Typically Lafora is rare in American children but has a high occurrence in children from Southern European descent (Italy, France, Spain) and can also be found in children from South Asian countries (Pakistan, India) and even as far south as North Africa. As for canines, Lafora disease can spontaneously occur in any breed but the Miniature Wire Haired Dachshund, Bassett Hound, and the Beagle are predisposed to LD.

Most patients with this disease do not live past the age of twenty-five, and death within ten years of symptoms is usually inevitable. At present, there is no cure for this disease but there are ways to deal with symptoms through treatments and medications.

Cutaneous horns, also known by the Latin name cornu cutaneum, are unusual keratinous skin tumors with the appearance of horns, or sometimes of wood or coral. Formally, this is a clinical diagnosis for a "conical projection above the surface of the skin." They are usually small and localized, but can, in very rare cases be much larger. Although often benign, they can also be malignant or premalignant.

The lesion at the base of the keratin mound is benign in the majority of cases. Malignancy is present in up to 20% of cases, with squamous cell carcinoma being the most common type. The incidence of squamous cell carcinoma increases to 37% when the cutaneous horn is present on the penis. Tenderness at the base of the lesion is often a clue to the presence of a possible underlying squamous cell carcinoma.

Leukodystrophy is one of a group of disorders characterized by degeneration of the white matter in the brain. The word "leukodystrophy" comes from the Greek roots "leuko", "white", "dys", "abnormal", and "troph", "growth". The leukodystrophies are caused by imperfect growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers.

When damage occurs to white matter, immune responses can lead to inflammation in the CNS, along with loss of myelin. The degeneration of white matter can be seen in a MRI and used to diagnose leukodystrophy. Leukodystrophy is characterized by specific symptoms including decreased motor function, muscle rigidity, and eventually degeneration of sight and hearing. While the disease is fatal, the age of onset is a key factor as infants are given a lifespan of 2–8 years (sometimes longer), while adults typically live more than a decade after onset. There is a great lack of treatment, although cord blood and hematopoietic stem cell transplantation (bone marrow transplant) seem to help in certain types while further research is being done.

The combined incidence of the leukodystrophies is estimated at 1:7,600. The majority of types involve the inheritance of a recessive, dominant, or X-linked trait, while others, although involving a defective gene, are the result of spontaneous mutation rather than genetic inheritance.

Some specific symptoms vary from one type of leukodystrophy to the next but the vast majority of symptoms are shared as the causes for the disease generally have the same effects. Symptoms are dependent on the age of onset, which is predominantly in infancy and early childhood, although the exact time of onset may be difficult to determine. Hyperirritability and hypersensitivity to the environment are common, as well as some tell-tale physical signs including muscle rigidity and a backwards-bent head. Botox therapy is often used to treat patients with spasticity. Juvenile and adult onsets display similar symptoms including a decrease or loss in hearing and vision. While children do experience optic and auditory degeneration, the course of the disease is usually too rapid, causing death relatively quickly, whereas adults may live with these conditions for many years. In children, spastic activity often precedes progressive ataxia and rapid cognitive deterioration which has been described as mental retardation. Epilepsy is commonplace for patients of all ages. More progressed patients show weakness in deglutition, leading to spastic coughing fits due to inhaled saliva. Classic symptomatic progression of juvenile x-linked adrenoleukodystrophy is shown in the 1992 film, "Lorenzo's Oil".

Course and timetable are dependent on the age of onset with infants showing a lifespan of 2–8 years, juveniles 2–10 years and adults typically 10+ years. Adults typically see an extended period of stability followed by a decline to a vegetative state and death. While treatments do exist, most are in the experimental phase and can only promise a halt in the progression of symptoms, although some gene therapies have shown some symptomatic improvement. The debilitating course of the disease has led to numerous philosophical and ethical arguments over experimental clinical trials, patients’ rights and physician-assisted suicide.

Nevus anemicus is a congenital disorder characterized by macules of varying size and shape that are paler than the surrounding skin and cannot be made red by trauma, cold, or heat. The paler area is due to the blood vessels within the area which are more sensitive to the body’s normal vasoconstricting chemicals.

Ligneous conjunctivitis is a rare form of chronic conjunctivitis characterized by recurrent, fibrin-rich pseudomembranous lesions of wood-like consistency that develop mainly on the underside of the eyelid (tarsal conjunctiva). It is generally a systemic disease which may involve the periodontal tissue, the upper and lower respiratory tract, kidneys, middle ear, and female genitalia. It can be sight-threatening, and death can occasionally occur from pulmonary involvement.

It has been speculated that ligneous conjunctivitis may be a manifestation of IgG4-related disease (IgG4-RD) involving the conjunctiva.

This benign patch appears on the skin at birth or in early childhood. In most people these are under 10cm in size. If there is doubt about the diagnosis, rubbing the area causes the skin around the lesion to become red while the lesion itself does not change in color. Often the patches are difficult to see against the background color of the patient’s skin, but if sunburn develops, then the white area stands out prominently. The involved area is lighter than the normal skin, not because of a loss of pigment occurs, but because blood vessels are constricted, producing a permanent blanching of the area. This blanching is a functional rather than a structural abnormality, presumed to be caused by local increased sensitivity to catecholamines. Although the cutaneous vasculature appears normal histologically, the blood vessels within the nevus do not respond to injection of vasodilators. It has been postulated that the persistent pallor may represent a sustained localized adrenergic vasoconstriction. Results of a skin biopsy would be interpreted as normal and only physiological testing can reveal the nevus in contrast to normal skin. Stroking the patch elicits no red flare. Only the normal skin would react with a characteristic erythematous response. Examination under a Wood lamp can also reveal the nevus anemicus patch will not emphasize as a patch of vitiligo would.

Vision loss in toxic and nutritional optic neuropathy is bilateral, symmetric, painless, gradual, and progressive. Dyschromatopsia, a change in color vision, is often the first symptom. Some patients notice that certain colors, particularly red, are less bright or vivid; others have a general loss of color perception. Loss of visual acuity may start with a blur or haze at the point of fixation, followed by a progressive decline. The degree of vision loss can extend to total blindness, but a loss beyond 20/400 is rare, except in the case of methanol ingestion. Peripheral vision is usually spared since the pattern of loss typically involves a central or cecocentral scotoma, a visual field defect at or surrounding the point of fixation. This pattern can be revealed via visual field testing.

Upon examination, the pupils usually demonstrate a normal response to light and near stimulation. In those who are practically blind, the pupils will be dilated with a weak or absent response to light. The optic disc may appear normal, swollen, or hyperemic in early stages. With hyperemia, disc hemorrhages may also be present. Continued damage to the optic nerve results in the development of optic atrophy, classically seen as temporal pallor of the optic disc.

Most individuals with an uncorrected secundum ASD do not have significant symptoms through early adulthood. More than 70% develop symptoms by about 40 years of age. Symptoms are typically decreased exercise tolerance, easy fatigability, palpitations, and syncope.

Complications of an uncorrected secundum ASD include pulmonary hypertension, right-sided heart failure, atrial fibrillation or flutter, stroke, and Eisenmenger's syndrome.

While pulmonary hypertension is unusual before 20 years of age, it is seen in 50% of individuals above the age of 40. Progression to Eisenmenger's syndrome occurs in 5 to 10% of individuals late in the disease process.

Most individuals with a significant ASD are diagnosed "in utero" or in early childhood with the use of ultrasonography or auscultation of the heart sounds during physical examination.

Some individuals with an ASD have surgical correction of their ASD during childhood. The development of signs and symptoms due to an ASD are related to the size of the intracardiac shunt. Individuals with a larger shunt tend to present with symptoms at a younger age.

Adults with an uncorrected ASD present with symptoms of dyspnea on exertion (shortness of breath with minimal exercise), congestive heart failure, or cerebrovascular accident (stroke). They may be noted on routine testing to have an abnormal chest X-ray or an abnormal ECG and may have atrial fibrillation. If the ASD causes a left-to-right shunt, the pulmonary vasculature in both lungs may appear dilated on chest X-ray, due to the increase in pulmonary blood flow.