Approximately 100 cases have been described in the literature to date.

The facial features are characteristic and include

- Deep set eyes

- Strabismus

- Myopia

- Marked nasal root

- Broad and/or beaked nasal bridge

- Prominent Cupid's bow

- Everted lower lip

- Tented upper lip

- Large mouth

- Widely spaced teeth

- Wide and shallow palate

- Ears with thick and overfolded helix

Most have a smiling appearance.

Intellectual disability is severe. Language is absent or limited to only a few words. Stereotypic movements particularly of the arms, wrists and fingers is almost universal. Hypotonia is common (75%) as is an unsteady gait. All have delayed walking. Other features include a single (simian) palmar crease, long, slender fingers, flat feet and cryptorchidism (in males). Finger clubbing and the presence of fetal pads is common. Hyperventilation occurs in over half and is frequently followed by apnea and cyanosis. During these episodes aerophagia may occur. Constipation is common. Microcephaly and seizures may occur. Hypopigmented skin macules have occasionally been reported.

The symptoms associated with the disorder are often confused for other dermatological disorders. The symptoms below are ones specifically associated with IPS.

Bart–Pumphrey syndrome (also known as "Palmoplantar keratoderma with knuckle pads and leukonychia and deafness") is a cutaneous condition characterized by hyperkeratoses (knuckle pads) over the metacarpophalangeal, proximal and distal interphalangeal joints.

It was characterized in 1967.

It can be associated with GJB2.

Pregnancies that have a foetus affected with this syndrome are complicated because of polyhydramnion. Complications arise because of opaque amnionic fluid resulting from the shedding of skin. As a result, ultrasounds are difficult to conduct. Triggered by the harsh environment in the uterus, delivery results around 30– 34 weeks of gestation (pregnancy) and the baby is born in prematurely.

The differential diagnosis is quite extensive and includes

- Buschke–Fischer–Brauer disease

- Curth–Macklin ichthyosis

- Gamborg Nielsen syndrome

- Greither disease

- Haber syndrome

- Hereditary punctate palmoplantar keratoderma

- Jadassohn–Lewandowsky syndrome

- Keratosis follicularis spinulosa decalvans

- Keratosis linearis with ichthyosis congenital and sclerosing keratoderma syndrome

- Meleda disease

- Mucosa hyperkeratosis syndrome

- Naegeli–Franceschetti–Jadassohn syndrome

- Naxos disease

- Olmsted syndrome

- Palmoplantar keratoderma and leukokeratosis anogenitalis

- Pandysautonomia

- Papillomatosis of Gougerot and Carteaud

- Papillon–Lefèvre syndrome

- Punctate porokeratotic keratoderma

- Richner–Hanhart syndrome

- Schöpf–Schulz–Passarge syndrome

- Unna Thost disease

- Vohwinkel syndrome

- Wong's dermatomyositis

In terms of the signs/symptoms of rhizomelic chondrodysplasia punctate one finds the following to be consistent with such a condition:

- Bilateral shortening of the femur

- Post-natal growth problems (deficiency)

- Cataracts

- Intellectual disability is present

- Possible seizures

- Possible infections of respiratory tract

Howel–Evans syndrome is an extremely rare condition involving thickening of the skin in the palms of the hands and the soles of the feet (hyperkeratosis). This familial disease is associated with a high lifetime risk of esophageal cancer. For this reason, it is sometimes known as tylosis with oesophageal cancer (TOC).

The condition is inherited in an autosomal dominant manner, and it has been linked to a mutation in the "RHBDF2" gene. It was first described in 1958.

Pitt–Hopkins syndrome is a rare genetic disorder characterized by developmental delay, a wide mouth, distinctive facial features, and intermittent hyperventilation followed by apnea. It is associated with an abnormality within chromosome 18: specifically, it is caused by an insufficient expression of the TCF4 gene.

The symptoms can occur anywhere between days to months after administration of the offending medication, depending on the dose and speed of administration (Baack and Burgdorf, 1991; Demirçay, 1997). The patient first experiences tingling and/or numbness of the palms and soles that evolves into painful, symmetric, and well-demarcated swelling and red plaques. This is followed by peeling of the skin and resolution of the symptoms (Apisarnthanarax and Duvic 2003).

Rhizomelic chondrodysplasia punctata is a rare, developmental brain disorder characterized by systemic shortening of the proximal bones (i.e. rhizomelia), seizures, recurrent respiratory tract infections, and congenital cataracts. The affected individuals have low levels of plasmalogens.

Meleda disease (MDM) or "mal de Meleda", also called Mljet disease, keratosis palmoplantaris and transgradiens of Siemens, (also known as "Acral keratoderma," "Mutilating palmoplantar keratoderma of the Gamborg-Nielsen type," "Palmoplantar ectodermal dysplasia type VIII", and "Palmoplantar keratoderma of the Norrbotten type") is an extremely rare autosomal recessive congenital skin disorder in which dry, thick patches of skin develop on the soles of the hands and feet, a condition known as palmoplantar hyperkeratosis.

Chemotherapy-induced acral erythema (also known as palmar-plantar erythrodysesthesia, palmoplantar erythrodysesthesia, or hand-foot syndrome) is reddening, swelling, numbness and desquamation (skin sloughing or peeling) on palms of the hands and soles of the feet (and, occasionally, on the knees, elbows, and elsewhere) that can occur after chemotherapy in patients with cancer. Hand-foot syndrome is also rarely seen in sickle-cell disease. These skin changes usually are well demarcated. Acral erythema typically disappears within a few weeks after discontinuation of the offending drug.

Keratolytic Winter erythema ( Oudtshoorn disease and Oudtshoorn skin, }is a rare autosomal dominant skin disease of unknown cause which causes redness and peeling of the skin on the palms and soles. Onset, increased prominence and severity usually occurs during winter. It is a type of genodermatosis.

The name "Oudtshoorn skin" derives from the town of Oudtshoorn in the Western Cape province of South Africa, where the disorder was first described. It is one of several genetic disorders known to be highly prevalent among the Afrikaner population.

KWE is characterized by a number of anomalies affecting the skin. Erythema causes redness of the skin, which is generally associated with inflammation and irritation. Including erythema and hyperkeratosis (thickening of the stratum corneum), naturally occurring keratolytic peeling and scaling, with increased manifestation in winter, are prevailing features of the disorder.

Erythema in KWE has been attributed to necrobiosis (cellular death) within the malpighian layer (the innermost layer of the epidermis). Peeling and scaling are caused by spreading dissection of the stratum corneum, correlating to the underlying necrobiosis.

The effects of KWE appear intermittently as patches on the skin of the palms and soles, with these patches appearing on the limbs, buttocks and torso in severe cases. Facial lesions of this type have also been reported with the disorder, though this is considered to be an extremely rare occurrence.

Onset and cyclical recurrence of KWE have shown to be associated with the arrival of winter, or winter-like weather. Worsening of symptoms during this time may be considered as an indicator of recurrent onset in patients known to have the disorder, and age of initial onset can be from early childhood to young adulthood, with attenuation of symptoms sometimes happening after age 30. Patients first exhibiting the disorder at a younger age may also experience worsened symptoms. Currently, no specific correlating factor or reason for winter-related manifestation has been established, though the coldness and dryer air common to winter conditions may be suspect. Winter onset is, however, considered to be a distinguishing feature of KWE among other erythematic skin disorders.

When peeling of skin occurs, the newly exposed layer of skin underneath is moist, raw and very sensitive. While this may result in minor discomfort and inconvenience, in severe cases of KWE where large areas of raw skin are present, it is often life-altering and debilitating.

KWE is inherited in an autosomal dominant manner. This means that the defective gene responsible for the disorder is located on an autosome (chromosome 8 is an autosome), and one copy of the defective gene is sufficient to cause the disorder when inherited from a parent who also has the disorder.

KWE can begin as a spontaneous mutation, first appearing in an individual with no previous family history of the disorder. This may be due to a genetic predisposition for the disorder, possibly connected to the Oudtshoorn ancestral line.

Clinically, three distinct patterns of palmoplantar keratoderma may be identified: diffuse, focal, and punctate.

Diffuse palmoplantar keratoderma is a type of palmoplantar keratoderma that is characterized by an even, thick, symmetric hyperkeratosis over the whole of the palm and sole, usually evident at birth or in the first few months of life. Restated, diffuse palmoplantar keratoderma is an autosomal dominant disorder in which hyperkeratosis is confined to the palms and soles. The two major types can have a similar clinical appearance:

- "Diffuse epidermolytic palmoplantar keratoderma" (also known as "Palmoplantar keratoderma cum degeneratione granulosa Vörner," "Vörner's epidermolytic palmoplantar keratoderma", and "Vörner keratoderma") is one of the most common patterns of palmoplantar keratoderma, an autosomal dominant condition that presents within the first few months of life, characterized by a well-demarcated, symmetric thickening of palms and soles, often with a "dirty" snakeskin appearance due to underlying epidermolysis.

- "Diffuse nonepidermolytic palmoplantar keratoderma" (also known as "Diffuse orthohyperkeratotic keratoderma," "Hereditary palmoplantar keratoderma," "Keratosis extremitatum progrediens," "Keratosis palmoplantaris diffusa circumscripta," "Tylosis," "Unna–Thost disease", and "Unna–Thost keratoderma") is inherited as an autosomal dominant condition and is present from infancy, characterized by a well-demarcated, symmetric, often "waxy" keratoderma involving the whole of the palms and soles.

Melkersson–Rosenthal syndrome (also termed "Miescher-Melkersson-Rosenthal syndrome"), is a rare neurological disorder characterized by recurring facial paralysis, swelling of the face and lips (usually the upper lip - cheilitis granulomatosis) and the development of folds and furrows in the tongue (fissured tongue). Onset is in childhood or early adolescence. After recurrent attacks (ranging from days to years in between), swelling may persist and increase, eventually becoming permanent. The lip may become hard, cracked, and fissured with a reddish-brown discoloration. The cause of Melkersson–Rosenthal syndrome is unknown, but there may be a genetic predisposition. It has been noted to be especially prevalent among certain ethnic groups in Bolivia. It can be symptomatic of Crohn's disease or sarcoidosis. Approximately 400 cases have been reported worldwide.

Individuals with acrodermatitis enteropathica may present with the following:

- Blistering of skin

- Dry skin

- Emotional lability

- Glossitis

- Pustule

Alopecia (loss of hair from the scalp, eyebrows, and eyelashes) may occur. Skin lesions may be secondarily infected by bacteria such as "Staphylococcus aureus" or fungi such as "Candida albicans". These skin lesions are accompanied by diarrhea.

Melkersson–Rosenthal syndrome may recur intermittently after its first appearance. It can become a chronic disorder. Follow-up care should exclude the development of Crohn's disease or sarcoidosis.

MDM is most common on the Dalmatian island of Mljet (or "Meleda"), thought to be because of a founder effect. It is of autosomal recessive inheritance. It may be caused by a mutation on the "SLURP1" gene, located on chromosome 8.

Acrokeratosis verruciformis (also known as "Acrokeratosis verruciformis of Hopf" is a rare autosomal dominant disorder appearing at birth or in early childhood, characterized by skin lesions that are small, verrucous, flat papules resembling warts along with palmoplantar punctate keratoses and pits. However sporadic forms, whose less than 10 cases have been reported, presents at a later age, usually after the first decade and generally lack palmoplantar keratoses.

Whether acrokeratosis verruciformis and Darier disease are related or distinct entities has been controversial, like Darier's disease, it is associated with defects in the ATP2A2 gene. however the specific mutations found in the ATP2A2 gene in acrokeratosis verruciformis have never been found in Darier's disease.

Peeling skin syndrome (also known as "Acral peeling skin syndrome," "Continual peeling skin syndrome," "Familial continual skin peeling," "Idiopathic deciduous skin," and "Keratolysis exfoliativa congenita") is an autosomal recessive disorder characterized by lifelong peeling of the stratum corneum, and may be associated with pruritus, short stature, and easily removed anagen hair.

The acral form can be associated with "TGM5".

Fissured tongue is seen in Melkersson-Rosenthal syndrome (along with facial nerve paralysis and granulomatous cheilitis). It is also seen in most patients with Down syndrome, in association with geographic tongue, in patients with oral manifestations of psoriasis, and in healthy individuals. Fissured tongue is also sometimes a feature of Cowden's syndrome.

The clinical appearance is considerably varied in both the orientation, number, depth and length of the fissure pattern. There are usually multiple grooves/furrows 2–6 mm in depth present. Sometimes there is a large central furrow, with smaller fissures branching perpendicularly. Other patterns may show a mostly dorsolateral position of the fissures (i.e. sideways running grooves on the tongue's upper surface). Some patients may experience burning or soreness.

Symptoms include severe seborrheic dermatitis of the scalp, severe diarrhea, recurrent local and systemic infection, central nervous system problems, and failure to thrive. Other symptoms also include scaling on the trunk and limbs, red patches of skin on parts of the body that bend, fevers, reduced blood protein levels, thick red skin patches, peeling of the skin, itching, corneal ulcers. wasting of the lymph nodes, underdeveloped lymphatics, anemia, wasting, and nervous system deficiency. The disease may then spread to the rest of the epidermis with the appearance of crusty, dry, moist or greasy scaling on the scalp. Scaling could also appear behind the ears, nose or eyebrows, or around the mouth; peeling of the skin may also happen in these areas. If left untreated, the skin infections will cause loss of protein or electrolytes. Leiner’s Disease may also be accompanied by a systemic reaction that is most evident in its gastrointestinal manifestation.

It is caused by a deficit of the complement protein, C5; however, case reports have described it in relation to deficits in either C3 or C4.