The diagnosis of PPS has been made in several ethnic groups, including Caucasian, Japanese, and sub-Saharan African. Males and females are equally likely to suffer from the syndrome. Since the disorder is very rare, its incidence rate is difficult to estimate, but is less than 1 in 10,000.

Genetic counseling for VWS involves discussion of disease transmission in the autosomal dominant manner and possibilities for penetrance and expression in offspring. Autosomal dominance means affected parents have a 50% chance of passing on their mutated "IRF6" allele to a their child. Furthermore, if a cleft patient has lip pits, he or she has a ten times greater risk of having a child with cleft lip with or without cleft palate than a cleft patient who does not have lip pits. Types of clefting between parents and affected children are significantly associated; however, different types of clefts may occur horizontally and vertically within the same pedigree. In cases where clefting is the only symptom, a complete family history must be taken to ensure the patient does not have non-syndromic clefting.

Lip pits may be surgically removed either for aesthetic reasons or discomfort due to inflammation caused by bacterial infections or chronic saliva excretion, though spontaneous shrinkage of the lip pits has occurred in some rare cases. Chronic inflammation has also been reported to cause squamous-cell carcinoma. It is essential to completely remove the entire lip pit canal, as mucoid cysts can develop if mucous glands are not removed. A possible side effect of removing the lip pits is a loose lip muscle. Other conditions associated with VWS, including CL, CP, congenital heart defects, etc. are surgically corrected or otherwise treated as they would be if they were non-syndromic.

Van der Woude syndrome (VDWS) and popliteal pterygium syndrome (PPS) are allelic variants of the same condition; that is, they are caused by different mutations of the same gene. PPS includes all the features of VDWS, plus popliteal pterygium, syngnathia, distinct toe/nail abnormality, syndactyly, and genito-urinary malformations.

Tooth and nail syndrome (also known as "Hypodontia with nail dysgenesis," and "Witkop syndrome") is a rare disorder, first described in 1965, characterized by nails that are thin, small, and friable, and which may show koilonychia at birth.

It is associated with "MSX1".

Pure hair-nail type ectodermal dysplasia is a genetic mutation in the "hair matrix and cuticle keratin KRTHB5 gene" that causes ectodermal dysplasia of hair and nail type. Manifestations of this disorder include onychodystrophy and severe hypotrichosis. It represents as an autosomal dominant trait.

In racquet nails (also known as brachyonychia, nail en raquette, and racquet thumb), the nail plate is flattened, the end of the thumb is widened and flattened, and the distal phalanx is abnormally short. In racquet nails, the width of the nail bed and nail plate is greater than their length. The condition is painless and asymptomatic.

Racquet nails usually occur on one or both thumbs, but may appear on all fingers and toes. It may be genetic, inherited as an autosomal-dominant trait, or acquired. Genetic disorders associated with racquet nail include Larsen syndrome, Brooke–Spiegler syndrome, Rubinstein–Taybi syndrome, Hajdu–Cheney syndrome, cartilage–hair hypoplasia, pycnodysostosis, acrodysostosis, and brachydactylia.

Acquired racquet nail is associated with acroosteolysis and psoriatic arthropathy. Acquired racquet nail may also be diagnostic of bone resorption in hyperparathyroidism.

Racquet nail often presents with other nail conditions such as onycholysis, koilonychia, pachyonychia, Muehrcke's lines, leuconychia, and half-and-half nails. Cosmetic surgery can be used to improve the appearance of the nails.

Onychomatricoma is a cutaneous condition characterized by a distinctive tumor of the nail matrix.

This nail disease can mimic many nail problems and should be examined and biopsied by a dermatologist. In particular, a main concern is the malignant and destructive potential that may exist.

Omphalocele has been described in two patients with Apert syndrome by Herman T.E. et al. (USA, 2010) and by Ercoli G. et al. (Argentina, 2014). An omphalocele is a birth defect in which an intestine or other abdominal organs are outside of the body of an infant because of a hole in the bellybutton area. However, the association between omphalocele and Apert syndrome is not confirmed yet, so additional studies are necessary.

Pterygium inversum unguis (also known as "Pterygium inversus unguis," and "Ventral pterygium") is characterized by the adherence of the distal portion of the nailbed to the ventral surface of the nail plate. The condition may be present at birth or acquired, and may cause pain with manipulation of small objects, typing, and close manicuring of the nail.

The syndromes associated with central polydactyly are:

Bardet–Biedl syndrome,

Meckel syndrome,

Pallister–Hall syndrome,

Legius syndrome,

Holt–Oram syndrome,

Also, central polydactyly can be associated with syndactyly and cleft hand.

Other syndromes including polydactyly include acrocallosal syndrome, basal cell nevus syndrome, Biemond syndrome, ectrodactyly-ectodermal dysplasias-cleft lip/palate syndrome, mirror hand deformity, Mohr syndrome, oral-facial-digital syndrome, Rubinstein-Taybi syndrome, short rib polydactyly, and VATER association.

It can also occur with a triphalangeal thumb.

Surgery is needed to prevent the closing of the coronal sutures from damaging brain development. In particular, surgeries for the LeFort III or monobloc midface distraction osteogenesis which detaches the midface or the entire upper face, respectively, from the rest of the skull, are performed in order to reposition them in the correct plane. These surgeries are performed by both plastic and oral and maxillofacial (OMS) surgeons, often in collaboration.

Restrictive dermopathy is a rare, lethal autosomal recessive skin condition characterized by syndromic facies, tight skin, sparse or absent eyelashes, and secondary joint changes.

Many conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier against the external environment. The skin weighs an average of four kilograms, covers an area of two square meters, and is made of three distinct layers: the epidermis, dermis, and subcutaneous tissue. The two main types of human skin are: glabrous skin, the hairless skin on the palms and soles (also referred to as the "palmoplantar" surfaces), and hair-bearing skin. Within the latter type, the hairs occur in structures called pilosebaceous units, each with hair follicle, sebaceous gland, and associated arrector pili muscle. In the embryo, the epidermis, hair, and glands form from the ectoderm, which is chemically influenced by the underlying mesoderm that forms the dermis and subcutaneous tissues.

The epidermis is the most superficial layer of skin, a squamous epithelium with several strata: the stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale. Nourishment is provided to these layers by diffusion from the dermis, since the epidermis is without direct blood supply. The epidermis contains four cell types: keratinocytes, melanocytes, Langerhans cells, and Merkel cells. Of these, keratinocytes are the major component, constituting roughly 95 percent of the epidermis. This stratified squamous epithelium is maintained by cell division within the stratum basale, in which differentiating cells slowly displace outwards through the stratum spinosum to the stratum corneum, where cells are continually shed from the surface. In normal skin, the rate of production equals the rate of loss; about two weeks are needed for a cell to migrate from the basal cell layer to the top of the granular cell layer, and an additional two weeks to cross the stratum corneum.

The dermis is the layer of skin between the epidermis and subcutaneous tissue, and comprises two sections, the papillary dermis and the reticular dermis. The superficial papillary dermis with the overlying rete ridges of the epidermis, between which the two layers interact through the basement membrane zone. Structural components of the dermis are collagen, elastic fibers, and ground substance. Within these components are the pilosebaceous units, arrector pili muscles, and the eccrine and apocrine glands. The dermis contains two vascular networks that run parallel to the skin surface—one superficial and one deep plexus—which are connected by vertical communicating vessels. The function of blood vessels within the dermis is fourfold: to supply nutrition, to regulate temperature, to modulate inflammation, and to participate in wound healing.

The subcutaneous tissue is a layer of fat between the dermis and underlying fascia. This tissue may be further divided into two components, the actual fatty layer, or panniculus adiposus, and a deeper vestigial layer of muscle, the panniculus carnosus. The main cellular component of this tissue is the adipocyte, or fat cell. The structure of this tissue is composed of septal (i.e. linear strands) and lobular compartments, which differ in microscopic appearance. Functionally, the subcutaneous fat insulates the body, absorbs trauma, and serves as a reserve energy source.

Conditions of the human integumentary system constitute a broad spectrum of diseases, also known as dermatoses, as well as many nonpathologic states (like, in certain circumstances, melanonychia and racquet nails). While only a small number of skin diseases account for most visits to the physician, thousands of skin conditions have been described. Classification of these conditions often presents many nosological challenges, since underlying etiologies and pathogenetics are often not known. Therefore, most current textbooks present a classification based on location (for example, conditions of the mucous membrane), morphology (chronic blistering conditions), etiology (skin conditions resulting from physical factors), and so on. Clinically, the diagnosis of any particular skin condition is made by gathering pertinent information regarding the presenting skin lesion(s), including the location (such as arms, head, legs), symptoms (pruritus, pain), duration (acute or chronic), arrangement (solitary, generalized, annular, linear), morphology (macules, papules, vesicles), and color (red, blue, brown, black, white, yellow). Diagnosis of many conditions often also requires a skin biopsy which yields histologic information that can be correlated with the clinical presentation and any laboratory data.

Type VII of radial polydactyly is associated with several syndromes:

Holt–Oram syndrome, Fanconi anemia (aplastic anemia by the age of 6), Townes–Brocks syndrome, and Greig cephalopolysyndactyly (also known to occur with ulnar polydactyly).

Malalignment of the nail plate is a congenital malalignment of the nail of the great toe, and is often misdiagnosed although it is a common condition.

Restrictive dermopathy (RD) is caused either by the loss of the gene ZMPSTE24, which encodes a protein responsible for the cleavage of farnesylated prelamin A into mature non-farnesylated lamin, or by a mutation in the LMNA gene. This results in the accumulation of farnesyl-prelamin A at the nuclear membrane. Mechanistically, restrictive dermopathy is somewhat similar to Hutchinson–Gilford progeria syndrome (HGPS), a disease where the last step in lamin processing is hindered by a mutation that causes the loss of the ZMPSTE24 cleavage site in the lamin A gene.

Drug-induced nail changes are caused by drug administration which may result in a large number of nail abnormalities, usually with multiple nails being affected at the same time.

Severe congenital onychogryphosis affecting all twenty nailbeds has been recorded in two families who exhibit the dominant allele for a certain gene. Congenital onychogryphosis of the fifth toe (the little toe) is fairly common, but asymptomatic and seldom brought to the attention of medical professionals. Rather, it is brought to the attention of manicurists who routinely file the clawed toenail flat.

Neoplasms of the nailbed may often present with paronychia, ingrown nail, onycholysis, pyogenic granuloma, nail-plate dystrophy, longitudinal erythronychia, bleeding, and discolorations. There are various benign and malignant neoplasms that may occur in or overlying the nail matrix and in the nailbed, and symptoms may include pain, itching, and throbbing.

Benign tumors of the nails include verruca, pyogenic granuloma, fibromas, nevus cell nevi, myxoid cysts, angiofibromas (Koenen tumors), and epidermoid cysts.

Squamous cell carcinoma of the nailbed is uncommon, and often mistaken for a pyogenic granuloma initially. Subungual melanoma is frequently diagnosed late in the course of growth.

The hallmark features of this syndrome are poorly developed fingernails, toenails, and patellae (kneecaps). Sometimes, this disease causes the affected person to have either no thumbnails or a small piece of a thumbnail on the edge of the thumb. The lack of development, or complete absence of fingernails results from the loss of function mutations in the LMX1B gene. This mutation may cause a reduction in dorsalising signals, which then results in the failure to normally develop dorsal specific structures such as nails and patellae. Other common abnormalities include elbow deformities, abnormally shaped pelvic (hip) bones, and kidney (renal) disease.

The Nail–patella syndrome is inherited via autosomal dominancy linked to aberrancy on human chromosome 9's q arm (the longer arm), 9q34. This autosomal dominancy means that only a single copy, instead of both, is sufficient for the disorder to be expressed in the offspring, meaning the chance of getting the disorder from an affected heterozygous parent is 50%. The frequency of the occurrence is 1/50,000. The disorder is linked to the ABO blood group locus.

It is associated with random mutations in the LMX1B gene. Studies have been conducted and 83 mutations of this gene have been identified.

Melanonychia is a black or brown pigmentation of the normal nail plate, and may be present as a normal finding on many digits in African-Americans, as a result of trauma, systemic disease, or medications, or as a postinflammatory event from such localized events as lichen planus or fixed drug eruption.

There are two types, longitudinal and transverse melanonychia. Longitudinal melanonychia may be a sign of subungual melanoma (acral lentiginous melanoma), although there are other diagnoses such as chronic paronychia, onychomycosis, subungual hematoma, pyogenic granuloma, glomus tumour, subungual verruca, mucous cyst, subungual fibroma, keratoacanthoma, carcinoma of the nail bed, and subungual exostosis.

The autosomal dominant form is caused by a mutation in ANKH on chromosome 5 (5p15.2-p14.1). The autosomal recessive form is caused by a mutation in a mutation in GJA1 on chromosome 6 (6q21-q22). The recessive form tends to be more severe than the dominant form.

The only treatment for this disorder is surgery to reduce the compression of cranial nerves and spinal cord. However, bone regrowth is common since the surgical procedure can be technically difficult. Genetic counseling is offered to the families of the people with this disorder.