A disorder of sex development (DSD) distinct from complete AIS (CAIS) characterized by the presence of abnormal genital development in a 46,XY individual with normal testis development and partial responsiveness to age-appropriate levels of androgens. Epidemiology There are no available data on the prevalence of PAIS in the general population. Nevertheless, resistance to androgens is the most frequent cause of XY DSD. Clinical description Patients have a highly variable genital appearance. The prototypic form of presentation is severe hypospadias, micropenis, and bifid scrotum in which the testes may or may not be descended.

Partial androgen insensitivity syndrome Other names Partial androgen resistance syndrome; Reifenstein syndrome AIS results when the function of the androgen receptor (AR) is impaired. The AR protein (pictured) mediates the effects of androgens in the human body. Specialty Endocrinology Partial androgen insensitivity syndrome ( PAIS ) is a condition that results in the partial inability of the cell to respond to androgens . [1] [2] [3] It is an X linked recessive condition. The partial unresponsiveness of the cell to the presence of androgenic hormones impairs the masculinization of male genitalia in the developing fetus, as well as the development of male secondary sexual characteristics at puberty , but does not significantly impair female genital or sexual development. [3] [4] As such, the insensitivity to androgens is clinically significant only when it occurs in individuals with a Y chromosome (or more specifically, an SRY gene ). [1] Clinical features include ambiguous genitalia at birth and primary amenhorrhoea with clitoromegaly with inguinal masses. Mullerian structures are not present in the individual. PAIS is one of three types of androgen insensitivity syndrome , which is divided into three categories that are differentiated by the degree of genital masculinization : complete androgen insensitivity syndrome (CAIS) is indicated when the external genitalia is that of a normal female, mild androgen insensitivity syndrome (MAIS) is indicated when the external genitalia is that of a normal male, and partial androgen insensitivity syndrome (PAIS) is indicated when the external genitalia is partially, but not fully masculinized. [1] [2] [5] [6] [7] [8] [9] [10] [11] Androgen insensitivity syndrome is the largest single entity that leads to 46,XY undermasculinization . [12] There are differing opinions on whether treatment is necessary.

Partial androgen insensitivity syndrome (PAIS) is a disorder of sex development that affects the growing reproductive and genital organs of a fetus. Androgen insensitivity refers to the inability of the body of an individual with a 46, XY karyotype (usually leading to normal male development) to properly respond to male sex hormones (androgens). In PAIS, the body partially responds to these hormones. Signs and symptoms of PAIS can vary greatly, causing a range of differences in genital appearance. Some individuals have severe hypospadias , an unusually small penis, and bifid scrotum . More severely affected individuals may have female external genitalia with an abnormally large clitoris, partial fusion of the labia and gynecomastia (excessive development of male breasts).

Summary Clinical characteristics. Xeroderma pigmentosum (XP) is characterized by: Sun sensitivity (severe sunburn with blistering, persistent erythema on minimal sun exposure in ~60% of affected individuals), with marked freckle-like pigmentation of the face before age two years in most affected individuals; Sunlight-induced ocular involvement (photophobia, keratitis, atrophy of the skin of the lids); Greatly increased risk of sunlight-induced cutaneous neoplasms (basal cell carcinoma, squamous cell carcinoma, melanoma). Approximately 25% of affected individuals have neurologic manifestations (acquired microcephaly, diminished or absent deep tendon stretch reflexes, progressive sensorineural hearing loss, and progressive cognitive impairment). The most common causes of death are skin cancer, neurologic degeneration, and internal cancer. The median age at death in persons with XP with neurodegeneration (29 years) was found to be younger than that in persons with XP without neurodegeneration (37 years). Diagnosis/testing. The diagnosis of XP is made on the basis of clinical findings and family history and/or by the identification of biallelic pathogenic variants in DDB2 , ERCC1 , ERCC2 , ERCC3 , ERCC4 , ERCC5 , POLH , XPA , or XPC .

A number sign (#) is used with this entry because xeroderma pigmentosum complementation group D (XPD) is caused by homozygous or compound heterozygous mutation in the excision repair gene ERCC2 (126340) on chromosome 19q13. Description Xeroderma pigmentosum is a rare autosomal recessive disorder characterized by acute photosensitivity and a predisposition to skin cancer on sun-exposed areas of the body. The primary defect in XP involves nucleotide excision repair (NER) (summary by Flejter et al., 1992). Clinical Features In a 31-year-old patient with XP classified as complementation group D by cell-fusion complementation methods, Ichihashi et al. (1988) described mild skin lesions and no apparent neurologic abnormalities despite the characteristic group D level of DNA repair deficiency. Johnson and Squires (1992) stated that more than 30 unrelated individuals with XPD were known and that less than half of them showed major abnormalities of the central nervous system, once considered to be the hallmark of XPD.

A number sign (#) is used with this entry because xeroderma pigmentosum complementation group A (XPA) is caused by homozygous or compound heterozygous mutation in the XPA gene (611153) on chromosome 9q22. Description Xeroderma pigmentosum is a genetically heterogeneous autosomal recessive disorder characterized by increased sensitivity to sunlight with the development of carcinomas at an early age. Some patients develop neurologic symptoms or a more severe clinical phenotype known as de Sanctis-Cacchione syndrome (278800) (Satokata et al., 1992). See also XPB (610651), XPC (278720), XPD (278730), XPE (278740), XPF (278760), XPG (278780), and variant XP (XPV; 278750). Clinical Features Ruder (cited by Cockayne, 1933) observed the condition in 7 out of 13 sibs.

Xeroderma pigmentosum (XP) is a rare genodermatosis characterized by extreme sensitivity to ultraviolet (UV)-induced changes in the skin and eyes, and multiple skin cancers. It is subdivided into 8 complementation groups, according to the affected gene: classical XP (XPA to XPG) and XP variant (XPV) (see these terms). Epidemiology It has an estimated prevalence of 1/1,000,000 in the USA and Europe, with higher figures in other countries (e.g. Japan, North Africa and Pakistan), particularly in communities with a high degree of consanguinity. Clinical description The severity of the clinical manifestations and the age of onset are extremely variable and are in part dependent on exposure to sunlight and the complementation group.

Xeroderma pigmentosum (XP) causes the skin and eyes to be extra sensitive to exposure to ultraviolet radiation from the sun and other sources. Symptoms begin in early childhood. People with XP can develop bad sunburns, blistering, and freckling in response to sunlight. The eyes may develop light sensitivity, corneal clouding, and swelling. Some people with XP have nervous system involvement as well. People with XP are at very high risk of developing skin cancer and other types of cancers. XP is caused by variants in one of at least nine genes involved in repairing damaged DNA.

A number sign (#) is used with this entry because xeroderma pigmentosum complementation group C (XPC) is caused by mutation in the XPC gene (613208) on chromosome 3p25. Description Xeroderma pigmentosum is a genetically heterogeneous condition characterized by increased sensitivity to ultraviolet (UV) irradiation and increased risk of skin cancer resulting from a defect in DNA repair. XPC is the most common form of XP in the white population, accounting for over a third of all cases in this group (review by Li et al., 1993). For a general discussion of xeroderma pigmentosum, see XPA (278700). Clinical Features Lynch et al. (1984) suggested that complementation group C patients may be particularly prone to malignant melanoma. Li et al. (1993) identified 2 patients with XPC confirmed by genetic analysis (613208.0003).

A number sign (#) is used with this entry because the phenotype associated with xeroderma pigmentosum complementation group B (XPB) is caused by mutation in the DNA excision repair gene ERCC3 (133510) on chromosome 2q14. Description For a general discussion of xeroderma pigmentosum, see XPA (278700), and of Cockayne syndrome, see CSA (216400). Cleaver (1990) provided a review of the causes of xeroderma pigmentosum. Clinical Features Lehmann (1982) performed cell fusion studies on cultured cells from 11 patients with Cockayne syndrome. The 11 cell lines were assigned to 3 complementation groups: 2 to group A, 8 to group B, and 1 to group C.

A number sign (#) is used with this entry because of evidence that the disorder is caused by homozygous or compound heterozygous mutation in the ERCC4 gene (133520) on chromosome 16p13. Description Xeroderma pigmentosum is an autosomal recessive disorder characterized by sun sensitivity and increased skin sensitivity to UV light, as well as an increased risk of skin cancer associated with a defect in nucleotide excision repair (NER). The XPF form of XP is usually relatively mild compared to other forms. Patients with XPF tend to have later onset of skin cancer. Some patients with XPF may develop neurologic impairment or growth defects, and are then classified as having Cockayne syndrome (summary by Kashiyama et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of xeroderma pigmentosa, see XPA (278700), and of Cockayne syndrome, see CSA (216400).

A number sign (#) is used with this entry because xeroderma pigmentosum complementation group E is caused by homozygous mutation in the DDB2 gene (600811) on chromosome 11p11. For background information on xeroderma pigmentosum, see 278700. Clinical Features Kondo et al. (1988) studied 3 Japanese patients, aged 50, 42, and 41 years, with mild XP symptoms and no neurologic abnormalities. Two had developed basal cell carcinomas at ages 46 and 41 years. Chu and Chang (1988) studied cells from 2 second-cousin patients with group E xeroderma pigmentosum who had a skin disease less severe than that seen in patients of several other complementation groups (de Weerd-Kastelein et al., 1974). Using an extension of the gel electrophoresis binding assay, Chu and Chang (1988) identified at least 1 nuclear factor that binds to DNA damaged by ultraviolet radiation or the antitumor drug cisplatin, but is notably absent in group E cells. The defect was not the result of a failure of protein transport to the nucleus since binding activity was absent in both the nuclear and cytoplasmic extracts.

Xeroderma pigmentosum Other names DeSanctis-Cacchione syndrome [1] [2] XP1 / XP2 / XP3 / XP4 / XP5 / XP6 / XP7 [3] Xeroderma pigmentosum I/II/III/IV/V/VI/VII [3] Xeroderma pigmentosum complementation group A/B/C/D/E/F/G [3] xeroderma pigmentosum group A/B/C/D/E/F/G [3] An eight-year-old girl from Guatemala with xeroderma pigmentosum [4] Specialty Medical genetics Symptoms Severe sunburn after only a few seconds in the sun, freckling in sun-exposed areas, dry skin, changes in skin pigmentation [1] Complications Skin cancer , brain cancer , cataracts [1] Usual onset Becomes visible ~6 months of age [2] Duration Lifelong Causes Genetic disorder ( autosomal recessive ) [1] Diagnostic method Based on symptoms and confirmed by genetic testing [5] Differential diagnosis Trichothiodystrophy , Cockayne syndrome , cerebrooculofacioskeletal syndrome , erythropoietic protoporphyria [6] Prevention No cure available Treatment Completely avoiding sun or UV rays, retinoid creams , vitamin D [5] [6] Prognosis Life expectancy is shortened by about 30 years. [7] Frequency • 1 in 100,000 (worldwide) [3] • 1 in 370 (India) [8] • 1 in 22,000 (Japan) [3] • 1 in 250,000 (USA) [9] • 1 in 430,000 (Europe) • 1 in 1,000,000 (UK) [3] Xeroderma pigmentosum ( XP ) is a genetic disorder in which there is a decreased ability to repair DNA damage such as that caused by ultraviolet (UV) light. [1] Symptoms may include a severe sunburn after only a few minutes in the sun, freckling in sun exposed areas, dry skin and changes in skin pigmentation. [1] Nervous system problems, such as hearing loss , poor coordination, loss of intellectual function and seizures , may also occur. [1] Complications include a high risk of skin cancer , with about half having skin cancer by age 10 without preventive efforts, and cataracts . [1] There may be a higher risk of other cancers such as brain cancers . [1] XP is autosomal recessive , with at least nine specific mutations able to result in the condition. [1] [6] Normally, the damage to DNA which occurs in skin cells from exposure to UV light is repaired by nucleotide excision repair . [1] In people with xeroderma pigmentosum, this damage is not repaired. [1] As more abnormalities form in DNA, cells malfunction and eventually become cancerous or die. [1] Diagnosis is typically suspected based on symptoms and confirmed by genetic testing . [5] There is no cure for XP. [6] Treatment involves completely avoiding the sun . [6] This includes protective clothing, sunscreen and dark sunglasses when out in the sun. [6] Retinoid creams may help decrease the risk of skin cancer. [6] Vitamin D supplementation is generally required. [5] If skin cancer occurs, it is treated in the usual way. [6] The life expectancy of those with the condition is about 30 years less than normal. [7] The disease affects about 1 in 100,000 worldwide. [3] By region, it affects about 1 in 370 in India, [8] 1 in 20,000 in Japan, 1 in 250,000 people in the United States and 1 in 430,000 in Europe. [9] It occurs equally commonly in males and females. [10] Xeroderma pigmentosum was first described in the 1870s by Moritz Kaposi . [5] [10] In 1882, Kaposi coined the term xeroderma pigmentosum for the condition, referring to its characteristic dry, pigmented skin. [10] Individuals with the disease have been referred to as "children of the night" or "moon children". [11] [12] Contents 1 Signs and symptoms 2 Genetics 2.1 XP repair proteins 3 Diagnosis 3.1 Types 4 Treatment 5 Prognosis 6 History 7 Culture 8 Research directions 9 See also 10 References 11 External links Signs and symptoms [ edit ] Child with xeroderma pigmentosum in Nepal Signs and symptoms of xeroderma pigmentosum may include: [ citation needed ] Severe sunburn when exposed to only small amounts of sunlight. These often occur during a child's first exposure to sunlight. Development of many freckles at an early age Rough-surfaced growths ( solar keratoses ), and skin cancers Eyes that are painfully sensitive to the sun and may easily become irritated, bloodshot and clouded Blistering or freckling on minimum sun exposure Telangiectasia (spider veins) Limited growth of hair on chest and legs Scaly skin Xeroderma (dry skin) Irregular dark spots on the skin Corneal ulcerations Genetics [ edit ] Xeroderma pigmentosum has an autosomal recessive pattern of inheritance. One of the most frequent defects in xeroderma pigmentosum is an autosomal recessive genetic defect in which nucleotide excision repair (NER) enzymes are mutated, leading to a reduction in or elimination of NER. [13] If left unchecked, damage caused by ultraviolet light can cause mutations in individual cell's DNA. The causes of the neurological abnormalities are poorly understood and are not connected with exposure to ultraviolet light. The most current theories suggest that oxidative DNA damage is generated during normal metabolism in the central nervous system, and that some types of this damage must be repaired by NER. [14] Since DNA repair is under genetic control, it can mutate.

Poikiloderma vasculare atrophicans Other names Parapsoriasis variegata [1] or Parapsoriasis lichenoides [2] Typical skin changes and discoloration described as poikiloderma vasculare atrophicans Specialty Dermatology Poikiloderma vasculare atrophicans ( PVA ), is a cutaneous condition ( skin disease ) characterized by hypo- or hyperpigmentation (diminished or heightened skin pigmentation , respectively), telangiectasia and skin atrophy . [3] [4] [5] Other names for the condition include prereticulotic poikiloderma and atrophic parapsoriasis . [6] The condition was first described by pioneer American pediatrician Abraham Jacobi in 1906. [7] PVA causes areas of affected skin to appear speckled red and inflamed, yellowish and/or brown, gray or grayish-black, with scaling and a thinness that may be described as "cigarette paper". [3] On the surface of the skin, these areas may range in size from small patches, to plaques (larger, raised areas), to neoplasms (spreading, tumor-like growths on the skin). [3] [6] Mycosis fungoides, a type of skin lymphoma , may be a cause of PVA. The condition may also be caused by, associated with or accompany any of the following conditions or disorders: other skin lymphomas, dermatomyositis , lupus erythematosus , Rothmund–Thomson syndrome , Kindler syndrome , dyskeratosis congenita , and chronic radiodermatitis . [4] Rare causes include arsenic ingestion, and the condition can also be idiopathic . [1] [3] [5] PVA may be considered a rare variant of cutaneous T-cell lymphoma , a non-Hodgkin's form of lymphoma affecting the skin. [7] It may also be included among a number of similar conditions that are considered as precursors to mycosis fungoides . PVA is believed to be a syndrome closely associated with large-plaque parapsoriasis and its cohort retiform parapsoriasis ; including PVA, all three conditions fit within an updated view of the once ambiguous classification scheme known as parapsoriasis . [5] Contents 1 Presentation 2 Cause 3 Diagnosis 3.1 Classification 4 Management 5 See also 6 References 7 External links Presentation [ edit ] The layers of the epidermis (left). Melanocytes (rlght), located in the bottom epidermal layer, produce melanin. PVA can be characterized by speckled, combined hyper- and hypopigmentation in the plaques or patches of affected skin. [5] Hyperpigmentation is excess coloration, or darkening of the skin, [8] while hypopigmentation is a diminished or pallid coloring to the skin.

Familial supernumerary nipples is a rare breast malformation characterized by the presence, in various members of a single family, of one or more nipple(s) and/or their related tissue, in addition to the normal bilateral chest nipples. The anomaly is usually situated along the embryonic milk line, from axillae to inguinal regions, but other locations are also possible. Association with dental abnormalities, Becker nevus, renal or underlying breast tissue malignancy and genitourinary malformations has been reported.

Supernumerary nipple Other names Third nipple , Triple nipple , Accessory nipple , [1] Polythelia Specialty Medical genetics , dermatology A supernumerary nipple is an additional nipple occurring in mammals , including humans . They are often mistaken for moles . Studies variously report the prevalence of supernumerary nipples as approximately 1 in 18 and 1 in 40. [2] [3] [1] The nipples appear along the two vertical " milk lines ", which start in the armpit on each side, run down through the typical nipples and end at the groin. They are classified into eight levels of completeness from a simple patch of hair to a milk-bearing breast in miniature. [4] [5] Contents 1 Types 2 Clinical significance 2.1 Clinical presentation 2.2 Associations 2.3 Treatment and prognosis 3 Society and culture 3.1 Television 4 See also 5 References 6 External links Types [ edit ] Type Glandular tissue Nipple Areola Fat tissue Hair patch 1 yes yes yes yes 2 yes yes 3 yes yes 4 yes 5 ("pseudomamma") yes yes yes 6 ("polythelia") yes 7 ("polythelia areolaris") yes 8 ("polythelia pilosa") yes [6] Polythelia refers to the presence of an additional nipple alone while polymastia denotes the much rarer presence of additional mammary glands . Although usually presenting on the milk line, pseudomamma can appear as far away as the foot. [7] A possible relationship with mitral valve prolapse has been proposed. [8] Clinical significance [ edit ] Clinical presentation [ edit ] May remain undetected. Occasionally, the supernumerary nipple is noticed when hormonal changes during adolescence, menstruation, or pregnancy cause increased pigmentation, fluctuating swelling, tenderness, or even lactation.

Metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia.[2] The condition gets its name from the distinctive sweet odor of affected infants' urine Maple syrup urine disease Other names Branched-chain ketoaciduria Isoleucine (pictured above), leucine , and valine are the branched-chain amino acids that build up in MSUD. Specialty Medical genetics Maple syrup urine disease ( MSUD ) is an autosomal recessive [1] metabolic disorder affecting branched-chain amino acids . It is one type of organic acidemia . [2] The condition gets its name from the distinctive sweet odor of affected infants' urine, particularly prior to diagnosis and during times of acute illness. [3] Contents 1 Classification 2 Signs and symptoms 2.1 Classic MSUD 2.2 Intermediate MSUD 2.3 Intermittent MSUD 2.4 Thiamine-response MSUD 2.5 Later onset 3 Causes 4 Pathophysiology 5 Diagnosis 6 Prevention 7 Treatment 7.1 Monitoring 7.2 Diet control 7.3 Liver transplantation 7.4 Pregnancy 8 Prognosis 9 Epidemiology 10 Research directions 10.1 Gene therapy 10.2 Phenylbutyrate therapy 11 See also 12 References 13 External links Classification [ edit ] Maple syrup urine disease can be classified by its pattern of signs and symptoms, or by its genetic cause. The most common and severe form of this disease is the classic type, which appears soon after birth, and as long as it remains untreated, gives rise to progressive and unremitting symptoms. Variant forms of the disorder may become apparent only later in infancy or childhood, with typically less severe symptoms that may only appear during times of fasting, stress or illness, but still involve mental and physical problems if left untreated.

A number sign (#) is used with this entry because of evidence that a mild variant of maple syrup urine disease (MSUDMV) is caused by homozygous mutation in the PPM1K gene (611065) on chromosome 4q22. One such family has been reported. Description The mild variant of MSUD is characterized by increased plasma levels of branched-chain amino acids (BCAA) apparent at birth. Treatment with a low-protein diet free of BCAA can result in normal psychomotor development and lack of metabolic episodes; however, plasma levels of BCAA may remain elevated (summary by Oyarzabal et al., 2013). For a general description and a discussion of genetic heterogeneity of maple syrup urine disease, see 248600. Clinical Features Oyarzabal et al. (2013) reported a 21-year-old woman with a mild variant of maple syrup urine disease.

A rare inherited disorder of branched-chain amino acid metabolism classically characterized by poor feeding, lethargy, vomiting and a maple syrup odor in the cerumen (and later in urine) noted soon after birth, followed by progressive encephalopathy and central respiratory failure if untreated. The four overlapping phenotypic subtypes are: classic, intermediate, intermittent and thiamine-responsive MSUD. Epidemiology The estimated prevalence is around 1/150,000 live births, from published and unpublished newborn screening data. Clinical description Classic MSUD presents in the first days of life with poor feeding and drowsiness followed by a worsening encephalopathy with lethargy, intermittent apnea, stereotypic movements ("fencing" and ''bicycling") and opisthotonus. Coma and central respiratory failure supervene 7 to 10 days after birth.

Maple syrup urine disease (MSUD) occurs when the body is unable to breakdown certain parts of proteins. This leads to the build-up of toxic substances that can cause organ and brain damage. There are several forms of MSUD. The most common is the classic or infantile form. Symptoms of the classic form of MSUD start in early infancy and include poor feeding, irritability, extra sleepiness, and muscle spasms. If untreated, respiratory failure (lack of oxygen getting to the blood) may occur.

Kidney stones (also called renal stones or urinary stones) are small, hard deposits that form in one or both kidneys; the stones are made up of minerals or other compounds found in urine. Kidney stones vary in size, shape, and color. To be cleared from the body (or "passed"), the stones need to travel through ducts that carry urine from the kidneys to the bladder (ureters) and be excreted. Depending on their size, kidney stones generally take days to weeks to pass out of the body. Kidney stones can cause abdominal or back pain (known as renal colic). Renal colic usually begins sporadically but then becomes constant and can lead to nausea and vomiting.

A number sign (#) is used with this entry because of evidence that dermatopathia pigmentosa reticularis (DPR) is caused by heterozygous mutation in the keratin-14 gene (KRT14; 148066) on chromosome 17q21. One such family has been reported. A closely related disorder, Naegeli-Franceschetti-Jadassohn syndrome (NFJS; 161000), is also caused by heterozygous mutation in the KRT14 gene. Description Dermatopathia pigmentosa reticularis is a rare heritable disorder consisting of a triad of cutaneous findings including reticulate hyperpigmentation, noncicatricial alopecia, and onychodystrophy. Variable features include adermatoglyphia, hypohidrosis or hyperhidrosis, and palmoplantar hyperkeratosis (Heimer et al., 1992). Clinical Features Heimer et al. (1992) described a family with 9 cases of dermatopathia pigmentosa reticularis distributed through 6 sibships of 4 generations.

A rare, genetic, ectodermal dysplasia characterized by a widespread, early-onset, reticulate hyperpigmentation that persists throughout life, mild, diffuse non-cicatricial alopecia, and onychodystrophy. There are no dental anomalies. Patients may also present with adermatoglyphia, palmoplantar hyperkeratosis, acral dorsal blistering, and hypohidrosis or hyperhidrosis.

Dermatopathia pigmentosa reticularis Other names Dermatopathic pigmentosa reticularis [1] : 511 Dermatopathia pigmentosa reticularis has an autosomal dominant pattern of inheritance Specialty Medical genetics Dermatopathia pigmentosa reticularis is a rare, autosomal dominant [2] congenital disorder that is a form of ectodermal dysplasia . Dermatopathia pigmentosa reticularis is composed of the triad of generalized reticulate hyperpigmentation , noncicatricial alopecia , and onychodystrophy . [3] : 856 Contents 1 Presentation 2 Cause 3 Treatment 4 See also 5 References 6 External links Presentation [ edit ] Symptoms include lack of sweat glands, thin hair, brittle nails, mottled skin, and lack of fingerprints. [4] DPR is very similar to the related Naegeli-Franceschetti-Jadassohn syndrome . Both cause an affected person to lack fingerprints, have a lace-like pattern of hyperpigmentation and hyperkeratosis of the palms of the hands and soles of the feet. DPR is distinguished from NFJS by the duration of hyperpigmentation and lack of dental abnormalities. [5] Cause [ edit ] DPR is caused by a mutation in the keratin 14 gene. [6] Treatment [ edit ] This section is empty. You can help by adding to it . ( April 2017 ) See also [ edit ] List of cutaneous conditions caused by mutations in keratins References [ edit ] ^ Freedberg, et al. (2003).