Integumentary System - Abnormalities

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Structural developmental anomalies of the skin - Developmental hamartomata of the epidermis and epidermal appendages | Developmental anomalies of skin pigmentation | KC24 Neonatal nutritional disorders affecting the skin | Hamartomata derived from dermal connective tissue | Skin disorders associated with prematurity | Developmental defects of hair or nails | Developmental anomalies of cutaneous vasculature | Congenital anomalies of skin development

Disorders involving the integument of foetus or newborn - KC20 Conditions involving the umbilical cord | KC21 Inflammatory dermatoses of the newborn | KC22 Neonatal disorders of subcutaneous fat | KC23 Neonatal disorders of the oral mucosa


This page introduces abnormalities associated with the integumentary system and its specializations. Note that each related page will also contain specific information for that component of this system.

Diseases of the skin incorporate conditions affecting the epidermis, its appendages (hair, hair follicle, sebaceous glands, apocrine sweat gland apparatus, eccrine sweat gland apparatus and nails) and associated mucous membranes (conjunctival, oral and genital), the dermis, the cutaneous vasculature and the subcutaneous tissue (subcutis). (ICD-11)

Integumentary Links: integumentary | Lecture | hair | tooth | nail | integumentary gland | mammary gland | vernix caseosa | melanocyte | touch | Eyelid | outer ear | Histology | integumentary abnormalities | Category:Integumentary
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Some Recent Findings

  • A novel homozygous deletion in EXPH5 causes a skin fragility phenotype[1] "Epidermolysis bullosa simplex (EBS) is the most common form of EB. Eight different genes have been implicated in the pathogenesis of different types of EBS, but a substantial portion of the cases cannot be attributed to mutations in known genes. Recently, recessive mutations in the gene EXPH5 (encoding exophilin-5, also known as Slac2-b) were identified in patients affected with a mild form of EBS. We used immunohistochemistry, Sanger sequencing and PCR-restriction fragment length polymorphism analysis to identify the cause of mild congenital skin fragility in a 3-year-old girl. No mutations were detected in KRT5 or KRT14, but we identified a novel homozygous deletion in EXPH5, which was found to cosegregate with the disease phenotype in the family."
  • Comparison between human fetal and adult skin[2]
More recent papers  
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Search term: Integumentary congenital abnormalities | Aplasia cutis congenita

Congenital anomalies of skin development

Cutis Aplasia
(Image: NZ Crown copyright)

Congenital anomalies of skin development

LC60 Aplasia cutis congenita - Congenital absence of skin. The commonest form presents as a defect limited to the scalp. It is also a component of a number of genetic syndromes.

Congenital absence of the skin, particularly on the scalp, larger defects may extend to the dura or meninges. Generally isolated lesions, but can also be associated with a variety of other genetic disorders. Heals as a flat scar or keloid lump.

OMIM Database Search: "Cutis Aplasia"

Developmental hamartomata of the epidermis and epidermal appendages

LC01 Pilosebaceous hamartoma | LC02 Complex epidermal hamartoma

LC00 Keratinocytic epidermal hamartoma

LC00 Keratinocytic epidermal hamartoma - Keratinocytic epidermal hamartoma or epidermal naevus is a congenital hamartomatous epidermal malformation composed of keratinocytes. It is thought to arise as a result of somatic mutation: early embryonic mutations can give rise to extensive systematised naevi, though typically epidermal naevi are localized linear papillomatous or verrucous plaques. Histologically they exhibit acanthosis, papillomatosis and acanthosis.

LC01 Pilosebaceous hamartoma

LC01 Pilosebaceous hamartoma - Hamartomatous malformation involving elements originating from the developing pilosebaceous follicle.

LC02 Complex epidermal hamartoma

LC02 Complex epidermal hamartoma - Hamartomatous malformation composed of elements deriving from several components of the developing epidermis and epidermal appendages.

Developmental anomalies of skin pigmentation

2F20.2 Congenital melanocytic naevus

LC10 Dermal melanocytosis

LC10 Dermal melanocytosis - The presence at birth of functional melanocytes within the dermis. Most commonly this is as a result of incomplete migration of melanocytes to the epidermis as in lumbosacral dermal melanocytosis (Mongolian spot). Less commonly it is due to circumscribed hamartomatous proliferation of melanocytes in the dermis (e.g. Naevus of Ota).

2F20.2 Congenital melanocytic naevus

2F20.2 Congenital melanocytic naevus - Congenital melanocytic naevi are circumscribed areas of skin pigmentation present at birth as a result of abnormal intrauterine proliferation of melanocytes within the dermis, the epidermis or both. They may range in size from a few millimetres to many centimetres in diameter. If their projected or final adult maximal diameter is greater than 20 cm they are termed giant congenital melanocytic naevi.

Neonatal nutritional disorders affecting the skin

KC24 Neonatal nutritional disorders affecting the skin

LC20 Connective tissue hamartoma

Hamartomata derived from dermal connective tissue

Hamartomata derived from dermal connective tissue

Skin disorders associated with prematurity

Skin disorders associated with prematurity

Developmental defects of hair or nails

Developmental defects of hair or nails

LC30 Developmental defects of hair or hair growth

LC31 Developmental defects of the nail apparatus

Developmental anomalies of cutaneous vasculature

Developmental anomalies of cutaneous vasculature

LC50 Developmental capillary vascular malformations of the skin

LC50 Developmental capillary vascular malformations of the skin

LC50.0 Salmon patch - A common skin condition of neonates, characterized by flat, deep-pink localized areas of capillary dilation that occur predominantly on the back of the neck, lower occiput, upper eyelids, upper lip, and bridge of the nose. The areas disappear permanently by about 2 years of age.

LC50.1 Port-wine stain - A port-wine stain is defined as a macular telangiectatic area of skin which is present at birth and does not spontaneously involute. Port-wine stains may be localized or extensive and they are often associated with an underlying disorder.

LC51 Developmental venous malformations involving the skin

LC51 Developmental venous malformations involving the skin

LC52 Complex or combined developmental vascular malformations involving the skin

LC52 Complex or combined developmental vascular malformations involving the skin

LD26.60 Angio-osteohypertrophic syndrome - Angio-osteohypertrophic (AOH) syndrome is a congenital vascular bone syndrome characterized by the presence of vascular malformations in a limb resulting in limb overgrowth. Depending on whether the malformations are slow flow venous or fast flow arteriovenous the syndrome may be divided into two subtypes, Klippel-Trénaunay and Parkes-Weber syndromes respectively. Some cases of the latter are associated with mutations in the RASA1 gene.

LD28.1 Ehlers-Danlos Syndrome

LD28.1 Ehlers-Danlos syndrome - is a heterogeneous group of inherited disorders of connective tissue, principally collagen, that range in severity from mild joint hypermobility to life-threatening fragility of soft tissue and vasculature.

The main features of classic Ehlers-Danlos syndrome (EZDS), which includes EDS I and EDS II, are loose-jointedness and fragile, bruisable skin that heals with peculiar scars. The syndrome is caused by mutation in the collagen gene. Infants are born prematurely due to premature rupture of fetal membranes.

Links: "Search OMIM" | GeneReviews | Ehlers-Danlos Syndrome, Vascular Type | Ehlers-Danlos Syndrome, Kyphoscoliotic Form

EC30 Epidermolysis Bullosa Simplex

EC30 Epidermolysis bullosa simplex

File:Epidermolysis bullosa simplex histology[3]

An autosomal dominant disease of keratin, generating skin fagility and non-scarring blisters of the skin caused by little or no trauma.

Four clinical subtypes:

  1. EBS - Weber-Cockayne - mild blistering of the hands and feet
  2. EBS - Koebner
  3. EBS - mottled pigmentation
  4. EBS - Dowling-Meara - generalized blistering which can be fatal.

Links: Search OMIM | GeneReviews

EC20.02 Autosomal Recessive Congenital Ichthyosis

EC20.02 Autosomal recessive congenital ichthyosis

Ichthyosis is an excessive keratinization disorder.

Links: Search OMIM | GeneReviews

Congenital absence of the skin, particularly on the scalp, larger defects may extend to the dura or meninges. Generally isolated lesions, but can also be associated with a variety of other genetic disorders. Heals as a flat scar or keloid lump.

LD27.00 Incontinentia Pigmenti

LD27.00 Incontinentia pigmenti - Incontinentia pigmenti is an X-linked dominant gene disorder due to abnormalities of the NF-kappa-B (NEMO) gene on chromosome Xq28. It is lethal in male fetuses but the presence of a normal second X chromosome in females results in a mosaicism which is compatible with life. Affected females present in infancy with skin blisters in linear arrays (Blaschko lines) typically on the scalp and limbs. Within the first few months of life these are succeeded by warty changes and hyperpigmentation. These tend to resolve over time, often leaving atrophic streaks. Associated features include abnormal dentition, ocular defects and a variety of neurological complications.

"An X-linked dominant disorder with most but not all cases affecting females. The skin changes follow characteristic four stages. In the neonatal period the first stage is noted with blisters often preceded or accompanied by erythema. These involve any part of the body but usually not the face. They do not cross the midline. These lesions are best seen in the second photograph in the groin and suprapubic region. The lesions follow a linear distribution in the limbs and circumferentially around the trunk. Crops of lesions may occur over a period of weeks to few months. During that stage, peripheral eosinophilia may be noted. The second stage follows and is characterised by hyperkeratosis or verrucous changes. At times the 2 stages occur simultaneously as noted in the first and third photograph. The third stage is that of hyperpigmentation typically appearing as streaks or whorls. It may be present throughout childhood. The fourth stage seen in teenage or adults is that of pale or atrophic streaks. In the neonatal period, IP must be differentiated from herpetic lesions, bullous impetigo and epidermolysis bullosa." (Text and Images: NZ Crown copyright)

Links: Search OMIM

EC20 Genetic disorders of keratinisation

EC20 Genetic disorders of keratinisation

EC20.0 Non-syndromic ichthyosis - EC20.00 Ichthyosis vulgaris| EC20.01 X-linked ichthyosis | EC20.02 Autosomal recessive congenital ichthyosis | EC20.03 Keratinopathic ichthyoses

EC20.00 Ichthyosis vulgaris - Ichthyosis vulgaris accounts for 95% of all cases of hereditary ichthyosis. It is an autosomal dominant condition due to filaggrin gene mutations. At birth the skin may appear normal but it gradually becomes dry, rough and scaly, with most signs and symptoms appearing by the age of 5. Ichthyosis vulgaris can affect all parts of the skin surface including the face and scalp though the limb flexures are usually spared. Hyperlinearity of the palms is a characteristic feature. It is closely associated with the development of atopic eczema.

EC20.1 Hereditary skin peeling

EC20.2 Hereditary acantholytic dermatoses

EC20.3 Hereditary palmoplantar keratodermas - EC20.30 Diffuse palmoplantar keratodermas | EC20.31 Focal palmoplantar keratodermas | EC20.32 Papular palmoplantar keratodermas

Harlequin Ichthyosis

EC20.02 Autosomal recessive congenital ichthyosis - A heterogeneous group of genetically-determined ichthyoses with autosomal recessive inheritance.

Severe recessive congenital skin disease where infants develop large, armor-like skin plates separated by deep fissures. Caused by mutations in the gene encoding ATP-Binding Cassette, Subfamily A, member 12 (ABCA12).[4]

These skin plates:

  • do not function as permeability barrier, leading to both water and heat loss
  • constrict body movements
  • cause malformations of the ears, eyelids and lips during development


Neuroblastoma (Image: NZ Crown copyright)
Links: Neuroblastoma | Neural Crest System - Abnormalities

OMIM Database Search: "Neuroblastoma"

Teeth Defects

amelogenesis imperfecta hypocalcification leads to soft enamal on teeth. Yellow dentine is visible through the thin layer of enamal.

dentinogenesis imperfecta odontoblasts fail to differentiate. Enamal of teeth wears excessively.

enamel hypoplasia environmental factors affecting ameloblast formation of enamal on teeth.

OMIM Database Search: "amelogenesis imperfecta" | "dentinogenesis imperfecta" | "enamel hypoplasia" |

Mammary Glands

Gynecomastia is stimulation by maternal sex hormones leads to excessive development of newborn male mammary glands. There are several possible causes of this excess estrogen in boys which also causes musculoskeletal abnormalities (premature growth spurt, early fusion of epiphyses, and decreased adult height).

OMIM Database Search: "Gynecomastia" (2005 - 44 search results)

Breast Cancer

In 1994, two breast cancer susceptibility genes were identified

  • BRCA1 on chromosome 17
  • BRCA2 on chromosome 13

When an individual carries a mutation in either BRCA1 or BRCA2, they are at an increased risk of being diagnosed with breast or ovarian cancer at some point in their lives. Normal function of these genes was to participate in repairing radiation-induced breaks in double-stranded DNA. It is though that mutations in BRCA1 or BRCA2 might disable this mechanism, leading to more errors in DNA replication and ultimately to cancerous growth.

Breast Cancer Detection reduce mortality is through early detection (general screening of the population for BRCA1 and BRCA2 is not yet recommended). New strategies to find anti-cancer drugs are constantly being developed. The latest, called 'synthetic lethal screening' looks for new drug targets in organisms such as yeast and fruit flies. In the same way that studies in yeast recently helped to identify the functions of BRCA1 and BRCA2, it is thought that drugs that work in more primative organisms will also be applicable to humans.

BreastScreen Australia monitoring report 2011-2012 - 1 Oct 2014 [5]

The BreastScreen Australia monitoring report 2011-2012 presents the latest national statistics on this national screening program, which aims to reduce illness and death resulting from breast cancer through organised screening to detect cases of unsuspected breast cancer in women, thus enabling early intervention.

  • Around 55% of women in the target age group of 50-69 took part in the program, with more than 1.7 million women screening in 2011-2012.
  • Breast cancer mortality is at an historic low, at 44 deaths per 100,000 women.

Vascular Abnormalities

Angiomas are vascular disorder resulting in excessive skin vascularisation.

OMIM Database Search: "Angioma" (2005 - 23 search results)

Skin Colour Abnormalities

There are many different factors that can affect skin colouration, some are genetically related while others are due to diet or pharmacological drug side effects.

EC23.2 Albinism

 ICD-11 EC23.2 Albinism or other specified genetically-determined hypomelanotic disorders - A large group of heritable disorders in which cutaneous melanin production is reduced or absent, mainly as the result of defects in enzymes required for normal melanin biosynthesis.

Albinism is generally an autosomal recessive trait resulting in lack of pigment in skin, hair and retina.

5B90.1 Hypercarotenaemia

 ICD-11 5B90.1 Hypercarotenaemia - Excessive intake of carotenoids is not associated with toxicity but can cause yellow coloration of the skin that disappears when intake is reduced. This disorder is especially likely to occur in children with liver disease, diabetes mellitus or hypothyroidism, and in those who do not have enzymes that metabolize carotenoids.

Carotenemia excess carotene intake results from eating large quantities of green and yellow vegetables, tomatoes, or yellow corn.


Jaundice is the yellow colour of skin and mucous membranes, and is generally not an abnormality of the skin. Often seen in newborn infants, due to accumulation of bile pigments in the blood and their deposition in body tissues. Note there are other pathological causes of jaundice.

Quinacrine used for treatment of giardiasis, produces a yellow skin color, but the urine remains normal.

OMIM Database Search: "albinism" | "Jaundice"


 ICD-11 2C30 Melanoma of skin

A primary melanoma arising from atypical melanocytes in the skin. Precursor lesions include acquired and congenital melanocytic nevi, and dysplastic nevi. Several histologic variants have been recognized, including superficial spreading melanoma, acral lentiginous melanoma, nodular melanoma, and lentigo maligna melanoma.
Melanoma heritability stratified by chromosome[6]

Melanoma develops postnatally when melanocytes become malignantly transformed, these transformed cells can then become invasive and spread to other tissues. Melanocytes (neural crest) normally protect the postnatal skin cells against ultraviolet radiation (UV) damage. Both UV light and genetics related to skin colour have roles in melanoma susceptibility.

There are several different melanoma forms:

  • Superficial spreading - most common type of melanoma about 70% of all melanomas.
  • Nodular - about 15% of all melanomas and becomes invasive soon after first appearing.
  • Acral-lentiginous - about 8% of all melanomas and is the most common melanoma in dark-skinned people.
  • Lentigo maligna - about 5% of melanomas.
  • Amelanotic - rare and has an absence of pigmentation.
  • Desmoplastic - rare about 1.7% of all melanomas.

Melanoma susceptibility is associated with chromosomes 6, 9, 11, 16; and the genes Cyclin-Dependent Kinase Inhibitor 2A (CDKN2A) and Methylthioadenosine Phosphorylase (MTAP) [6]

  • Cyclin-Dependent Kinase Inhibitor 2A 9p21.3 - role in regulating other cell cycle regulating pathways, p53 pathway and the RB1 pathway.
  • Methylthioadenosine Phosphorylase 9p21.3 - role in polyamine metabolism and the salvage of the amino acids adenine and methionine.

Links: SEER Training Module | CDKN2A | MTAP


  1. Malchin N, Sarig O, Grafi-Cohen M, Geller S, Goldberg I, Shani A, Gat A, Sprecher E & Mashiah J. (2016). A novel homozygous deletion in EXPH5 causes a skin fragility phenotype. Clin. Exp. Dermatol. , 41, 915-918. PMID: 27730671 DOI.
  2. Coolen NA, Schouten KC, Middelkoop E & Ulrich MM. (2010). Comparison between human fetal and adult skin. Arch. Dermatol. Res. , 302, 47-55. PMID: 19701759 DOI.
  3. Shin KC, Park BY, Kim HK, Kim WS & Bae TH. (2011). The use of cultured allogenic keratinocyte grafting in a patient with epidermolysis bullosa simplex. Ann Dermatol , 23, S393-7. PMID: 22346287 DOI.
  4. Zhang L, Ferreyros M, Feng W, Hupe M, Crumrine DA, Chen J, Elias PM, Holleran WM, Niswander L, Hohl D, Williams T, Torchia EC & Roop DR. (2016). Defects in Stratum Corneum Desquamation Are the Predominant Effect of Impaired ABCA12 Function in a Novel Mouse Model of Harlequin Ichthyosis. PLoS ONE , 11, e0161465. PMID: 27551807 DOI.
  5. AIHW 2014. BreastScreen Australia monitoring report 2011-2012. Cancer series no. 86. Cat. no. CAN 83. Canberra: AIHW.
  6. 6.0 6.1 Hulur I, Skol AD, Gamazon ER, Cox NJ & Onel K. (2017). Integrative genetic analysis suggests that skin color modifies the genetic architecture of melanoma. PLoS ONE , 12, e0185730. PMID: 28973033 DOI.



Search Pubmed

Search Pubmed: Integumentary congenital abnormalities | Ehlers-Danlos Syndrome | Epidermolysis Bullosa Simplex

Abnormality Links: abnormal development | abnormal genetic | abnormal environmental | Unknown | teratogens | ectopic pregnancy | cardiovascular abnormalities | coelom abnormalities | endocrine abnormalities | gastrointestinal abnormalities | genital abnormalities | head abnormalities | integumentary abnormalities | musculoskeletal abnormalities | limb abnormalities | neural abnormalities | neural crest abnormalities | placenta abnormalities | renal abnormalities | respiratory abnormalities | hearing abnormalities | vision abnormalities | twinning | Developmental Origins of Health and Disease |  ICD-11
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1915 Congenital Cardiac Disease | 1917 Frequency of Anomalies in Human Embryos | 1920 Hydatiform Degeneration Tubal Pregnancy | 1921 Anencephalic Embryo | 1921 Rat and Man | 1966 Congenital Malformations

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Cite this page: Hill, M.A. (2019, October 19) Embryology Integumentary System - Abnormalities. Retrieved from

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© Dr Mark Hill 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G