Clouston's hidrotic ectodermal

dysplasia Dysplasia is any of various types of abnormal growth or development of cells (microscopic scale) or organs (macroscopic scale), and the abnormal histology or anatomical structure(s) resulting from such growth. Dysplasias on a mainly microscopic ...

is a medical condition caused by

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

s in a

connexin Connexins (Cx)TC# 1.A.24, or gap junction proteins, are structurally related transmembrane proteins that assemble to form vertebrate gap junctions. An entirely different family of proteins, the innexins, forms gap junctions in invertebrates. Eac ...

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

, GJB6 or connexin-30, characterized by scalp hair that is wiry, brittle, and pale. It is often associated with patchy

alopecia Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarring ...

.Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed.). McGraw-Hill. .

Presentation

Hidrotic ectodermal dysplasia 2, or Clouston syndrome (HED2) is characterized by partial or total alopecia,

dystrophy Dystrophy is the degeneration of tissue, due to disease or malnutrition, most likely due to heredity. Types * Muscular dystrophy ** Duchenne muscular dystrophy ** Becker's muscular dystrophy ** Myotonic dystrophy * Reflex neurovascular dy ...

of the nails,

hyperpigmentation Hyperpigmentation, also known as the dark spots or circles on the skin, is the darkening of an area of Human skin, skin or nail (anatomy), nails caused by increased melanin. Causes Hyperpigmentation can be caused by sun damage, inflammation, or ...

of the

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...

(especially over the

joint A joint or articulation (or articular surface) is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole.Saladin, Ken. Anatomy & Physiology. 7th ed. McGraw- ...

s), and clubbing of the fingers. Sparse scalp hair and dysplastic nails are seen early in life. In

infancy In common terminology, a baby is the very young offspring of adult human beings, while infant (from the Latin word ''infans'', meaning 'baby' or 'child') is a formal or specialised synonym. The terms may also be used to refer to juveniles of ...

, scalp hair is wiry, brittle, patchy, and pale. Progressive

hair loss Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarring ...

may lead to total alopecia by

puberty Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a female, the testicles i ...

. The nails may be milky white in early childhood and then gradually become dystrophic, thick, and distally separated from the nail bed.

Palmoplantar keratoderma Palmoplantar keratodermas are a heterogeneous group of skin disorders characterized by abnormal thickening (scleroderma) of the stratum corneum of the palms and soles. Autosomal recessive, dominant, X-linked, and acquired forms have all been de ...

may develop during childhood and increases in severity with age. The clinical manifestations are highly variable even within the same family.

Genetics

HED2 is inherited in an

autosomal An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosome ...

dominant manner. Most individuals with HED2 have an affected parent. De novo

gene mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis ...

s have also been reported. Offspring of affected individuals have a 50% chance of inheriting the mutation and being affected.

Diagnosis

HED2 is suspected after infancy on the basis of

physical features Physical attractiveness is the degree to which a person's physical features are considered aesthetically pleasing or beautiful. The term often implies sexual attractiveness or desirability, but can also be distinct from either. There are many ...

in most affected individuals. GJB6 is the only gene known to be associated with HED2. Targeted mutation analysis for the four most common GJB6 mutations is available on a clinical basis and detects mutations in approximately 100% of affected individuals.

Sequence analysis In bioinformatics, sequence analysis is the process of subjecting a DNA, RNA or peptide sequence to any of a wide range of analytical methods to understand its features, function, structure, or evolution. It can be performed on the entire genome ...

is also available on a clinical basis for those in whom none of the four known mutations is identified.

Screening

Prenatal testing Prenatal testing is a tool that can be used to detect some birth defects at various stages prior to birth. Prenatal testing consists of prenatal screening and prenatal diagnosis, which are aspects of prenatal care that focus on detecting problem ...

for

pregnancies Pregnancy is the time during which one or more offspring gestates inside a woman's uterus. A multiple pregnancy involves more than one offspring, such as with twins. Conception usually occurs following vaginal intercourse, but can also o ...

at increased risk is possible if the disease-causing mutation in an affected family member is known; however, requests for prenatal testing for conditions such as HED2 are not common.

Treatment

HED2 symptoms can be treated with special hair care products to help manage dry and sparse hair, wigs, artificial nails and

emollients A moisturizer, or emollient, is a cosmetic preparation used for protecting, moisturizing, and lubricating the skin. These functions are normally performed by sebum produced by healthy skin. The word "emollient" is derived from the Latin verb ''mo ...

to relieve palmoplantar hyperkeratosis.

Presentation

Genetics

Diagnosis

Screening

Treatment

See also

References

Further reading