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Hidrotic Ectodermal Dysplasia

Syndrome Clouston's

Hidrotic ectodermal dysplasia is an autosomal dominant disorder characterized by the abnormal development and growth of ectodermal tissues such as the nails, hair, and skin. The degree of severity is varies even among affected family members. It is more commonly observed in individuals of French-Canadian descent although it is reported in people from other backgrounds as well.


Presentation

The clinical picture of hidrotic ectodermal dysplasia varies even among family members but the typical clinical triad consists of nail dysplasia, alopecia, and palmoplantar hyperkeratosis.

Nails

In this disorder, the nails are malformed, hypoplastic, thick, discolored (milky white), and unattached to the nail bed. Additionally, the deformed nails are prone to recurrent paronychial infections [7], which can lead to nail loss. Note that these nail changes are the sole features in about 30% of patients at the time of examination. These features appear at birth or in infancy.

Hair

Affected individuals may exhibit brittle, sparse, patchy, and pale scalp hair that may progress to full alopecia by puberty. The hair loss may be partial or complete. Moreover, eyebrows, eyelashes, axillary and pubic hair may be partially or fully absent [8]. Hair features develop as early as birth or as late as childhood.

Skin

Palmoplantar hyperkeratosis in childhood is another frequently observed sign but is not consistently observed. This can worsen with age.

Another dermatological finding is hyperpigmentation, which can be particularly found on the elbows, knees, and joints of the fingers and toes [8] [9].

Other

Other tissues such as the teeth, sweat glands, and sebaceous glands are not affected [8] [10]. The patient's physical growth and development are also normal.

Further manifestations may include sensorineural deafness and skeletal abnormalities such as syndactyly and polydactyly [8] [9]. Ocular complications such as strabismus, conjunctivitis, pterygium, and cataract may also develop [10]. Finally, clubbing of the fingers may also occur.

Short Stature
  • Short stature (5-10th centile) present in some cases is possibly a separate familial trait. The family demonstrates overlapping features with Clouston syndrome.[ncbi.nlm.nih.gov]
  • stature (usually mild) Diagnosing Clouston Syndrome A physician can diagnose Clouston syndrome on the basis of physical features.[nfed.org]
  • Short stature (5-10th centile) present in some cases is possibly a separate familial trait. The family demonstrates overlapping features with Clouston syndrome .[journals.lww.com]
  • Short stature, mental deficiency (rare and not typically severe), clubbing of the digits and ocular issues (strabismus, cataracts, conjunctivitis, blepharitis, myopia) have been associated with this condition. Life span is normal.[dermatologyadvisor.com]
  • stature, craniofacial dysmorphism, and congenital heart defects B3GAT3 Muscular dystrophy-dystroglycanopathy FKTN Myelodysplastic syndrome, somatic TET2 Myoclonus Dystonie SGCE Myopathy due to myoadenylate deaminase deficiency AMPD1 Myotonia Congenita[meduniwien.ac.at]
Fishing
  • Fiber-FISH and FISH on interphase nuclei analyses with PACs isolated from this region supported our order. We also describe the isolation of 8 new chromosome 13q polymorphic (CA)n markers that have an average PIC value of 0.67.[ncbi.nlm.nih.gov]
Congestive Heart Failure
  • He died at age 29 in congestive heart failure from rheumatic pancarditis. At autopsy, concretions were identified in globus pallidus, caudate nuclei, thalamus, and dentate nuclei.[ncbi.nlm.nih.gov]
Swelling
  • […] biochemical investigations in hidrotic ectodermal dysplasia have demonstrated that the abnormal hair exhibits lower levels of disulfide bonds and cysteine, which account for the hair thinness as well as its decreased tensile strength and an unusual swelling[symptoma.com]
Palpitations
  • One of the patients had supraventricular tachycardia, another had palpitations, and two others had sinus brachycardia.[ncbi.nlm.nih.gov]
Macrocephaly
  • Relative macrocephaly due to hyperostosis of the cranial vault was variably present. Short stature (5-10th centile) present in some cases is possibly a separate familial trait. The family demonstrates overlapping features with Clouston syndrome.[ncbi.nlm.nih.gov]
  • Relative macrocephaly due to hyperostosis of the cranial vault was variably present. Short stature (5-10th centile) present in some cases is possibly a separate familial trait. The family demonstrates overlapping features with Clouston syndrome .[journals.lww.com]
No Pubic Hair
  • hair Clinical features from OMIM: 601375 Human phenotypes related to Ectodermal Dysplasia, Hidrotic, Christianson-Fourie Type: 59 32 (show all 16) # Description HPO Frequency Orphanet Frequency HPO Source Accession 1 sparse eyelashes 59 32 hallmark ([malacards.org]
  • Moreover, eyebrows, eyelashes, axillary and pubic hair may be partially or fully absent. Hair features develop as early as birth or as late as childhood.[symptoma.com]
  • ., moustache and beard) can be normal, while in other cases, facial and pubic hair growth may be sparse. In affected males and females, pubic and underarm (axillary) hair is typically scant.[rarediseases.org]
  • The eyelashes, eyebrows, underarm (axillary) hair, and pubic hair are also sparse or absent. Abnormal growth of fingernails and toenails (nail dystrophy) is also characteristic of Clouston syndrome.[ghr.nlm.nih.gov]
  • Axillary and pubic hair is sparse or absent. Palmoplantar hyperkeratosis (hyperkeratosis of the palms and soles); a common but not universal finding Molecular Genetic Testing Gene.[ncbi.nlm.nih.gov]

Workup

Young children who present with the clinical triad of nail dystrophy, hypotrichosis, and palmoplantar hyperkeratosis should be evaluated for this disorder. Mild manifestations are diagnosed in childhood when the patients display abnormal growth and maturation of the nails or hair. However, severe cases are recognized in infancy.

The clinical assessment involves a full medical and family history, a complete physical exam (especially of the nails, hair, and skin) and key studies.

Molecular genetic testing offers confirmation of the diagnosis. Specifically, targeted mutation analysis identifies the most prevalent pathogenic variants in nearly 100% of patients with this disorder. The second-line test, sequence analysis, is performed if the targeted mutation analysis is not conclusive.

Treatment

The therapeutic approach aims to address the manifestations. In terms of nail dystrophy, patients may wear artificial nails to improve appearance. Hair can be managed with wigs and special hair products. Furthermore, topical minoxidil and tretinoin may be beneficial for hair growth in patients with alopecia. Finally, palmoplantar hyperkeratosis may be treated with skin emollients, keratolytics, and topical vitamin D, and topical and systemic retinoids.

Special consideration

Prenatal counseling can be offered for individuals with this genetic disorder and those with a positive family history. The optimal time for genetic counseling is preconception. Education about what the disorder entails, its cause, how it is transmitted, and other concerns can be provided to help couples plan accordingly. Additionally, genetic testing can be made available.

Prognosis

Patients with hidrotic ectodermal dysplasia have a normal life span and good quality of life. The condition is manageable with supportive measures such as wearing artificial nails and wigs.

Etiology

Hidrotic ectodermal dysplasia is an autosomal dominant disorder resulting from mutations in the gene known as GJB6, which codes for the gap junction protein connexin 30. As the name suggests, connexins form channels between the cytoplasm of adjacent cells.

This pattern of inheritance was first recognized in a French Canadian family by Clouston in 1929 as he studied a 5 generation family in Quebec [1]. Specifically, the inheritance exhibits complete penetrance but variable clinical expression [4].

While the majority of cases are inherited through an autosomal dominant pattern, a few are acquired through de novo mutations.

Epidemiology

While the prevalence of hidrotic ectodermal dysplasia has not been elucidated, this disorder has been observed particularly in those with French Canadian ancestry [5]. Specifically, there are reported cases in the French Canadian communities in Quebec as well as Louisiana, Vermont, and upstate New York.

Other populations noted to have this condition are the African, Chinese, Malaysian, Welsh, Irish, Danish, French, Spanish, German, and Ashkenazi Jewish.

Overall, hidrotic ectodermal dysplasia is likely underdiagnosed and more common than believed to be.

Sex distribution
Age distribution

Pathophysiology

This disorder is one of many ectodermal dysplasias classified under a group of disorders that involve ectodermal structures.

This particular condition is caused by a mutated GJB6 gene (locus 13q12), which codes for connexin 30, the gap junction protein that is found in various tissues such as the skin, nail beds, and hair follicles. Alteration in this gene results in impaired growth, division, and maturation of the cells of these tissues.

Analytical biochemical investigations in hidrotic ectodermal dysplasia have demonstrated that the abnormal hair exhibits lower levels of disulfide bonds and cysteine, which account for the hair thinness as well as its decreased tensile strength and an unusual swelling capacity [6]. Furthermore, the reduction in disulfide bonds is likely responsible for the disorganization of hair fibrils and cuticle desquamation [1]. In conclusion, these cumulative findings indicate abnormal molecular changes in keratin.

Prevention

Since this is an inherited disorder, it cannot be prevented. However, prenatal counseling and testing can be offered for individuals planning a family planning or those those already expecting.

Summary

Hidrotic ectodermal dysplasia (also known as Clouston syndrome) is a rare, autosomal dominant disorder initially described in the French-Canadian population in 1895 [1] [2] [3]. The etiology of this disorder is secondary to a mutation in the GJB6 gene that encodes a gap junction protein. Furthermore, hidrotic ectodermal dysplasia affects ectodermal structures and thus features the clinical triad of nail dystrophy, hair loss, and palmoplantar hyperkeratosis while sparing the teeth and sweat glands.

Deformities of the nails are the most predominant manifestations and usually appear at birth or in infancy. The nails are brittle, small, discolored, separated from the nail bed, and vulnerable to paronychial infections. Moreover, hair abnormalities develop at birth, infancy, or childhood and include partial or complete hair loss on the scalp, axillary, and pubic regions. Additionally, thickening of the palms and soles does not always occur. Further findings may include clubbing of the fingers, skin hyperpigmentation over the joints, sensorineural hearing loss as well as musculoskeletal and ocular abnormalities. However, the physical growth is unaffected.

Infants or children presenting with these manifestations should be suspected to have this disorder. The workup will consist of a medical and family history, a detailed physical examination, and molecular genetic testing. Specifically, targeted mutation analysis is the confirmatory diagnostic tool.

The treatment focuses on supportive measures such as applying artificial nails, wigs, and special hair products. Also, skin emollients, keratolytics, and other therapies may be used for the hyperkeratosis.

While this is not a preventable disorder, prenatal counseling and testing are options for affected individuals, those with a positive family history, eligible couples planning to have children.

Patient Information

What is hidrotic ectodermal dysplasia?

This is an uncommon genetic condition that affects the nails, hair, skin, and eyes. The gene responsible for this has a mutation (alteration). The majority of patients that have this disease have an affected parent. This type of inheritance is called autosomal dominant. In other words, the patient received one mutated (bad) copy of the gene from the affected parent and a good copy of the gene from the other parent.

In a few cases, the patient has a spontaneous mutation without affected parents or family members.

Which populations does this disorder affect?

Hidrotic ectodermal dysplasia is more commonly seen in people of French-Canadian descent such as the French-Canadian communities in Quebec, Louisiana, New York and Vermont.

Additionally, it is reported in people from other backgrounds such as African, Chinese, Malaysian, Welsh, Irish, Danish, French, Spanish, German, and Ashkenazi Jewish.

What are the signs and symptoms of this disorder?

The 3 main features of this condition are nail changes, hair loss, and thickening of the skin on the palms and soles. Also, skin discoloration is common. Nails are usually:

The following are the characteristics of the hair loss:

  • Hair is brittle, patchy, and pale
  • Slow hair growth
  • Partial scalp hair loss may progress to complete hair loss
  • Eyebrows, eyelashes, body and pubic hair may be partially or completely absent

The skin may be darker on the:

  • Knees
  • Elbows
  • Joints of the fingers
  • Joints of the toes

Patients may also have:

How is this diagnosed?

When a child presents with the above signs, the clinician will suspect this disorder as the diagnosis. The test that confirms hidrotic ectodermal dysplasia is genetic testing that identifies the genetic mutation.

How is it treated?

There is no specific treatment. However, artificial nails can help improve the appearance of the patient's nails, especially in girls and women.

Also, wigs and hair products can be used for individuals with fragile hair or alopecia.

Thickened skin on the palms and soles can be treated by skin emollients or keratolytics.

Family planning

The best time for learning about genetic risk is during the family planning stage. Individuals with an affected family member(s) and expecting parents have the opportunity to seek genetic counseling and genetic testing. Specifically, genetic counseling provides significant education about what this disorder means, how it is inherited, and the probability of passing this condition to offspring.

What is the prognosis?

Patients have a normal life expectancy. The manifestations of hidrotic ectodermal dysplasia can be managed by measures that improve appearance and confidence.

Can it be prevented?

This disorder is inherited and therefore cannot be prevented.

References

Article

  1. Clouston HR. A hereditary ectodermal dystrophy. Canadian Medical Association Journal. 1929. 21:18-31.
  2. Pierard GE, Van Neste D, Letot B. Hidrotic ectodermal dysplasia. Dermatologica. 1979. 158(3):168-74.[Medline].
  3. Reynold JM, Gold MB, Scriver CR. The characterization of hereditary abnormalities of keratin: Clouston's ectodermal dysplasia. Birth Defects Original Article Series. 1971; 7(8):91-5.
  4. Williams M, Fraser FC. Hydrotic ectodermal dysplasia--Clouston's family revisited. Canadian Medical Association Journal. 1967;96(1):36-8.
  5. George DI Jr, Escobar VH. Oral findings of Clouston's syndrome (hidrotic ectodermal dysplasia). Oral Surgery, Oral Medicine, and Oral Pathology. 1984;57(3):258-62.
  6. Gold RJ, Scriver CR. Properties of hair keratin in an autosomal dominant form of ectodermal dysplasia. American Journal of Human Genetics. 1972;24(5):549-61.
  7. Ando Y, Tanaka T, Horiguchi Y, Ikai K, Tomono H. Hidrotic ectodermal dysplasia: a clinical and ultrastructural observation. Dermatologica. 1988;176(4):205-11.
  8. Jan AY, Amin S, Ratajczak P, Richard G, Sybert VP. Genetic heterogeneity of KID syndrome: identification of a Cx30 gene (GJB6) mutation in a patient with KID syndrome and congenital atrichia. Journal of Investigative Dermatology. 2004; 122(5):1108-13.
  9. Tan E, Tay YK. What syndrome is this? Hidrotic ectodermal dysplasia (Clouston syndrome). Pediatric Dermatology. 2000;17(1):65-7.
  10. Wilkey WD, Stevenson GH. Family with Inherited Ectodermal Dystrophy. Canadian Medical Association Journal. 1945;53(3):226-30.

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Last updated: 2019-07-11 20:17