Ectodermal Dysplasia

Ectodermal dysplasia is a rare group of inherited disorders. It was first described by Charles Darwin in 1875. The disorders arise from disturbances in one or more ectodermal structures and their accessory appendages. The absence, or deficient function, of at least two derivatives of the ectoderm constitutes a form of ectodermal dysplasia. Each combination of defects represents another type of ectodermal dysplasia and has a specific name. At least 150 different forms of ectodermal dysplasia have been identified; some of the most common are presented here.

Individuals affected with ectodermal dysplasia have at least two of the following manifestations:

• Absent or malfunctioning sweat glands. Temperature regulation can be dysfunctional and lead to hyperthermia.
• Dental anomalies, including missing or underdeveloped teeth.
• Varying degrees of alopecia resulting from defective hair follicles.
• Malformed or missing fingers or toes.
• Malformed fingernails and toenails.
• Cleft lip/palate, deficient saliva, hearing and visual defects, and inadequate eye fluids and tears.
• Neurologic and respiratory abnormalities may be present.

At a Glance

Autosomal dominant ectodermal dysplasia characterized by the triad of palmoplantar hyperkeratosis, nail dystrophy, and alopecia. Facial appearance, teeth, and sweating are normal.

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Synonyms

Fischer-Jacobsen-Clouston Syndrome; Hidrotic Ectodermal Dysplasia.

Incidence

Unknown. A higher incidence has been reported in the French Canadian population, but it occurs in all ethnicities.

Genetic Inheritance

Autosomal dominant. The defect has been linked to 13q11-q12.1.

Pathophysiology

Abnormality in the molecular structure of keratin seems to be responsible for the disease.

Diagnosis

Based on the typical clinical features and family history.

Clinical Aspects

In contrast to the X-linked form of ectodermal dysplasia (anhidrotic ectodermal dysplasia), most of the affected patients have normal sweat and sebaceous glands, and the teeth are usually only mildly affected (in contrast to the first description by Clouston). However, as in other forms of ectodermal dysplasia, the patients suffer from severe dystrophy of nails (thickened, striated, very slow growing, often discolored) and hair (resulting in total alopecia, sometimes in infancy but usually after puberty). Ultrastructural analysis of the hair shows an altered organization of hair fibrils with loss of the cuticular cortex suggesting a biochemical defect in the keratin of the integumentary system. Skin changes include palmoplantar hyperkeratosis, which can involve the periungual area and result in thickening of the fingertips with the aspect of clubbing. Skin hyperpigmentation is common over the joints.

Precautions before Anesthesia

Although no specific reports for this disease exist, because of mild depression of the immune system and hypoplasia/absence of the respiratory mucus glands, other forms of ectodermal dysplasia are often associated with a predisposition to respiratory tract infections, which can be life-threatening. Although no such reports exist specifically for this syndrome, it should be kept in mind when assessing the patient.

Anesthetic Considerations

Altered heat regulation does not seem to be a problem in these patients because sweat glands are functional. Direct laryngoscopy and tracheal intubation may be difficult because of maxillary and/or mandibular abnormalities. Because of hypoplasia/absence of mucous glands in the respiratory tract, humidified air should be used for general anesthesia and in the postanesthesia care unit.

Pharmacological Implications

No adverse drug reactions specific for this disease have been reported.

Other Conditions to Be Considered

Incontinentia Pigmenti: X-linked, dominant genodermatosis with skin pigmentation changes that are often associated with ocular, dental, and central nervous abnormalities and with malignancies (Wilms tumor, retinoblastoma, myeloid leukemia, rhabdomyosarcoma).

Ectrodactyly, Ectodermal Dysplasia, and Clefting (EEC) Syndrome: Autosomal dominant inherited anomaly complex characterized by ectrodactyly of hands and feet, ectodermal dysplasia, and cleft lip/palate.

Gorlin-Goltz Syndrome: Autosomal dominant transmitted neurocutaneous syndrome characterized by facial, skin, and skeletal abnormalities and later (usually after puberty) occurrence of multiple basal cell carcinomas.

Setleis Syndrome: Characterized by an aged leonine face with absent or multiple rows of eyelashes, redundant facial soft tissue, and rubbery feel to facial skin. Characteristic bitemporal skin marks and association with imperforate anus.

CHANDS: Autosomal recessive inherited form of ectodermal dysplasia associated with ankyloblepharon.

Christ-Siemens-Touraine Syndrome: Heterogeneous genetic disorder caused by abnormal development of the ectodermal tissue and characterized by the association of hypohidrosis, hypotrichosis, defective dentition, peculiar facies, abnormal thermoregulation, and exocrine gland insufficiency.

Oculodentodigital Syndrome: Ectodermal dysplasia with autosomal dominant inheritance characterized by mental retardation, microcephaly, microphthalmia, glaucoma, enamel hypoplasia, syndactyly and camptodactyly, and hypotrichosis.

Pachyonychia Congenita (Jadassohn-Lewandowsky Syndrome; Jackson-Lawler Type of Pachyonychia Congenita; Schaffer-Brunauer Syndrome (with steatocystoma multiplex); Nonepidermolytic Palmoplantar Keratoderma): Onychogryposis, hyperkeratosis of the palms, soles, knees, and elbows. Tiny cutaneous horns in many areas and leukoplakia of the oral mucosa.

Craniodiaphyseal Dysplasia: Bone disorder characterized by marked hyperostosis of the craniofacial bones and diaphyseal expansion of the tubular bones resulting in significant clinical complications.

Schopf-Schultz-Passarge Syndrome: Autosomal recessive inherited keratosis palmoplantaris with cystic eyelids, hypodontia, and hypotrichosis. Increased frequency of tumors of exocrine glands.

Carnevale-Hernandez-Castillotorres Syndrome: Extremely rare syndrome characterized by triphalangeal thumbs, brachy (syn)dactyly, and occasionally ectrodactyly of the feet and hands.

Trichodento-osseous Syndrome: Autosomal dominant inherited disorder featuring enamel hypoplasia and hypocalcification, combined with curly, dry hair.

Amelogenesis Imperfecta, Hypomaturation-Hypoplasia-Type with Taurodontism Syndrome: Clinically very similar to the trichodento-osseous syndrome. The dental changes are identical to those found in trichodento-osseous syndrome but without hair changes and osteosclerosis; however, it is reported to be genetically different.

Xeroderma, Talipes, and Enamel Defect Syndrome: Extremely rare, autosomal dominant inherited form of ectodermal dysplasia is characterized by xeroderma, talipes, and tooth enamel defects. Further signs include growth and mild mental retardation, congenital mitral stenosis, cleft palate, absent eyelashes of the lower lid, short-lasting skin vesicles, reduced number of sweat glands associated with hypohidrosis, and increased photosensitivity.

Onychotrichodysplasia with Neutropenia: Clinical signs of this extremely rare disorder, which is caused by an autosomal recessive mutation, include onychotrichodysplasia, chronic neutropenia, and mild mental retardation. However, patients with normal intelligence have been reported. Trichorrhexis nodosa with bamboo-like appearance of the hair results in brittle hair. Chronic neutropenia may be part of the so-called lazy leukocyte syndrome. No case reports related to anesthesia have been found, but strict asepsis seems mandatory in the perioperative care to prevent infections.

Odontotrichomelic Syndrome: Autosomal recessive inherited, extremely rare syndrome presents most often with severe absence deformities of all four extremities, abnormal teeth, hypoplastic nipples, malformation of the ears, absent or decreased eyelashes and eyebrows, and hypotrichosis. Other less frequent signs include nail anomalies, hypogonadism, thyroid enlargement and dysfunction, cleft lip, ECG and EEG abnormalities, and growth and mental retardation. Increased concentrations of tyrosine and/or tryptophane in the urine were reported.

Tooth and Nail Syndrome: Rare autosomal dominant ectodermal dysplasia characterized by defects of the nail plates of the fingers (onychorrhexis) and toes (koilonychia). Familial hypodontia with normal hair and sweat gland function.

Naegeli Ectodermal Dysplasia (Naegeli Franceschetti Jadassohn Syndrome): Autosomal dominant inherited disease, which is limited to the ectoderm (hypohidrosis, palmoplantar keratoderma, lack of dermatoglyphics [fingerprint lines], characteristic reticular hyperpigmentation on neck, chest, and abdomen, onychodystrophy and yellowish spots on their enamel). Other organ systems have not been reported to be affected; mental retardation particularly is not a feature of this disease.

Tricho-Rhino-Phalangeal Dysplasia: Most often autosomal dominant inherited syndrome with mental retardation, microencephaly, multiple exostoses, musculoskeletal dysplasia, and redundant skin.

Monilethrix: Although the symptoms of these syndromes may resemble ectodermal dysplasia, it is suggested that monilethrix does not belong to this group. It is an autosomal dominant disorder characterized by a beaded appearance (because of periodic narrowing of the shaft) of the scalp hair as a result of periodic thinning of the shaft. The cause of this disease seems to be a mutation in the genes responsible for the hair keratin, which has been mapped to 12q13. Phenotypically, this results in breakage of the hair (brittle, dry, lusterless look) and patchy alopecia. Onset usually is in infancy, and symptoms may ameliorate to a certain degree after puberty and during pregnancy.

References