A 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.
This 19-year-old man with Christ-Touraine-Siemens syndrome has mild
frontal bossing with dry and sparse scalp hair, prominent supraorbital
ridges with scanty eyebrows, a depressed and wide nasal bridge (saddle
nose), and high and wide cheekbones with a flattened maxilla. The lips are
thickened, and the skin is dry with an atopic-like dermatitis. Partial
anodontia is present.
Anhidrotic Ectodermal Dysplasia; Hypohidrotic Ectodermal
This is the condition affecting the “Toothless Men of
Sind,” members of a Hindu kindred that resides in the vicinity of Hyderabad
(the capital of Andhra Pradesh in India) and was described by Charles Darwin
in 1875 and later by K.I. Thadani in 1934.
Approximately 1:100,000 of the general population is
X-linked recessive. The disease is caused by a
mutation in the ectodysplasin A gene (ED 1), which has been mapped to
Xq12.2-q13.1. As a member of the tumor necrosis factor ligand superfamily,
ectodysplasin is a membrane protein involved in signal transduction,
promoting not only cell adhesion to the extracellular matrix, but also
regulating the development of ectodermal appendages and
epithelio-mesenchymal interactions. Although usually only men are affected
and women act as carriers of the disease, the clinical picture in
heterozygous females is highly variable, ranging from no symptoms to severe
disease. Rarely, the disease is transmitted in an autosomal recessive or an
autosomal dominant pattern.
The clinical triad of anhidrosis (or hypohidrosis),
hypotrichosis, and defective dentition is helpful for diagnostic purposes.
Skin biopsy of the palm demonstrates the absence or hypoplasia of sweat
Often the disorder presents in the first year of
life with episodes of unexplained hyperpyrexia. Thermography can reveal
abnormal skin temperature patterns consistent with altered peripheral
vascular perfusion. The skin is abnormally dry (lack of sebum and sweat),
and heat loss by evaporation is impaired secondary to hypoplastic/aplastic
eccrine sweat glands. Associated features include characteristic facies
(frontal bossing, saddle nose, flattened maxilla, small chin), fine,
brittle, and scant hair (hypotrichosis), scant or absent eyelashes and
eyebrows, onychodysplasia (spoon-shaped nails), aplastic/hypoplastic mammary
glands with hypoplastic/absent nipples, and atopic-like dermatitis. Dental
anomalies include hypodontia/anodontia, taurodontism (tooth with abnormally short roots and
enlarged pulp chamber), and conical crowns.
Lacrimation and meibomian glands may be absent or diminished. Respiratory
tract mucous glands may be hypoplastic/aplastic, resulting in an increased
propensity to bronchitis and pneumonia. Laryngeal incompetence with dry
mucosal atrophy (often resulting in hoarse voice) is not uncommon and may
contribute to recurrent chest infections. A variable degree of mental
retardation may be present. Otherwise the prognosis ...