American Journal of Medical Genetics 72:462–467 (1997) Autosomal Dominant Hypohidrotic Ectodermal Dysplasia in a Large Family Andrew L. Aswegan,1 Kevin D. Josephson,2 Rodney Mowbray,3 Richard M. Pauli,4 Richard A. Spritz,4 and Marc S. Williams5* 1 Gundersen Medical Foundation, La Crosse, Wisconsin La Crosse Regional Genetic Services Project, La Crosse, Wisconsin 3 Department of Physics, University of Wisconsin, La Crosse, Wisconsin 4 Department of Pediatrics and Medical Genetics, University of Wisconsin Madison, Wisconsin 5 Department of Pediatrics, Gundersen Lutheran Medical Center, La Crosse, Wisconsin 2 We have studied an autosomal dominant hypohidrotic ectodermal dysplasia in 38 individuals over six generations in one family. Thirty-two affected individuals in four generations are still living. Questionnaire responses were received from 21 of the affected relatives and some of the individuals were examined by one of the authors. Smooth, dry, thin skin is seen in most affected individuals. Nearly all have fine, slow-growing scalp and body hair and all have sparse eyebrows and short eyelashes. Nearly all show a decrease in sweating, with some only sweating under the arms and/or on the palms and soles. All affected individuals lacked some deciduous teeth and some permanent teeth. Some teeth are abnormally shaped. Nail abnormalities are more variable and may occur more frequently with increasing age. No other abnormalities are seen in affected individuals in this family. We reviewed 40 autosomal dominant ectodermal dysplasia syndromes. This family bears some resemblance to a family described by Jorgensen et al. ; however, it appears to represent a disorder that has not been described previously. Am. J. Med. Genet. 72:462–467, 1997. © 1997 Wiley-Liss, Inc. KEY WORDS: ectodermal dysplasia; autosomal dominant; hypohidrotic INTRODUCTION Over 100 types of ectodermal dysplasia have been catalogued by Freire-Maia and Pinheiro , and over 40 of these are thought to be autosomal dominant traits [Online Mendelian Inheritance in Man, OMIM, 1996]. We report on a family with an autosomal dominant ectodermal dysplasia characterized by hypotrichosis, hypohidrosis, hypodontia with abnormally shaped teeth, and variable nail abnormalities. METHODS The family under study is known to contain 38 affected individuals over six generations (Fig. 1). Questionnaires were sent out and responses were received from 44 of the relatives. Where appropriate, a close relative completed the questionnaire for deceased relatives. Examination was performed on 26 individuals by one of the authors (MSW). CLINICAL DESCRIPTION Hair (Fig. 2) Abnormalities of hair are present in all affected individuals. Most individuals have sparse, fine, slowgrowing scalp hair. Some individuals (IV-20) were completely bald by their middle teens, whereas other individuals (V-1, V-2) have normal amounts of scalp hair, though abnormal in texture (V-1, fine, silky; V-2, coarse). Sparse eyebrows and eyelashes were always found. Most individuals show decreased body hair, pubic hair, and/or axillary hair, but these traits are more variable. Electron microscopy of hairs from affected and unaffected individuals in one branch of the family (V-57, V-65, VI-1, VI-2) showed no abnormalities. Skin *Correspondence to: Dr. Marc S. Williams, Gundersen Lutheran Medical Center, 1836 South Avenue, La Crosse, WI 54601. E-mail:[email protected] Received 13 December 1996; Accepted 14 February 1997 © 1997 Wiley-Liss, Inc. Most individuals report dry skin. Affected individuals have a smooth, almost velvety skin texture. The skin of affected individuals also seems to be ‘‘thinner’’ Fig. 1. Pedigree with autosomal dominant inheritance of an ectodermal dysplasia. N.B. Numbering is not consecutive in generations due to ascertainment of relatives at different times. Renumbering was not done as the numbers are being used as identifiers for mapping studies. Open symbols are patients unaffected by history. Crosses in symbols are patients unaffected on examination. Closed symbols are affected patients, with asterisks indicating patients who have been examined. 464 Aswegan et al. Fig. 2. Hypohidrotic Ectodermal Dysplasia 465 Fig. 2. Variable hair findings in family. A,B: Individual V-37 showing significant thinning and loss of scalp hair and thinning of eyebrows. Note preservation of facial hair. C,D: Individual IV-9 showing fine, thin hair. Eyebrows are absent (pt. uses cosmetics). E–H: Siblings V-1 and V-2 showing thick coarse scalp hair, but absent eyebrows. than expected for age. Some had venous prominence, but this was variable. A few individuals report ‘‘susceptibility to rashes.’’ Sweating Almost all affected relatives have decreased sweating and many show heat intolerance. Some individuals only sweat in certain areas on their body. Common sites of sweating include palms, soles, and axillae. Teeth (Fig. 3) Hypodontia and irregularly shaped primary incisors (conical or pointed) are a universal trait among affected individuals. All lacked some deciduous teeth, and nearly all lacked four lower permanent incisors. Some affected relatives lacked other permanent teeth, in descending order: upper incisors, canines, bicuspids. Most had a partial plate by their teens or twenties. Teeth were not discolored. Most affected individuals were not unusually susceptible to dental caries. Nails About half of affected individuals report mild fingernail abnormalities. Slow nail growth and split nails are reported most commonly. A few individuals had a longitudinal ridging, thinning, and superficial peeling. Nail problems occur more frequently in older individuals. This suggests that the nail beds are more susceptible to progressive injury with age. Toenails were generally normal. Facial Features Facial appearance is not particularly unusual. Mild frontal bossing and malar flattening is seen in most individuals. These changes appear to be common to many ectodermal dysplasias, and do not allow clinical distinction. Other Manifestations A few individuals complain of dry eyes, but most have normal tear production. This may also be associ- ated with increasing age. Production of saliva is normal. Females do not report decreased vaginal secretion. No hypermobility of joints was reported. There are no abnormalities of vision or hearing. Dermal ridges are generally normal, although a few older individuals have some ‘‘smoothing’’ of ridges. No other anomalies are present in this family. DISCUSSION This family’s disorder was compared to other autosomal dominant hypohidrotic, hypodontic, and hypotrichotic disorders, and all but two could be excluded with confidence. Both are described by Jorgenson [1974; Jorgenson et al., 1987] (Table I). In 1974, Jorgenson described a condition of dry skin, hypohidrosis, dystrophic nails, poor teeth, and hypotrichosis. The hypotrichosis included thin, coarse hair and sparse eyebrows and eyelashes. The affected persons in that family also had dry eyes, unusual dermatoglyphic patterns, and loose-jointedness. The condition described here does not comprise unusual dermatoglyphics, dry eyes, or loose-jointedness and the nail dystrophy in this family is much milder. The family described here and that of Jorgenson may not represent the same disorder. The report of Jorgenson et al.  included a boy and his mother with hypohidrosis, conical primary teeth, random lack of permanent teeth, hyperextensible joints, and hypotrichosis. The patients described here showed a specific pattern of absence of permanent teeth. The report of Jorgenson et al. also contains no mention of sparseness of eyebrows or eyelashes, which was universally found in this described family. Our patients also showed a decrease in body hair in the axillary and pubic regions. This was not found in the patients described by Jorgenson. However, these two families do share many major traits. Whether the minor clinical differences are sufficient to characterize these as two distinct autosomal dominant ectodermal dysplasias is not clear. However, we 466 Aswegan et al. Fig. 3. Dental findings. A,B: Individuals V-35 and V-37 showing pegshaped canine. C,D: Mother and daughter IV-9 and V-78 showing absence of two lower incisors (C) and absence of all lower incisors (D). Note also unusual form of canines and bicuspids. E: Individual VI-1: note pointed deciduous incisors. Hypohidrotic Ectodermal Dysplasia 467 TABLE I. Clinical Manifestations Number affected Finding Skin Smooth Dry Thin Hair Sparse Fine Slow growing Sparse eyebrows Sparse eyelashes Sparse body hair Sweating Decreased sweating Heat intolerance Nails Pits/ridges/splitting Teeth Delayed eruption Absent deciduous Absent permanent Conical teeth Our family 26 pts. Jorgenson et al., 1987 5 pts. Jorgenson, 1974 3 pts. 21 17 21 NRa 1 NR 1 3 NR 22 23 17 25 26 16 4 NR NR 0 0 NR 2 NR 2 1 1 NR 22 13 3 1 3 1 10 NR 3 12 22 26 21 1 2 4 4 0 1 3 0 a NR, not reported. think, as does Jorgenson (personal communication, 1996), that they probably represent distinct entities. REFERENCES Freire-Maia N, Pinheiro M (1984): ‘‘Ectodermal Dysplasias: A Clinical and Genetic Study.’’ New York: Alan R. Liss, Inc. Jorgenson RJ (1974): Ectodermal dysplasia with hypotrichosis, hypohidro- sis, defective teeth, and unusual dermatoglyphics (Basan syndrome?). New York: Alan R. Liss, Inc., for the National Foundation–March of Dimes. BD:OAS X(4):323–325. Jorgenson RJ, Dowben JS, Dowben SL (1987): Autosomal dominant ectodermal dysplasia. J Cranio Genet Dev Biol 7:403–412. Online Mendelian Inheritance in Man, OMIM (TM) (1996): Center for Medical Genetics, Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD).