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Autosomal recessive hypohidrotic ectodermal dysplasia: Dental manifestations
Autosomal recessive hypohidrotic ectodermal dysplasia: Dental manifestations Richard C. Bartlett, D.iIl.D.,* Lewy R. Ellersole, Robert S. Adkins, D.M.D., Lezi?lgto?l, Ky. UNIVERSITY
OF KENTUCKY
COLLEGE
D.D.S.,
N.X.D.,**
md
OF DENTISTRY
Hypodontia, together with other characteristics similar in each of three sisters, established a diagnosis of anhidrotic ectodermal dysplasia. The clinical features of the patients are described, and the oral and dental manifestations are presented. The parents were found to be free of all the aberrant conditions described in the proband.
H
ereditary ectodermal dysplasia (HED) is characterized by a triad of anomalies, including sweat gland aplasia, hypotrichosis with lanugo, and hypodontia. In addition, dermatographic alterations have been recorded, and frontal bossing wit.h a depressed nasal bridge is commonly enc0untered.l This syndrome complex is usually inherited as an X-linked recessive trait.*, S Recently, PassBarge and Gorlin” and their co-authors have indicated that some cases of HED appear to follow an autosomal mode of transmission; yet, phenotypically, no differences have been encountered between persons manifesting the disease via the two different modes of inheritance. Passarge and associateq4 reported the occurrence of HED in three girls who were the progeny of unaffected parents. They reported that the pedigree indicated numerous instances of consanguinity, including the probands’ parents. They outlined the clinical features of the phenotype but presented no information regarding dental manifestations. For this reason, we are reporting the dental and oral manifestations of the female proband reported by Passarge and co-workers as an autosomal recessive form of HED. *Associate Professor, of Patient Care. **Assistant Professor,
736
Department Department
of Oral of Oral
Diagnosis Pathology.
and Oral
Medicine,
and Coordinator
Hypohidrotic
ectodermal
dysplasia
737
REPORT OF THREE CASES Three young sisters, 7, 10, and 12 years of age, were examined for dental disease in a school-sponsored multiphasic screening program. The dental findings (hypodontia), together with other characteristics similar in each child, established a diagnosis of anhidrotic ectodermal dysplasia and led to an interesting investigation of the genealogy, the highlights of which have been published.4 The complaints, signs and symptoms, and findings in all three patients were essentially the same. During the summer the patients experienced extreme discomfort from the heat and spent much of their time in the waters of a nearby creek in au effort to keep cool. During the winter months they all suffered frequent upper respiratory infections. The parents said: “They choke up and can hardly breathe. They turn blue sometimes while coughing and finally spit up black grisly things.” They were all said to “pass out when they get mad.” the children examined and treated on iilthough psychologic testing was not done, several occasions were mentally alert; they responded to questions and, in general, cornmunicated well with the examiners. V. S., 12 years of age at the time of the examination, weighed 89 pounds and was 54 inches in height. E. S., age 10, was described by the parents as “sickly.” She weighed 46% pounds and was 48J/ inches in height. G. S., age 7, weighed 45 pounds and was 4455 inches in height. The temperature of each child was 98.6’ F. The parents were subjected to the same type of examination as the children and were found to be free of all the aberrant conditions described here. The father weighed 168 pounds and was 66Jh inches in height. The mother weighed 109 pounds and was GOJ/z inches tall. Examination
findings
Fcbcies. The face of each child bore the characteristic features commonly reported to be associated with the syndrome (Fig. l), including a saddle nose or absence of the nasal bridge, everted lips, prominent chin, and frontal bossing. The ears were prominent, and the tragi were vestigial or absent in all three children. Eyes. In all three children the eyes appeared to lack luster, but the parents reported that the rhildren shed tears. There was a whitish discharge of the eyes in each patient. None of the children had eyebrows, and the lashes, though normal in length, were sparse. The wrinkled skin of the eyelids (Fig. 2) appeared to be thin, and there was a marked increase in the palpebral and periorbital pigmentation (Figs. 1 and 2). All of the children complained of photophobia. Respiratory tract. Dryness of the nasal and pharyngeal mucosa was noted in each patient. A dark green phlegmlike material was observed in the pharynx of each child, and the dryness of the mucosa was thought to be responsible for or associated with the hoarseness or laryngitislike speech. There was an irritation of the nasal mucosa in each child. Hair. The hair of the head of each patient was sparse and silky fine in texture. The hair was short, although it had never been cut, and it was evenly distributed (Fig. 1). With the exception of the sparse eyelashes, no other hair could be detected on the body. Slain. The entire body appeared to be extremely dry. The arms and legs were very smooth to touch. The wrists and ankles were extremely rough and tough. The forehead was smooth, but the cheeks were quite rough and scaly. The nipples of each girl were rudimentary, evidenced only by an area of slight pigmentation. Ha&s and feet. Although the cuticle was unkept, the nails of the fingers and toes were and color. In shape, however, the nails well developed. They were normal in size, thickness, were similar to the nails associated with distal phalangeal clubbing seen in patients with congenital heart deformities (Fig. 3). The fingers were prominently tapered (Fig. 4). The palms of the hands, shriveled in appearance, were rough, and the soles of the feet were tough and leathery. Oral findings. There was a characteristic eversion of the lips, and the vermilion borders were poorly defined. The only erupted teeth in each child were the peg-shaped maxillary canines (Fig. 5). Panoramic radiographs revealed three conical impacted teeth in the region of the mandibular symphysis in Patient E. S. (Fig. 6) and one such impaction in the symphysis of
Fig. 1. A and B, Patient V. S., age 12 ; C and D, Patient G . S., age 7. There were striking similarities in the proband. a saddle nose, everted lips, a prominent chin, and frontal in crease in the palpebral and periorbital pigmentation.
E. S., age 10; E and F, P atient Each of the three childre n had bossing. There was :I m arked
Volume Number
33 5
Fig. 8. The eyelashes were sparse, lids were wrinkled in all the patients.
Fig. however, pnt,ients
Hypohidrotic
and there
was a complete
ectodermal
absence
dysplasia
of eyebrows.
739
The
eye-
8. The nails of the fingers and toes were normal in size, thickness, and color. In shape, the nails were similar to the nails associated with distal phnlangeal clubbing seen in with congenital heart deformities.
Patient V. 8. Patient G. 5. had no such impactions. None of the children had lost any teeth. The alveolar ridges were firm and knife edged but extremely low in height, especially in the posterior mandibular areas. Xerostomia was observed in each child, in spite of the fact that milking of the salivary glands produced a scant amount of clenr fluid.
COMMENTS
Congenital absence of teeth is cncounterctl in a. variety of populations and often follows a hereditary pattern. Gl7 In addition, hypodontia may accompany other ectodermal and mesodermal anomalies, including X-linked recessive hypohidrotic ectodermal dysplasia,1-3 autosomal recessive hypohidrotic ectodermal dysplasia,4p5 autosomal dominant dysplasia of nails with hypodontia,8 chondroectodermal dysplasia (Ellis-Van Creveld syndrome) ,g, lo mesoectodermal dysgenesis of iris and cornea with myotonic dystrophy (Rieger’s syndrome),ll premolar dysplasia with premature whitening of hair and palmoplantar hyperhidrosis (B%k’s syndrome) ,I* Marshall’s syndrome,13 and incontinentin pig-
F’iu.
Fig. were
4. The
fingers
were
5. The intraoral findings in each child the peg-shaped maxillary canines.
prominently
were
remarkably
tapered.
similar.
The
only
erupted
teeth
mcnti.14 The patients presented here displayed all of the features usually cncountered in X-linked HED in that thin hair of the lanugo t,ype, hypodontia, and heat intolerance were present in each. In addition, prominent labial protrusion, a depressed nasal bridge, and frontal bossing were present. Gorlin and associates5 have discussed the reported cases of HED occurring in females with regard to possible mechanisms of inheritance. ln affected females the full phenotypic expression of HED, as in the cases reported here, may be the product of an X-linked recessive mode of transmission if the offspring were the product of an affected male and a carrier female. Alternatively, a partial deletion of the noi+mal, paternally derived X-chromosome correspond-
Volume 33 Number 5
Hypohidrotic
ectodermal
dysplasia
741
Fig. 6. Panoramic radiographs revealed three conical teeth in the mandibular symphysis of one of the patients. One of the children had one similar impaction, and the other child had none.
ing to the affected allele on the maternally derived X-chromosome could result in expression of the phenotype in one sibling, but the occurrence of deletion in three members of the sibship is extremely unlikely. The Lyon hypothesis could explain the occurrence of affected females in an X-linked recessive mode of inheritance. The absence of the trait in four generation9 of the kindred reported here, in combination with the prevalence of consanguinity and the finding of three affected females in the proband, are most compatible with an autosomal recessive trait. Since the phenotype in both the X-linked and autosomal recessive forms of HED are clinically identical, it appears that HED can be considered to be genetically heterogeneous. In the casesreported here, the heterozygous parents displayed no manifestations of the trait. Detailed analyses with regard to salivary and sweat gland secretions have not been pursued in these children. Such studies, however, might prove useful in identifying heterozygotes if biochemical differences should be observed. SUMMARY Hereditary ectodermal dysplasia in three sisters has been described. Their pedigree indicated numerous instances of consanguinity, including the parents of the proband. This syndrome complex may be inherited as an X-linked recessive trait, or it may follow an autosomal mode of transmission as in the cases presented here. Regardless of the mode of transmission, however, the phenotypic expressions are the same.
REFERENCES
1. Gorlin, 11. J., and Pindborg, J. J. : Syndromes of the lfentl and Srck, New York, 1964, McGraw-Hill Book Com-Danv. Inc.. UD. 303-311. 2. Franceshetti, A. : Les &spiasies’e%odermiques, Dermatologica 106: 129-156, 1953. 3. McKusick, V. A.: On the X Chromosome of Man, Baltimore, 1964, Waverly Press. 4. Passarge, E., Nuzum, C. T., and Schubert, W. K.: Anhidrotic Ectodermal Dysplasia as Autosomal Recessive Trait in an Inbred Kindred. Humangenetik 3: 181-185, 1966. 5. Gorlin, R. J., Old, T., and Anderson, V. E.: Hypohidrotic Ectodermal Dysplasia in Females: A Critical Analysis and Argument for Genetic Heterogeneity, Z. Kinderheilkcl. 108: l-11, 1970. 6. Woolf, C. M.: Missing Maxillary Lateral Incisors: A Genetic Study, Am. J. Hum. Genet. 23: 289-296, 1971. 7. GrahnBn, H.: Hereditary Factors in Relation to Dental Caries and Congenitally Missing Teeth. In. Witkop, C. J. (editor) : Genetics and Dental Health, New York, 1962, McGrawHill Book Company, Inc., pp. 194-204. 8. Witkop, C. J.: Genetic Disease of the Oral Cavity. In Tiecke, R. W. (editor) : Oral Pathology, New York, 1965, McGraw-Hill Book Company, Inc., p. 812. 9. Ellis, R. W. B., and Van Creveld, 8.: Syndrome Characterized by Ectodermal Dysplasia, Polydactyly, Chondro-Dysplasia and Congenital Morbus Cordis, Arch. Dis. Child. 15: 65-84, 1940. 10. Douglas, W. F., Schonholtz, G. J., and Geppert, L. J.: Chondroectodermal Dysplasia (Ellis-Van Creveld Svndrome) Am. J. Dis. Child. 97: 473-478. 1959. II. hieger, H. : Beitra@ zur genntnis seltenrr Missbildungen ’ der Iris, Graefes Arch. Ophthalmol. 133: 602-635, 1935. 72. Biib;k, J. A.: Clinical and Genetic Studies of Hypodontia. I. Premolar Aplasia, Hyperhidrosis, and Canities Prematura: A New Hereditary Syndrome in Man, Am. J. Hum. Genet. 2: 240-263, 1950. 13. Marshall. D.: Ectodermal DvsDlasia : A Report of Kindred With Ocular Almormnlitic,s and Hearing Defect, Am. J. ~p~hthalmol. 45:&143-156: 1958. 14. Gorlin, R. J., and Anderson, J. A.: The Characterlstie Dentition of Incontinentia Pigmenti (Rloch-Sulzberger Syndrome): A Diagnostic Aid, J. Pediatr. 57: 78-85, 1960. Eeprint
requests
Dr. Richard Department University Lexington,
to :
C. Bartlett of Oral Diagnosis and Oral Medicine of Kentucky College of Dentistry Kp. 40506
OF KENTUCKY
COLLEGE
D.D.S.,
N.X.D.,**
md
OF DENTISTRY
Hypodontia, together with other characteristics similar in each of three sisters, established a diagnosis of anhidrotic ectodermal dysplasia. The clinical features of the patients are described, and the oral and dental manifestations are presented. The parents were found to be free of all the aberrant conditions described in the proband.
H
ereditary ectodermal dysplasia (HED) is characterized by a triad of anomalies, including sweat gland aplasia, hypotrichosis with lanugo, and hypodontia. In addition, dermatographic alterations have been recorded, and frontal bossing wit.h a depressed nasal bridge is commonly enc0untered.l This syndrome complex is usually inherited as an X-linked recessive trait.*, S Recently, PassBarge and Gorlin” and their co-authors have indicated that some cases of HED appear to follow an autosomal mode of transmission; yet, phenotypically, no differences have been encountered between persons manifesting the disease via the two different modes of inheritance. Passarge and associateq4 reported the occurrence of HED in three girls who were the progeny of unaffected parents. They reported that the pedigree indicated numerous instances of consanguinity, including the probands’ parents. They outlined the clinical features of the phenotype but presented no information regarding dental manifestations. For this reason, we are reporting the dental and oral manifestations of the female proband reported by Passarge and co-workers as an autosomal recessive form of HED. *Associate Professor, of Patient Care. **Assistant Professor,
736
Department Department
of Oral of Oral
Diagnosis Pathology.
and Oral
Medicine,
and Coordinator
Hypohidrotic
ectodermal
dysplasia
737
REPORT OF THREE CASES Three young sisters, 7, 10, and 12 years of age, were examined for dental disease in a school-sponsored multiphasic screening program. The dental findings (hypodontia), together with other characteristics similar in each child, established a diagnosis of anhidrotic ectodermal dysplasia and led to an interesting investigation of the genealogy, the highlights of which have been published.4 The complaints, signs and symptoms, and findings in all three patients were essentially the same. During the summer the patients experienced extreme discomfort from the heat and spent much of their time in the waters of a nearby creek in au effort to keep cool. During the winter months they all suffered frequent upper respiratory infections. The parents said: “They choke up and can hardly breathe. They turn blue sometimes while coughing and finally spit up black grisly things.” They were all said to “pass out when they get mad.” the children examined and treated on iilthough psychologic testing was not done, several occasions were mentally alert; they responded to questions and, in general, cornmunicated well with the examiners. V. S., 12 years of age at the time of the examination, weighed 89 pounds and was 54 inches in height. E. S., age 10, was described by the parents as “sickly.” She weighed 46% pounds and was 48J/ inches in height. G. S., age 7, weighed 45 pounds and was 4455 inches in height. The temperature of each child was 98.6’ F. The parents were subjected to the same type of examination as the children and were found to be free of all the aberrant conditions described here. The father weighed 168 pounds and was 66Jh inches in height. The mother weighed 109 pounds and was GOJ/z inches tall. Examination
findings
Fcbcies. The face of each child bore the characteristic features commonly reported to be associated with the syndrome (Fig. l), including a saddle nose or absence of the nasal bridge, everted lips, prominent chin, and frontal bossing. The ears were prominent, and the tragi were vestigial or absent in all three children. Eyes. In all three children the eyes appeared to lack luster, but the parents reported that the rhildren shed tears. There was a whitish discharge of the eyes in each patient. None of the children had eyebrows, and the lashes, though normal in length, were sparse. The wrinkled skin of the eyelids (Fig. 2) appeared to be thin, and there was a marked increase in the palpebral and periorbital pigmentation (Figs. 1 and 2). All of the children complained of photophobia. Respiratory tract. Dryness of the nasal and pharyngeal mucosa was noted in each patient. A dark green phlegmlike material was observed in the pharynx of each child, and the dryness of the mucosa was thought to be responsible for or associated with the hoarseness or laryngitislike speech. There was an irritation of the nasal mucosa in each child. Hair. The hair of the head of each patient was sparse and silky fine in texture. The hair was short, although it had never been cut, and it was evenly distributed (Fig. 1). With the exception of the sparse eyelashes, no other hair could be detected on the body. Slain. The entire body appeared to be extremely dry. The arms and legs were very smooth to touch. The wrists and ankles were extremely rough and tough. The forehead was smooth, but the cheeks were quite rough and scaly. The nipples of each girl were rudimentary, evidenced only by an area of slight pigmentation. Ha&s and feet. Although the cuticle was unkept, the nails of the fingers and toes were and color. In shape, however, the nails well developed. They were normal in size, thickness, were similar to the nails associated with distal phalangeal clubbing seen in patients with congenital heart deformities (Fig. 3). The fingers were prominently tapered (Fig. 4). The palms of the hands, shriveled in appearance, were rough, and the soles of the feet were tough and leathery. Oral findings. There was a characteristic eversion of the lips, and the vermilion borders were poorly defined. The only erupted teeth in each child were the peg-shaped maxillary canines (Fig. 5). Panoramic radiographs revealed three conical impacted teeth in the region of the mandibular symphysis in Patient E. S. (Fig. 6) and one such impaction in the symphysis of
Fig. 1. A and B, Patient V. S., age 12 ; C and D, Patient G . S., age 7. There were striking similarities in the proband. a saddle nose, everted lips, a prominent chin, and frontal in crease in the palpebral and periorbital pigmentation.
E. S., age 10; E and F, P atient Each of the three childre n had bossing. There was :I m arked
Volume Number
33 5
Fig. 8. The eyelashes were sparse, lids were wrinkled in all the patients.
Fig. however, pnt,ients
Hypohidrotic
and there
was a complete
ectodermal
absence
dysplasia
of eyebrows.
739
The
eye-
8. The nails of the fingers and toes were normal in size, thickness, and color. In shape, the nails were similar to the nails associated with distal phnlangeal clubbing seen in with congenital heart deformities.
Patient V. 8. Patient G. 5. had no such impactions. None of the children had lost any teeth. The alveolar ridges were firm and knife edged but extremely low in height, especially in the posterior mandibular areas. Xerostomia was observed in each child, in spite of the fact that milking of the salivary glands produced a scant amount of clenr fluid.
COMMENTS
Congenital absence of teeth is cncounterctl in a. variety of populations and often follows a hereditary pattern. Gl7 In addition, hypodontia may accompany other ectodermal and mesodermal anomalies, including X-linked recessive hypohidrotic ectodermal dysplasia,1-3 autosomal recessive hypohidrotic ectodermal dysplasia,4p5 autosomal dominant dysplasia of nails with hypodontia,8 chondroectodermal dysplasia (Ellis-Van Creveld syndrome) ,g, lo mesoectodermal dysgenesis of iris and cornea with myotonic dystrophy (Rieger’s syndrome),ll premolar dysplasia with premature whitening of hair and palmoplantar hyperhidrosis (B%k’s syndrome) ,I* Marshall’s syndrome,13 and incontinentin pig-
F’iu.
Fig. were
4. The
fingers
were
5. The intraoral findings in each child the peg-shaped maxillary canines.
prominently
were
remarkably
tapered.
similar.
The
only
erupted
teeth
mcnti.14 The patients presented here displayed all of the features usually cncountered in X-linked HED in that thin hair of the lanugo t,ype, hypodontia, and heat intolerance were present in each. In addition, prominent labial protrusion, a depressed nasal bridge, and frontal bossing were present. Gorlin and associates5 have discussed the reported cases of HED occurring in females with regard to possible mechanisms of inheritance. ln affected females the full phenotypic expression of HED, as in the cases reported here, may be the product of an X-linked recessive mode of transmission if the offspring were the product of an affected male and a carrier female. Alternatively, a partial deletion of the noi+mal, paternally derived X-chromosome correspond-
Volume 33 Number 5
Hypohidrotic
ectodermal
dysplasia
741
Fig. 6. Panoramic radiographs revealed three conical teeth in the mandibular symphysis of one of the patients. One of the children had one similar impaction, and the other child had none.
ing to the affected allele on the maternally derived X-chromosome could result in expression of the phenotype in one sibling, but the occurrence of deletion in three members of the sibship is extremely unlikely. The Lyon hypothesis could explain the occurrence of affected females in an X-linked recessive mode of inheritance. The absence of the trait in four generation9 of the kindred reported here, in combination with the prevalence of consanguinity and the finding of three affected females in the proband, are most compatible with an autosomal recessive trait. Since the phenotype in both the X-linked and autosomal recessive forms of HED are clinically identical, it appears that HED can be considered to be genetically heterogeneous. In the casesreported here, the heterozygous parents displayed no manifestations of the trait. Detailed analyses with regard to salivary and sweat gland secretions have not been pursued in these children. Such studies, however, might prove useful in identifying heterozygotes if biochemical differences should be observed. SUMMARY Hereditary ectodermal dysplasia in three sisters has been described. Their pedigree indicated numerous instances of consanguinity, including the parents of the proband. This syndrome complex may be inherited as an X-linked recessive trait, or it may follow an autosomal mode of transmission as in the cases presented here. Regardless of the mode of transmission, however, the phenotypic expressions are the same.
REFERENCES
1. Gorlin, 11. J., and Pindborg, J. J. : Syndromes of the lfentl and Srck, New York, 1964, McGraw-Hill Book Com-Danv. Inc.. UD. 303-311. 2. Franceshetti, A. : Les &spiasies’e%odermiques, Dermatologica 106: 129-156, 1953. 3. McKusick, V. A.: On the X Chromosome of Man, Baltimore, 1964, Waverly Press. 4. Passarge, E., Nuzum, C. T., and Schubert, W. K.: Anhidrotic Ectodermal Dysplasia as Autosomal Recessive Trait in an Inbred Kindred. Humangenetik 3: 181-185, 1966. 5. Gorlin, R. J., Old, T., and Anderson, V. E.: Hypohidrotic Ectodermal Dysplasia in Females: A Critical Analysis and Argument for Genetic Heterogeneity, Z. Kinderheilkcl. 108: l-11, 1970. 6. Woolf, C. M.: Missing Maxillary Lateral Incisors: A Genetic Study, Am. J. Hum. Genet. 23: 289-296, 1971. 7. GrahnBn, H.: Hereditary Factors in Relation to Dental Caries and Congenitally Missing Teeth. In. Witkop, C. J. (editor) : Genetics and Dental Health, New York, 1962, McGrawHill Book Company, Inc., pp. 194-204. 8. Witkop, C. J.: Genetic Disease of the Oral Cavity. In Tiecke, R. W. (editor) : Oral Pathology, New York, 1965, McGraw-Hill Book Company, Inc., p. 812. 9. Ellis, R. W. B., and Van Creveld, 8.: Syndrome Characterized by Ectodermal Dysplasia, Polydactyly, Chondro-Dysplasia and Congenital Morbus Cordis, Arch. Dis. Child. 15: 65-84, 1940. 10. Douglas, W. F., Schonholtz, G. J., and Geppert, L. J.: Chondroectodermal Dysplasia (Ellis-Van Creveld Svndrome) Am. J. Dis. Child. 97: 473-478. 1959. II. hieger, H. : Beitra@ zur genntnis seltenrr Missbildungen ’ der Iris, Graefes Arch. Ophthalmol. 133: 602-635, 1935. 72. Biib;k, J. A.: Clinical and Genetic Studies of Hypodontia. I. Premolar Aplasia, Hyperhidrosis, and Canities Prematura: A New Hereditary Syndrome in Man, Am. J. Hum. Genet. 2: 240-263, 1950. 13. Marshall. D.: Ectodermal DvsDlasia : A Report of Kindred With Ocular Almormnlitic,s and Hearing Defect, Am. J. ~p~hthalmol. 45:&143-156: 1958. 14. Gorlin, R. J., and Anderson, J. A.: The Characterlstie Dentition of Incontinentia Pigmenti (Rloch-Sulzberger Syndrome): A Diagnostic Aid, J. Pediatr. 57: 78-85, 1960. Eeprint
requests
Dr. Richard Department University Lexington,
to :
C. Bartlett of Oral Diagnosis and Oral Medicine of Kentucky College of Dentistry Kp. 40506