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Anhidrotic hereditary ectodermal dysplasia
ANHIDROTIC H E R E D I T A R Y ECTODERMAL DYSPLASIA REPORT OF T w o CASES IN A BROTHER AND SISTER
J. B. SEAGLE, M.D. URBANA, ~LL.
T IS the purpose of this paper to re-
by the writers. A brief review of the American literature diselosed only lings demonstrating the anhidrotic one report of this condition in a retype of hereditary ectodermal dys- male since that time. 4 C h i l d r e n with this syndrome rep]asia. Our interest was attracted to these children by the extreme rarity semble eaeh other due to their unusual fades. This is characterized by of this condition in females. The term " anhi dr ot i c type of he- high prominent brows, saddling of the reditary ectodermal dysplasia" was nasal dorsum, everted lips, retarded introduced by Weech 1 in 1929 because dental development, deformed ears, of the emphasis it placed on the in- and absent or seanty eyebrows and ability to sweat as an important symp- eyelashes. The skin is usually soft tom of this syndrome. The syndrome and dry due to diminished sebaceous is a rare hereditary abnormality, the activity and lack of sweat gland runemost outstanding characteristics of tion. Lanugo hair is absent while which arc anhidrosis or hypohidro- scalp hair is sparse, dry, and brittle. sis, oligodontia or anodontia, and hy- Complete anodontia or delayed dentipotrichosis. The condition is differen- tion and hypodontia of both decidutiated from the more common type of ous and permanent teeth may be preshereditary ectodermal dysplasia ent. The erupted teeth are frequently which is referred to as the hidrotic widely spaced and pointed or pegtype. The latter syndrome does not shaped. Other symptoms which may demonstrate changes in the ability to accompany the condition are atrophic rhinitis, chronic pharyngitis and larsweat or in the sweat glands. Case reports of anhidrotic heredi- yngitis, diminished sense oi taste and t a r y ectodermal dysplasia are rela- smell, decreased function of the lactively rare in the medical literature. rimal glands, absent mammary glands, Upshaw and Montgomery 2 reported in and mental retardation. Heat intolerance due to a generalized absence 1949 that recent reviews of the literature indicated there had been approx- of the sweat glands may be one of the imately eighty cases reported prior to most distressing symptoms noted by 1947. The syndrome occurs most fre- the patient. The body temperature quently in males. Felsher ~ stated in may rise rapidly with strenuous ac1944 that he could find in the litera- tivity, and in the summer these pature only four cases of the anhidrotic tients may become extremely apatype of hereditary ectodermal dys- thetic, fatigued, and may collapse. are plasia in females that had been seen Psychological maladjustments common due to the unusual appearFrom the Department of Pediatrics, Carle ance of these children. Memorial Hospital and Carle Hospital Clinic. 688
I port the case histories of two sib-
SEAGLE:
ANHIDROTIC
HEREDITARY
Most patients displaying this syndrome are thought to represent a Pecessive sex-linked mode of inheritance; however, many differences of opinion have been expressed regarding the type of inheritance involved. On the theory that the great majority of pathological mutations in man are neither fully domi'nant nor fully recessive, Levit ~ explained the inheritance of ectodermal dysplasia as due to conditionally dominant genes with sex linkage. Such genes would show their effect in at least some heterozygous females. Conditions which should be included in the differential diagnosis of hereditary ectodermal dysplasia are congenital syphilis, progeria, hypoparathyroidism, avitaminosis, and fungous infections. The treatment of t h e anhidrotic type of hereditary ectodermal dysplasia is symptomatic. These patients must be taught measures whereby they may avoid hyperthermia in hot weather. Proper care of the skin should be stressed, with emphasis on such measures as the avoidance of the usual soaps and water, the use of one of the superfatted soaps or a soap substitute, and the regular use of some bland oil such as olive oil or cocoa butter to prevent dryness and sealing. Complete dentures should be made for the child as soon as it is possible to gain his cooperation. This may be as early as 3 or 4 years of age. The major psychological adjustments which will be necessary due to the unusual appearance of these children must be anticipated by both the physician and the parents. CASE R E P O R T S
CASE 1.---P. 1K., a white girl, aged 2 years 10 months, was first seen at the Carle Hospital Clinic on Nov. 20,
ECTODERMAL DYSPLASIA
689
1953. This had been the first pregnancy for the 26-year-old mother. The pregnancy, labor, and delivery had been normal. The infant's birth weight had been 7 pounds 1 ounce. Although oxygen and subcutaneous fluids had been given to the infant during the first two days of life, the mother stated t hat she had seemed normal during the neonatal period except for dryness of the skin and puffiness of the eyes. The infant had been breast fed for the first six weeks of life, and a multiple vitamin preparation had been given daily after the first month. Although the patient had always been offered an adequate diet and had eaten well, she had gained weight slower than expected and had always seemed to be small. The infant was said to have rolled over well at 6 months and to have sat alone at 7 months. She had walked without help at 111/2 months. Her first words had been spoken at 12 months, although she said only six words at 21/2 years. Her first and only tooth had erupted at 15 months. She had been toilet trained by 2 years. She was extremely active and showed interest in the usual activities of children of comparable age. The parents stated that the child's hair had always been very sparse, dry, and fine. They had seen neither eyelashes nor eyebrows. Her one tooth had always been pointed. Perspiration had never been noted on any part of her body, even in hot weather. Her only previous illnesses had been rubella and the usual childhood upper respiratory infections. However, it had been noted t hat she usually developed a rectal temperature of 104 ~ to 105 ~ F. with each upper respiratory infection. In hot weather she often was extremely irritable and apprehensive. The parents had learned that frequent cooling baths made her more comfortable during warm weather. She also suffered frequent cracking of the skin o4 the eubital and popliteal fossae. There was no history o~ consanguinity in the parents. The family history was essentially negative. How-
690
THE
J O U R N A L OF P E D I A T R I C S
ever, the mother of these children stated that many of her deciduous and permanent teeth had been missing and that some of those which had been present had been pointed. She had had complete dentures made at 14 years of age. The mother stated that
and activities were normal for her chronological age. The blood pressure was 92/60. She had very sparse, dry, blond hair on her scalp. Eyebrows were absent and eyelashes were fine and sparse. Lanugo hair was absent. The skin was soft and dry, and no
A.
B.
F i g . 1 . - - A , P a m e l a , a g e d 2 y e a r s 10 m o n t h s ; B, S t e v e n , a g e d I y e a r 5 m o n t h s . Note t h e t h i n h a i r a n d a b s e n t e y e b r o w s . T h e s p a r s e e y e l a s h e s a r e n o t v i s i b l e h e r e . E v e r t e d lips a n d pointed deciduous teeth m a y he seen.
she had always had a dry skin and that her hair had been sparse until about 14 years of age. She had no eyelashes during childhood. Her eyelashes, axillary and pubic hair are still quite sparse. She also stated that she had very little perspiration even during hot weather. The mother's two siblings and parents were said to be completely normal individuals. Physical Examination.---The patient was a frail-appearing, pate white girl. She weighed 25 pounds and was 35 inches tall. Her muscle coordination
perspiration was noted even after moderate activity. There was a slight depression of the d0rsum of the nose. The only tooth present was a pointed, deciduous, right maxillary cuspid. Examination of the external eyes and fundi was normal. Examination of the nails, pharynx, neck, heart, lungs, abdomen, and genitals was essentially negative. Neurological examination ~raS norI~lal.
Laboratory Examinations.--A complete blood count revealed the hemoglobin to be 10.6 grams; red blood cell count, 3,400,000; and white blood
SEAGLE:
ANHIDROTIC HEREDITARY ECTODERMAL DYSPLASIA
cells, ]1,300 with 46 per cent neutrophils, 44 per cent lymphocytes, 6 per cent monocytes, 2 per cent eosinophils, and 2 per cent basophils. The urinalysis disclosed a specific gravity of 1.012; albumin and sugar were absent, and the microscopic examination of the urine was negative. Serum calcium was 9.4 rag. per 100 c.c.; ser u m phosphorus, 5.0 rag. per 100 c.c. ; plasma cholesterol, 220 rag. per 100 c.c. Chest x - r a y was negative. X-rays of the wrists showed two centers of ossification. CASE 2.--S. ~V[., 17-month-old white male infant, was first seen at the Carle Hospital Clinic on Nov. 20, 1953. The m o t h e r ' s prenatal history, labor, and delivery had been normal. The inf a n t ' s birth weight had been 5 pounds 14 ounces. His parents had felt t h a t he looked " j u s t like his s i s t e r " at the time of birth. He had had no illnesses d u r i n g the neonatal period. He had been breast fed for two months and had received a normal i n f a n t diet with vitamin supplements. His development had been normal except for slowness of dentition. The first deciduous tooth had a p p e a r e d at 12 months and had been followed b y a second at 16 months. Both of these teeth were pointed. His only illnesses had been tonsillitis associated with u p p e r r e s p i r a t o r y infections on three occasions. Mild u p p e r r e s p i r a t o r y infections had usually been accompanied by high fever. The parents had noted the same characteristics of the hair and skin which t h e y had observed in their older child. T h e y could not r e m e m b e r having seen perspiration on his skin d u r i n g hot weather. E x t r e m e irritability and apprehension were noted whenever he became overheated. Physical E x a m i n a t i o n . - - T h i s male infant weighed 221~ pounds and was 311~ inches tall. He appeared well nourished. The anterior ~ontanel was closed. Blood pressure was not obtained. The hair on the scalp was sparse and dry. E y e b r o w s were absent and eyelashes were fine and v e r y
691
sparse. The skin was pale and dry, no perspiration being noted even dur~ ing crying. There were two pointed cuspids present. The tonsils were m o d e r a t e l y enlarged and ragged. He walked well and was e x t r e m e l y active. E x a m i n a t i o n of the eyes, nails, nose, neck, heart, lungs, abdomen, and genitals was negative. Neurological examination was negative. Laboratory
E x a m i n a t i o n s . - C o re-
plete blood count showed the hemoglobin to be 7.8 grams; red blood cell count, 3,700,000; and white blood cell count, 6,500 with a differential count revealing 27 per cent neutrophils, 59 per cent lymphocytes, 5 per cent monocytes, 7 per cent eosinophils, and 2 per cent basophils. Mild hypochromia and anisocytosis were noted on the blood smear. The urinalysis was completely negative. The Kline and K a h n reactions were negative. The plasma cholesterol was 170 rag. per ]00 c.c. X - r a y of the chest showed some accentuation of the bronchovascular markings bilaterally. X-rays of both wrists showed one ossification center. SUMMARY
The case reports of a brother and sister with the anhidrotic type of her e d i t a r y ectodermal dysplasia have been presented. REFERENCES 1. Weech, A. A.: H e r e d i t a r y Ectodermal Dysplasia (Congenital E c t o d e r m a l Def e c t ) : A l~eport of Two Cases, Am. J. Dis. Child. 37: 766, 1929. 2. Upshaw, B e t t e u and Montgomery, Hamilton: t t e r e d i t a r y A n h i d r o t i c Ectodermal Dysplasia, Arch. Dermat. & Syph. 60: 1170, 1949. 3. Felsher, Zachary: H e r e d i t a r y Ectodermal D y s p l a s i a - - R e p o r t of a Case W i t h E x p e r i m e n t a l Study, Arch. Dermat. & Syph. 49: 410~ 1944. 4. E v e r e t t , F r a n k G., Jump, Ellis B., Suther]and, Wallace F., Savara, Bhim Sen, and Suher, Theodore: A n h i d r o t i c Ectodermal Dysplasia W i t h A n o d o n t i a : A Study of Two Families, J. Am. Dent. A. 44: 173, 1952. 5. Levit, S . G . : The P r o b l e m of Dominance in Man, J. Genet. 33: 411, 1936.
J. B. SEAGLE, M.D. URBANA, ~LL.
T IS the purpose of this paper to re-
by the writers. A brief review of the American literature diselosed only lings demonstrating the anhidrotic one report of this condition in a retype of hereditary ectodermal dys- male since that time. 4 C h i l d r e n with this syndrome rep]asia. Our interest was attracted to these children by the extreme rarity semble eaeh other due to their unusual fades. This is characterized by of this condition in females. The term " anhi dr ot i c type of he- high prominent brows, saddling of the reditary ectodermal dysplasia" was nasal dorsum, everted lips, retarded introduced by Weech 1 in 1929 because dental development, deformed ears, of the emphasis it placed on the in- and absent or seanty eyebrows and ability to sweat as an important symp- eyelashes. The skin is usually soft tom of this syndrome. The syndrome and dry due to diminished sebaceous is a rare hereditary abnormality, the activity and lack of sweat gland runemost outstanding characteristics of tion. Lanugo hair is absent while which arc anhidrosis or hypohidro- scalp hair is sparse, dry, and brittle. sis, oligodontia or anodontia, and hy- Complete anodontia or delayed dentipotrichosis. The condition is differen- tion and hypodontia of both decidutiated from the more common type of ous and permanent teeth may be preshereditary ectodermal dysplasia ent. The erupted teeth are frequently which is referred to as the hidrotic widely spaced and pointed or pegtype. The latter syndrome does not shaped. Other symptoms which may demonstrate changes in the ability to accompany the condition are atrophic rhinitis, chronic pharyngitis and larsweat or in the sweat glands. Case reports of anhidrotic heredi- yngitis, diminished sense oi taste and t a r y ectodermal dysplasia are rela- smell, decreased function of the lactively rare in the medical literature. rimal glands, absent mammary glands, Upshaw and Montgomery 2 reported in and mental retardation. Heat intolerance due to a generalized absence 1949 that recent reviews of the literature indicated there had been approx- of the sweat glands may be one of the imately eighty cases reported prior to most distressing symptoms noted by 1947. The syndrome occurs most fre- the patient. The body temperature quently in males. Felsher ~ stated in may rise rapidly with strenuous ac1944 that he could find in the litera- tivity, and in the summer these pature only four cases of the anhidrotic tients may become extremely apatype of hereditary ectodermal dys- thetic, fatigued, and may collapse. are plasia in females that had been seen Psychological maladjustments common due to the unusual appearFrom the Department of Pediatrics, Carle ance of these children. Memorial Hospital and Carle Hospital Clinic. 688
I port the case histories of two sib-
SEAGLE:
ANHIDROTIC
HEREDITARY
Most patients displaying this syndrome are thought to represent a Pecessive sex-linked mode of inheritance; however, many differences of opinion have been expressed regarding the type of inheritance involved. On the theory that the great majority of pathological mutations in man are neither fully domi'nant nor fully recessive, Levit ~ explained the inheritance of ectodermal dysplasia as due to conditionally dominant genes with sex linkage. Such genes would show their effect in at least some heterozygous females. Conditions which should be included in the differential diagnosis of hereditary ectodermal dysplasia are congenital syphilis, progeria, hypoparathyroidism, avitaminosis, and fungous infections. The treatment of t h e anhidrotic type of hereditary ectodermal dysplasia is symptomatic. These patients must be taught measures whereby they may avoid hyperthermia in hot weather. Proper care of the skin should be stressed, with emphasis on such measures as the avoidance of the usual soaps and water, the use of one of the superfatted soaps or a soap substitute, and the regular use of some bland oil such as olive oil or cocoa butter to prevent dryness and sealing. Complete dentures should be made for the child as soon as it is possible to gain his cooperation. This may be as early as 3 or 4 years of age. The major psychological adjustments which will be necessary due to the unusual appearance of these children must be anticipated by both the physician and the parents. CASE R E P O R T S
CASE 1.---P. 1K., a white girl, aged 2 years 10 months, was first seen at the Carle Hospital Clinic on Nov. 20,
ECTODERMAL DYSPLASIA
689
1953. This had been the first pregnancy for the 26-year-old mother. The pregnancy, labor, and delivery had been normal. The infant's birth weight had been 7 pounds 1 ounce. Although oxygen and subcutaneous fluids had been given to the infant during the first two days of life, the mother stated t hat she had seemed normal during the neonatal period except for dryness of the skin and puffiness of the eyes. The infant had been breast fed for the first six weeks of life, and a multiple vitamin preparation had been given daily after the first month. Although the patient had always been offered an adequate diet and had eaten well, she had gained weight slower than expected and had always seemed to be small. The infant was said to have rolled over well at 6 months and to have sat alone at 7 months. She had walked without help at 111/2 months. Her first words had been spoken at 12 months, although she said only six words at 21/2 years. Her first and only tooth had erupted at 15 months. She had been toilet trained by 2 years. She was extremely active and showed interest in the usual activities of children of comparable age. The parents stated that the child's hair had always been very sparse, dry, and fine. They had seen neither eyelashes nor eyebrows. Her one tooth had always been pointed. Perspiration had never been noted on any part of her body, even in hot weather. Her only previous illnesses had been rubella and the usual childhood upper respiratory infections. However, it had been noted t hat she usually developed a rectal temperature of 104 ~ to 105 ~ F. with each upper respiratory infection. In hot weather she often was extremely irritable and apprehensive. The parents had learned that frequent cooling baths made her more comfortable during warm weather. She also suffered frequent cracking of the skin o4 the eubital and popliteal fossae. There was no history o~ consanguinity in the parents. The family history was essentially negative. How-
690
THE
J O U R N A L OF P E D I A T R I C S
ever, the mother of these children stated that many of her deciduous and permanent teeth had been missing and that some of those which had been present had been pointed. She had had complete dentures made at 14 years of age. The mother stated that
and activities were normal for her chronological age. The blood pressure was 92/60. She had very sparse, dry, blond hair on her scalp. Eyebrows were absent and eyelashes were fine and sparse. Lanugo hair was absent. The skin was soft and dry, and no
A.
B.
F i g . 1 . - - A , P a m e l a , a g e d 2 y e a r s 10 m o n t h s ; B, S t e v e n , a g e d I y e a r 5 m o n t h s . Note t h e t h i n h a i r a n d a b s e n t e y e b r o w s . T h e s p a r s e e y e l a s h e s a r e n o t v i s i b l e h e r e . E v e r t e d lips a n d pointed deciduous teeth m a y he seen.
she had always had a dry skin and that her hair had been sparse until about 14 years of age. She had no eyelashes during childhood. Her eyelashes, axillary and pubic hair are still quite sparse. She also stated that she had very little perspiration even during hot weather. The mother's two siblings and parents were said to be completely normal individuals. Physical Examination.---The patient was a frail-appearing, pate white girl. She weighed 25 pounds and was 35 inches tall. Her muscle coordination
perspiration was noted even after moderate activity. There was a slight depression of the d0rsum of the nose. The only tooth present was a pointed, deciduous, right maxillary cuspid. Examination of the external eyes and fundi was normal. Examination of the nails, pharynx, neck, heart, lungs, abdomen, and genitals was essentially negative. Neurological examination ~raS norI~lal.
Laboratory Examinations.--A complete blood count revealed the hemoglobin to be 10.6 grams; red blood cell count, 3,400,000; and white blood
SEAGLE:
ANHIDROTIC HEREDITARY ECTODERMAL DYSPLASIA
cells, ]1,300 with 46 per cent neutrophils, 44 per cent lymphocytes, 6 per cent monocytes, 2 per cent eosinophils, and 2 per cent basophils. The urinalysis disclosed a specific gravity of 1.012; albumin and sugar were absent, and the microscopic examination of the urine was negative. Serum calcium was 9.4 rag. per 100 c.c.; ser u m phosphorus, 5.0 rag. per 100 c.c. ; plasma cholesterol, 220 rag. per 100 c.c. Chest x - r a y was negative. X-rays of the wrists showed two centers of ossification. CASE 2.--S. ~V[., 17-month-old white male infant, was first seen at the Carle Hospital Clinic on Nov. 20, 1953. The m o t h e r ' s prenatal history, labor, and delivery had been normal. The inf a n t ' s birth weight had been 5 pounds 14 ounces. His parents had felt t h a t he looked " j u s t like his s i s t e r " at the time of birth. He had had no illnesses d u r i n g the neonatal period. He had been breast fed for two months and had received a normal i n f a n t diet with vitamin supplements. His development had been normal except for slowness of dentition. The first deciduous tooth had a p p e a r e d at 12 months and had been followed b y a second at 16 months. Both of these teeth were pointed. His only illnesses had been tonsillitis associated with u p p e r r e s p i r a t o r y infections on three occasions. Mild u p p e r r e s p i r a t o r y infections had usually been accompanied by high fever. The parents had noted the same characteristics of the hair and skin which t h e y had observed in their older child. T h e y could not r e m e m b e r having seen perspiration on his skin d u r i n g hot weather. E x t r e m e irritability and apprehension were noted whenever he became overheated. Physical E x a m i n a t i o n . - - T h i s male infant weighed 221~ pounds and was 311~ inches tall. He appeared well nourished. The anterior ~ontanel was closed. Blood pressure was not obtained. The hair on the scalp was sparse and dry. E y e b r o w s were absent and eyelashes were fine and v e r y
691
sparse. The skin was pale and dry, no perspiration being noted even dur~ ing crying. There were two pointed cuspids present. The tonsils were m o d e r a t e l y enlarged and ragged. He walked well and was e x t r e m e l y active. E x a m i n a t i o n of the eyes, nails, nose, neck, heart, lungs, abdomen, and genitals was negative. Neurological examination was negative. Laboratory
E x a m i n a t i o n s . - C o re-
plete blood count showed the hemoglobin to be 7.8 grams; red blood cell count, 3,700,000; and white blood cell count, 6,500 with a differential count revealing 27 per cent neutrophils, 59 per cent lymphocytes, 5 per cent monocytes, 7 per cent eosinophils, and 2 per cent basophils. Mild hypochromia and anisocytosis were noted on the blood smear. The urinalysis was completely negative. The Kline and K a h n reactions were negative. The plasma cholesterol was 170 rag. per ]00 c.c. X - r a y of the chest showed some accentuation of the bronchovascular markings bilaterally. X-rays of both wrists showed one ossification center. SUMMARY
The case reports of a brother and sister with the anhidrotic type of her e d i t a r y ectodermal dysplasia have been presented. REFERENCES 1. Weech, A. A.: H e r e d i t a r y Ectodermal Dysplasia (Congenital E c t o d e r m a l Def e c t ) : A l~eport of Two Cases, Am. J. Dis. Child. 37: 766, 1929. 2. Upshaw, B e t t e u and Montgomery, Hamilton: t t e r e d i t a r y A n h i d r o t i c Ectodermal Dysplasia, Arch. Dermat. & Syph. 60: 1170, 1949. 3. Felsher, Zachary: H e r e d i t a r y Ectodermal D y s p l a s i a - - R e p o r t of a Case W i t h E x p e r i m e n t a l Study, Arch. Dermat. & Syph. 49: 410~ 1944. 4. E v e r e t t , F r a n k G., Jump, Ellis B., Suther]and, Wallace F., Savara, Bhim Sen, and Suher, Theodore: A n h i d r o t i c Ectodermal Dysplasia W i t h A n o d o n t i a : A Study of Two Families, J. Am. Dent. A. 44: 173, 1952. 5. Levit, S . G . : The P r o b l e m of Dominance in Man, J. Genet. 33: 411, 1936.