American Journal of M e d i c a l Genetics 44:158-162 (1992)
Brief Clinical Report
Autosomal Recessive Cleft Lip/Palate, Ectodermal Dysplasia, and Minor Acral Anomalies: Report of a Brazilian Family Antonio Richieri-Costa, Maria k i n e Guion-Almeida, Newton fieire-Maia, and Marta Pinheiro Servko de Gene'tica Clinica, Hospital de Pesquisa e Reabilitach de LesBes Labw-Palatais, Universidade de Scio Paulo, Bauru, SP, Brazil (A.R.-C.,M.L.G.-A.),and Departamento de Gene'tica, Universidade Federal do Parand, Curitiba, PR, Brazil ( M P . , N.F.-M,) We report on a Brazilian woman, born to consanguineous (first cousin) parents (F = 1/16) and presenting cleft lip/palate, ectodermal dysplasia, interdigital webbing, and other malformations. Parental consanguinity and possible recurrence in sibs suggest autosoma1 recessive inheritance. The nosologic aspects with the Martinez syndrome and with the Zlotogora-Ogur syndrome are discussed.
CLINICAL REPORT DMM (Fig. 11,the proposita 23 years old (IV-9;Fig. 21, was born in the State of Minas Gerais, Brazil, to a 30year-old G9P8A1 mother and her first cousin, 36-yearold husband. The family has a remote Portuguese origin. The pregnancy was normal. There was absence of trauma or exposure to toxic or infectious agents or to X-rays. Normal, term delivery. Birth measurements were not recorded. Bilateral cleft lip/palate was noted at 0 1992 Wiley-Liss, Inc. birth. There was normal neuropsychological development. Ureteral stenosis was repaired at age 5 years. The KEY WORDS: cleft liplpalate, ectodermal outcomes of previous pregnancies were (1)three childysplasia, digital webbing, dren with bilateral cleft liplpalate (IV-3, IV-4, and Martinez syndrome, ZlotoIV-61,who died neonatally; (2) four normal and married gora-Ogur syndrome, autosons (IV-1,IV-5, IV-7, and IV-8),and (3) a first trimester soma1 recessive inheritance abortion (IV-2). Two relatives through the father's mother line had cleft lip (111-1) and cleft lip/palate (111-2). INTRODUCTION Clinical examination at age 22 years: height 160 cm (25th-50th centile), weight 50 kg (10th-25th centile), Ectodermal dysplasia (ED), cleft lip/palate (CUP), and limb anomalies have been reported as component manifestations of several conditions [Rosselli and Gulienetti, 1961; Freire-Maia, 1970; Bowen and Armstrong, 1976; Michels et al., 1978; Martinez et al., 1987; Zlotogora et al., 1987; Ogur and Yuksel, 1988; Rodini and Richieri-Costa, 1990a,b]. This paper describes a girl with an apparently new autosomal recessive syndrome which combines CL/P and ED of the subgroup 1-2-4, according to Freire-Maia's [1971, 19771 classification. When we consider the cluster of anomalies of the present patient and its cause, only 2 of the above mentioned conditions should be considered in the differential diagnosis, namely, the Zlotogora-Ogur and the Martinez syndromes. Received for publication September 4, 1991; revision received March 9, 1992. Address reprints request t o Dr. N. Freire-Maia, Departamento de Genbtica, UFPR, Caixa Postal 19071, 81531 Curitiba, PR, Brazil.
0 1992 Wiley-Liss, Inc.
Fig. 1. The proposita at age 23 years. For details, see text.
CLP/Ectodermal Dysplasia/Acral Anomalies
159
I
II
Ill
1
IV
V
Fig. 2. Pedigree of the family. 6 cleft lip; B cleft palate; 0 affected with the syndrome.
toe 5 (Fig. 4) with marked hypoplasia of the toenail, and lumbar lordosis. Dermatoglyphics showed hypoplastic lines, and the digital patterns were W, L", Wd, Wd, and L" at right, and L", W, W, W, and L" at left. Ophthalmologic and hearing evaluation were normal. Sweat pore studies of the hypothenar region (direct counting, and in alginate and polyvinyl glue impression) showed decreased number of palmar creases, sparce and small pores (mean of 6 pores/cm2).Results of routine laboratory blood tests were normal. Orthopantomographies performed at 13 and 23 years (Fig. 5) showed delayed dental development, with persistence of deciduous teeth, mesiodens, oligodontia, and microdontia. The missing permanent teeth according to the Palmer dental classification were
5 212 8 7 5 I
8
5 5
78 8
Roentgenograms of the appendicular skeleton showed bilateral camptodactyly of toe 4, and mild hypoplasia of toe 5, signs already seen by clinical examination. SEM analysis of hair shafts revealed different structural changes (Fig. 6 ) . DISCUSSION The ectodermal dysplasia subgroup 1-2-4 of FreireMaia's classification [1971, 19771now consists of 8 con-
Fig. 3. The hands of the proposita. For details, see text.
OFC 53 cm (25th-50th centile), inner canthal distance 3.5 cm (75th-97th centile), outer canthal distance 9.5 cm (75th-97th centile), and interpupillary distance 6.0 cm (75th-97th centile). She had high forehead, arched and dysplastic eyebrows (highly hypotrichotic at their lateral halves), hypoplastic lacrimal puncta, broad nose (including nose bridge), hypoplastic nasal alae, bilateral scars resulting from bilateral cleft lip/palate correction, sparse, coarse and straight hair, dry skin, hypohidrosis without hyperthermia (by history), marked proximal interdigital webbing between fingers 2-3-4 (Fig. 3), bilateral camptodactyly of toe 4 and hypoplastic
Fig. 4. The feet of the proposita. For details, see text.
160
Richiei-Costa et al. [Zlotogora et al., 1987; Ogur and Yuksel, 1988; Zlotogora and Ogur, 1988; Fbdini and Richieri-Costa, 1990b1, and the other of the subgroup 1-2, the Martinez syndrome [Martinez et al., 19871, share some signs with the patient here described, namely, trichodysplasia, dental defects, dyshidrosis, and dysplastic skin anomalies, among other signs (Table I). The main differential signs present in the Zlotogora-Ogur syndrome include mental retardation, as well as nipple and ear anomalies which are absent in our patient. Our patient resembles the Martinez syndrome, however, differing with respect to many signs (Table I). Another equally important difference is the pattern of inheritance, presumably autosomal dominant in the Martinez syndrome, and probably autosomal recessive in the present family. Taking into account these differences, we would like to suggest that the present condition is an apparently hitherto undescribed “new” syndrome. A final comment seems to be necessary. Note that in the inbred sibship under investigation, 3 apparently affected sibs (IV-3, IV-4, and IV-6) only had bilateral cleft liplpalate as the proposita (IV-9) who also had a number of other signs. Since there are, in the same family, 2 other cases of lip/palate clefts (111-1and 111-21, it is possible to develop the following hypotheses:
Fig. 5. Orthopantomograms performed at ages 13years (above) and 23 (below). For details, see text.
ditions: the F6ra syndrome (regional ectodermal dysplasia with total bilateral cleft), Berlin syndrome (leucomelanoderma), Book dysplasia, congenital insensitivity to pain with anhidrosis of Swanson, Lenz-Passarge dysplasia, Wesser-Vistnes ectodermal dysplasia with palatal paralysis, Johnson neuroectodermal syndrome [Johnson et al., 19831, and hypohidrotic ectodermal dysplasia with focal sweating [Gorlin, 19881 [for the first 6 conditions, see Freire-Maia and Pinheiro, 19841. Cleft lip/palate and isolated cleft palate have been reported in the Fara syndrome and in the Johnson neuroectodermal syndrome, respectively, but the whole clinical picture of these conditions clearly distinguish them from the present one. Ectodermal dysplasia sensu lato, cleft lip/palate, and limb anomalies are part of some well known syndromes [Rapp and Hodgkin, 1968; Rosselli and Gulienetti, 1961; Freire-Maia, 1970; Bowen and Armstrong, 1976; Hay and Wells, 1976; Allanson and McGillivray, 1985; Rodini et al., 1990; Rodini and Richieri-Costa 1990aI. The phenotype of the patient here described prompts a clear distinction with all the above mentioned conditions. Two of the conditions with CL/P and ED, one of the subgroup 1-2-3-4, the Zlotogora-Ogur syndrome
1. There are 6 persons (111-1, 111-2, IV-3, IV-4, IV-6, and IV-9) affected with cleft lip/palate. The proposita (IV-9), besides the lip/palate malformation, also presents by coincidence (“concurrence”)a syndrome characterized by the other signs presented in Table I. This hypothesis seems to be rather improbable since a high recurrence risk is not generally expected in lip/palate clefts. 2. At least one or %and possibly all 3 sibs-would have had the syndrome if they had survived early infancy. With this hypothesis, the segregation rate would be 418. By eliminating the proposita, the corrected segregation rate would turn out to be 3/7, which does not depart significantly from the expected 114 ratio (p= 1.19;P > 0.20, one degree of freedom). The same is true with respect to the most conservative hypothesis (only one sib with the condition):corrected segregation rate of 1/7; p = 0.43; P > 0.50.
ACKNOWLEDGMENTS The authors gratefully acknowledge the assistance of Miss Alba Regina Turin (Instituto de Tecnologia do Paranti) for the SEM photographs of the hair shafts of the proposita, and the CNPq for grants to the research projects of the group from the UFPR. M.P. and N.F.-M. are research fellows of CNPq. REFERENCES Allanson JE, McGillivray BC (1985):Familial clefting syndrome with ectropion and dental anomaly without limb anomalies. Clin Genet 27:426-429. Bowen P, Armstrong HB (1976): Ectodermal dysplasia, mental retardation, cleft lip/palate and other anomalies in three sibs. Clin Genet 935-42. Freire-Maia N (1970): A newly recognized genetic syndrome of tetramelic deficiencies, ectodermal dysplasia, deformed ears, and other abnormalities. Am J Hum Genet-22:370-377.
CLP/Ectodermal DysplasidAcral Anomalies
161
Fig. 6. SEM analysis of hair shafts of the proposita showing different longitudinal grooves.
Freire-MaiaN (1971): Ectodermal dysplasias. HumHered 21:309-312. Freire-Maia N (1977): Ectodermal dysplasias revisited. Acta Genet Med Gemellol 26:121-131. Freire-Maia N, Pinheiro M (1984): “Ectodermal Dysplasias: A Clinical and Genetic Study.” New York Alan R Liss. Gorlin RJ (1988): Selected ectodermal dysplasias. In Salinas CF, Opitz JM, Paul NW (eds): “Recent Advances in Ectodermal Dysplasias.” New York: Alan R. Liss, for the National Foundation-March of Dimes. BD:OAS XXIV (2):123-148. Hay RJ,Wells RS (1976): The syndrome of ankyloblepharon, ectoderma1 defects and cleft lip/palate: An autosomal dominant condition. Br J Dermatol 94:277-289. Johnson VP, McMillin JM, Aceto T, Jr, Bruins G (1983): A newly recognized neuroectodermal syndrome of familial alopecia, anosmia, deafness, and hypogonadism. Am J Med Genet 15:497-506. Martinez RB, Monasterio LA, Pinheiro M, Freire-Maia N (1987): Cleft lip/palate-oligodontia-syndactyly-hairalterations, a new syndrome: Review of the conditions combining ectodermal dysplasia and cleft liplpalate. Am J Med Genet 27:23-31. Michels VV, Hiltner HN, Beaudet AL (1978): A clefting syndrome with ocular anterior chamber defect and lid anomalies. J Pediatr 93:443-446.
Ogur G, Yuksel M (1988): Association of syndactyly, ectodermal dysplasia, and cleft lip and palate: report of two sibs from Turkey. J Med Genet 25:37-40. Rapp RS, Hodgkin WE (1968): Anhidrotic ectodermal dysplasia: Autosoma1 dominant inheritance with palate and lip anomalies. J Med Genet 5:269-272. Rodini ESO, likeitas JAS, Richieri-Costa A (1990).Rapp-Hodgkin syndrome: Report of a Brazilian family. Am J Med Genet 36:463-466. Rodini ESO, Richieri-Costa A (1990a): EEC syndrome: Report on 20 new patients, clinical and genetic considerations. Am J Med Genet 37:42-53. M i n i ESO, Rchieri-Costa A (1990b):Autosomal recessive ectodermal dysplasia, cleft lipipalate, mental retardation, and syndactyly: The Zlotogora-Ogur syndrome. Am J Med Genet 36:473-476. Rosselli D, Gulienetti R (1961):Edodermal dysplasia. Br J Plast Surg 14:190-204. Zlotogora J , Ogur G (1988): Syndactyly, ectodermal dysplasia, and cleft lip and palate. J Med Genet 25503. Zlotogora J, Zilberman Y, Tenenbaum A, Wexler MR (1987): Cleft lip and palate, pili torti, malformed ears, partial syndactyly of fingers and toes, and mental retardation: A new syndrome? J Med Genet 24:291-293.
162
Richiei-Costa et al.
TABLE I. Comparison Among Previously Described Similar Patients and the Present One Zlotogora-Ogur Syndromea Martinez syndrome Ogur and Rodini and Zlotogora et al. Yuksel Richieri-Costa Martinez et al. [19871 [19881 [1990b] [19871 1 1 1 1 Number of families + + Consanguineous parents + 2 2 5 1 Number of cases F M M 2 M b M M M F M SeX 8y 5,14,16y 4Y 4Y t8m 1Oy Age Craniofacial signs B L B B B B B L B Cleft lip + + + + + + + + + Cleft palate N R - - + Midface hypoplasia Brachycephaly N R + - + Prominent forehead + ? + + N R + + + + Micrognathia + + N R - - + + + N R + + + + Abnormal dentition + NR N R - - + Ocular hypertelorism Prominent eyes N R - - + Nose anomalies + + N R + + + + Abnormal ears + + + + N R + + + + Hair changes + + + + N R + + + Sparse scalp hair ? ? N R ? ? ? +Structural changes + + + + N R + + + Hypotrichotic eyebrows +NR N R - - + Two hair whorls Skin N R - - + + SimiadSydney line + + N R + + + Thick and/or dry skin + + ? + + N R + + + Abnormal nipples/areolae + + N R + + + Hypohidrosis Neuropsychological + NR + + N R + + + Mental retardation NR + + N R + + + Psychomotor retardation Limbs + + ++- Nm R -+ + + +Syndactyly Camptodactyly N R - - Hypoplastic 5th toes Other findings + + N R - - GU anomalies + NR N R - - NR Hypoplastic lacrimal puncta + N R - - Vertebral anomalies Inheritance AR AR AR AD?,AR?,XD?' "See also Zlotogora and Ogur [19881. bNeonatal death; M, male; F, female; B, bilateral; L, left; NR, not recorded since the children died very young. 'The mother of the proposita has a few mild clinical signs.
Present case 1
+
4? 1Mb,F,2Fb 23Y B
+
NR NR NR NR NR NR NR NR NR
B
B
-
NR NR NR
+ + + NR NR + NR NR + NR -
+
- N R
NR NR NR NR
+ +
NR NR NR NR
-
NR NR NR NR
-
NR NR
NR NR
+
-
+ + -
NR NR NR NR
NR NR NR
+ N R + N R
+
NR
NR NR NR
+ + +
NR NR NR
AR
Brief Clinical Report
Autosomal Recessive Cleft Lip/Palate, Ectodermal Dysplasia, and Minor Acral Anomalies: Report of a Brazilian Family Antonio Richieri-Costa, Maria k i n e Guion-Almeida, Newton fieire-Maia, and Marta Pinheiro Servko de Gene'tica Clinica, Hospital de Pesquisa e Reabilitach de LesBes Labw-Palatais, Universidade de Scio Paulo, Bauru, SP, Brazil (A.R.-C.,M.L.G.-A.),and Departamento de Gene'tica, Universidade Federal do Parand, Curitiba, PR, Brazil ( M P . , N.F.-M,) We report on a Brazilian woman, born to consanguineous (first cousin) parents (F = 1/16) and presenting cleft lip/palate, ectodermal dysplasia, interdigital webbing, and other malformations. Parental consanguinity and possible recurrence in sibs suggest autosoma1 recessive inheritance. The nosologic aspects with the Martinez syndrome and with the Zlotogora-Ogur syndrome are discussed.
CLINICAL REPORT DMM (Fig. 11,the proposita 23 years old (IV-9;Fig. 21, was born in the State of Minas Gerais, Brazil, to a 30year-old G9P8A1 mother and her first cousin, 36-yearold husband. The family has a remote Portuguese origin. The pregnancy was normal. There was absence of trauma or exposure to toxic or infectious agents or to X-rays. Normal, term delivery. Birth measurements were not recorded. Bilateral cleft lip/palate was noted at 0 1992 Wiley-Liss, Inc. birth. There was normal neuropsychological development. Ureteral stenosis was repaired at age 5 years. The KEY WORDS: cleft liplpalate, ectodermal outcomes of previous pregnancies were (1)three childysplasia, digital webbing, dren with bilateral cleft liplpalate (IV-3, IV-4, and Martinez syndrome, ZlotoIV-61,who died neonatally; (2) four normal and married gora-Ogur syndrome, autosons (IV-1,IV-5, IV-7, and IV-8),and (3) a first trimester soma1 recessive inheritance abortion (IV-2). Two relatives through the father's mother line had cleft lip (111-1) and cleft lip/palate (111-2). INTRODUCTION Clinical examination at age 22 years: height 160 cm (25th-50th centile), weight 50 kg (10th-25th centile), Ectodermal dysplasia (ED), cleft lip/palate (CUP), and limb anomalies have been reported as component manifestations of several conditions [Rosselli and Gulienetti, 1961; Freire-Maia, 1970; Bowen and Armstrong, 1976; Michels et al., 1978; Martinez et al., 1987; Zlotogora et al., 1987; Ogur and Yuksel, 1988; Rodini and Richieri-Costa, 1990a,b]. This paper describes a girl with an apparently new autosomal recessive syndrome which combines CL/P and ED of the subgroup 1-2-4, according to Freire-Maia's [1971, 19771 classification. When we consider the cluster of anomalies of the present patient and its cause, only 2 of the above mentioned conditions should be considered in the differential diagnosis, namely, the Zlotogora-Ogur and the Martinez syndromes. Received for publication September 4, 1991; revision received March 9, 1992. Address reprints request t o Dr. N. Freire-Maia, Departamento de Genbtica, UFPR, Caixa Postal 19071, 81531 Curitiba, PR, Brazil.
0 1992 Wiley-Liss, Inc.
Fig. 1. The proposita at age 23 years. For details, see text.
CLP/Ectodermal Dysplasia/Acral Anomalies
159
I
II
Ill
1
IV
V
Fig. 2. Pedigree of the family. 6 cleft lip; B cleft palate; 0 affected with the syndrome.
toe 5 (Fig. 4) with marked hypoplasia of the toenail, and lumbar lordosis. Dermatoglyphics showed hypoplastic lines, and the digital patterns were W, L", Wd, Wd, and L" at right, and L", W, W, W, and L" at left. Ophthalmologic and hearing evaluation were normal. Sweat pore studies of the hypothenar region (direct counting, and in alginate and polyvinyl glue impression) showed decreased number of palmar creases, sparce and small pores (mean of 6 pores/cm2).Results of routine laboratory blood tests were normal. Orthopantomographies performed at 13 and 23 years (Fig. 5) showed delayed dental development, with persistence of deciduous teeth, mesiodens, oligodontia, and microdontia. The missing permanent teeth according to the Palmer dental classification were
5 212 8 7 5 I
8
5 5
78 8
Roentgenograms of the appendicular skeleton showed bilateral camptodactyly of toe 4, and mild hypoplasia of toe 5, signs already seen by clinical examination. SEM analysis of hair shafts revealed different structural changes (Fig. 6 ) . DISCUSSION The ectodermal dysplasia subgroup 1-2-4 of FreireMaia's classification [1971, 19771now consists of 8 con-
Fig. 3. The hands of the proposita. For details, see text.
OFC 53 cm (25th-50th centile), inner canthal distance 3.5 cm (75th-97th centile), outer canthal distance 9.5 cm (75th-97th centile), and interpupillary distance 6.0 cm (75th-97th centile). She had high forehead, arched and dysplastic eyebrows (highly hypotrichotic at their lateral halves), hypoplastic lacrimal puncta, broad nose (including nose bridge), hypoplastic nasal alae, bilateral scars resulting from bilateral cleft lip/palate correction, sparse, coarse and straight hair, dry skin, hypohidrosis without hyperthermia (by history), marked proximal interdigital webbing between fingers 2-3-4 (Fig. 3), bilateral camptodactyly of toe 4 and hypoplastic
Fig. 4. The feet of the proposita. For details, see text.
160
Richiei-Costa et al. [Zlotogora et al., 1987; Ogur and Yuksel, 1988; Zlotogora and Ogur, 1988; Fbdini and Richieri-Costa, 1990b1, and the other of the subgroup 1-2, the Martinez syndrome [Martinez et al., 19871, share some signs with the patient here described, namely, trichodysplasia, dental defects, dyshidrosis, and dysplastic skin anomalies, among other signs (Table I). The main differential signs present in the Zlotogora-Ogur syndrome include mental retardation, as well as nipple and ear anomalies which are absent in our patient. Our patient resembles the Martinez syndrome, however, differing with respect to many signs (Table I). Another equally important difference is the pattern of inheritance, presumably autosomal dominant in the Martinez syndrome, and probably autosomal recessive in the present family. Taking into account these differences, we would like to suggest that the present condition is an apparently hitherto undescribed “new” syndrome. A final comment seems to be necessary. Note that in the inbred sibship under investigation, 3 apparently affected sibs (IV-3, IV-4, and IV-6) only had bilateral cleft liplpalate as the proposita (IV-9) who also had a number of other signs. Since there are, in the same family, 2 other cases of lip/palate clefts (111-1and 111-21, it is possible to develop the following hypotheses:
Fig. 5. Orthopantomograms performed at ages 13years (above) and 23 (below). For details, see text.
ditions: the F6ra syndrome (regional ectodermal dysplasia with total bilateral cleft), Berlin syndrome (leucomelanoderma), Book dysplasia, congenital insensitivity to pain with anhidrosis of Swanson, Lenz-Passarge dysplasia, Wesser-Vistnes ectodermal dysplasia with palatal paralysis, Johnson neuroectodermal syndrome [Johnson et al., 19831, and hypohidrotic ectodermal dysplasia with focal sweating [Gorlin, 19881 [for the first 6 conditions, see Freire-Maia and Pinheiro, 19841. Cleft lip/palate and isolated cleft palate have been reported in the Fara syndrome and in the Johnson neuroectodermal syndrome, respectively, but the whole clinical picture of these conditions clearly distinguish them from the present one. Ectodermal dysplasia sensu lato, cleft lip/palate, and limb anomalies are part of some well known syndromes [Rapp and Hodgkin, 1968; Rosselli and Gulienetti, 1961; Freire-Maia, 1970; Bowen and Armstrong, 1976; Hay and Wells, 1976; Allanson and McGillivray, 1985; Rodini et al., 1990; Rodini and Richieri-Costa 1990aI. The phenotype of the patient here described prompts a clear distinction with all the above mentioned conditions. Two of the conditions with CL/P and ED, one of the subgroup 1-2-3-4, the Zlotogora-Ogur syndrome
1. There are 6 persons (111-1, 111-2, IV-3, IV-4, IV-6, and IV-9) affected with cleft lip/palate. The proposita (IV-9), besides the lip/palate malformation, also presents by coincidence (“concurrence”)a syndrome characterized by the other signs presented in Table I. This hypothesis seems to be rather improbable since a high recurrence risk is not generally expected in lip/palate clefts. 2. At least one or %and possibly all 3 sibs-would have had the syndrome if they had survived early infancy. With this hypothesis, the segregation rate would be 418. By eliminating the proposita, the corrected segregation rate would turn out to be 3/7, which does not depart significantly from the expected 114 ratio (p= 1.19;P > 0.20, one degree of freedom). The same is true with respect to the most conservative hypothesis (only one sib with the condition):corrected segregation rate of 1/7; p = 0.43; P > 0.50.
ACKNOWLEDGMENTS The authors gratefully acknowledge the assistance of Miss Alba Regina Turin (Instituto de Tecnologia do Paranti) for the SEM photographs of the hair shafts of the proposita, and the CNPq for grants to the research projects of the group from the UFPR. M.P. and N.F.-M. are research fellows of CNPq. REFERENCES Allanson JE, McGillivray BC (1985):Familial clefting syndrome with ectropion and dental anomaly without limb anomalies. Clin Genet 27:426-429. Bowen P, Armstrong HB (1976): Ectodermal dysplasia, mental retardation, cleft lip/palate and other anomalies in three sibs. Clin Genet 935-42. Freire-Maia N (1970): A newly recognized genetic syndrome of tetramelic deficiencies, ectodermal dysplasia, deformed ears, and other abnormalities. Am J Hum Genet-22:370-377.
CLP/Ectodermal DysplasidAcral Anomalies
161
Fig. 6. SEM analysis of hair shafts of the proposita showing different longitudinal grooves.
Freire-MaiaN (1971): Ectodermal dysplasias. HumHered 21:309-312. Freire-Maia N (1977): Ectodermal dysplasias revisited. Acta Genet Med Gemellol 26:121-131. Freire-Maia N, Pinheiro M (1984): “Ectodermal Dysplasias: A Clinical and Genetic Study.” New York Alan R Liss. Gorlin RJ (1988): Selected ectodermal dysplasias. In Salinas CF, Opitz JM, Paul NW (eds): “Recent Advances in Ectodermal Dysplasias.” New York: Alan R. Liss, for the National Foundation-March of Dimes. BD:OAS XXIV (2):123-148. Hay RJ,Wells RS (1976): The syndrome of ankyloblepharon, ectoderma1 defects and cleft lip/palate: An autosomal dominant condition. Br J Dermatol 94:277-289. Johnson VP, McMillin JM, Aceto T, Jr, Bruins G (1983): A newly recognized neuroectodermal syndrome of familial alopecia, anosmia, deafness, and hypogonadism. Am J Med Genet 15:497-506. Martinez RB, Monasterio LA, Pinheiro M, Freire-Maia N (1987): Cleft lip/palate-oligodontia-syndactyly-hairalterations, a new syndrome: Review of the conditions combining ectodermal dysplasia and cleft liplpalate. Am J Med Genet 27:23-31. Michels VV, Hiltner HN, Beaudet AL (1978): A clefting syndrome with ocular anterior chamber defect and lid anomalies. J Pediatr 93:443-446.
Ogur G, Yuksel M (1988): Association of syndactyly, ectodermal dysplasia, and cleft lip and palate: report of two sibs from Turkey. J Med Genet 25:37-40. Rapp RS, Hodgkin WE (1968): Anhidrotic ectodermal dysplasia: Autosoma1 dominant inheritance with palate and lip anomalies. J Med Genet 5:269-272. Rodini ESO, likeitas JAS, Richieri-Costa A (1990).Rapp-Hodgkin syndrome: Report of a Brazilian family. Am J Med Genet 36:463-466. Rodini ESO, Richieri-Costa A (1990a): EEC syndrome: Report on 20 new patients, clinical and genetic considerations. Am J Med Genet 37:42-53. M i n i ESO, Rchieri-Costa A (1990b):Autosomal recessive ectodermal dysplasia, cleft lipipalate, mental retardation, and syndactyly: The Zlotogora-Ogur syndrome. Am J Med Genet 36:473-476. Rosselli D, Gulienetti R (1961):Edodermal dysplasia. Br J Plast Surg 14:190-204. Zlotogora J , Ogur G (1988): Syndactyly, ectodermal dysplasia, and cleft lip and palate. J Med Genet 25503. Zlotogora J, Zilberman Y, Tenenbaum A, Wexler MR (1987): Cleft lip and palate, pili torti, malformed ears, partial syndactyly of fingers and toes, and mental retardation: A new syndrome? J Med Genet 24:291-293.
162
Richiei-Costa et al.
TABLE I. Comparison Among Previously Described Similar Patients and the Present One Zlotogora-Ogur Syndromea Martinez syndrome Ogur and Rodini and Zlotogora et al. Yuksel Richieri-Costa Martinez et al. [19871 [19881 [1990b] [19871 1 1 1 1 Number of families + + Consanguineous parents + 2 2 5 1 Number of cases F M M 2 M b M M M F M SeX 8y 5,14,16y 4Y 4Y t8m 1Oy Age Craniofacial signs B L B B B B B L B Cleft lip + + + + + + + + + Cleft palate N R - - + Midface hypoplasia Brachycephaly N R + - + Prominent forehead + ? + + N R + + + + Micrognathia + + N R - - + + + N R + + + + Abnormal dentition + NR N R - - + Ocular hypertelorism Prominent eyes N R - - + Nose anomalies + + N R + + + + Abnormal ears + + + + N R + + + + Hair changes + + + + N R + + + Sparse scalp hair ? ? N R ? ? ? +Structural changes + + + + N R + + + Hypotrichotic eyebrows +NR N R - - + Two hair whorls Skin N R - - + + SimiadSydney line + + N R + + + Thick and/or dry skin + + ? + + N R + + + Abnormal nipples/areolae + + N R + + + Hypohidrosis Neuropsychological + NR + + N R + + + Mental retardation NR + + N R + + + Psychomotor retardation Limbs + + ++- Nm R -+ + + +Syndactyly Camptodactyly N R - - Hypoplastic 5th toes Other findings + + N R - - GU anomalies + NR N R - - NR Hypoplastic lacrimal puncta + N R - - Vertebral anomalies Inheritance AR AR AR AD?,AR?,XD?' "See also Zlotogora and Ogur [19881. bNeonatal death; M, male; F, female; B, bilateral; L, left; NR, not recorded since the children died very young. 'The mother of the proposita has a few mild clinical signs.
Present case 1
+
4? 1Mb,F,2Fb 23Y B
+
NR NR NR NR NR NR NR NR NR
B
B
-
NR NR NR
+ + + NR NR + NR NR + NR -
+
- N R
NR NR NR NR
+ +
NR NR NR NR
-
NR NR NR NR
-
NR NR
NR NR
+
-
+ + -
NR NR NR NR
NR NR NR
+ N R + N R
+
NR
NR NR NR
+ + +
NR NR NR
AR
