American Journal of Medical Genetics 42340-342 (1992)
New Syndrome? Autosomal Recessive Blepharoptosis, Cleft Lip/Palate, Dental Anomalies, and Ectrodactyly E.S.O. Rodini and A. Richieri-Costa Servko de Genktica Clinica, Hospital de Pesquisa e Reabilitqh ci?eLes6es Labw-Palntais, Universidade de Sbo Paulo, Bauru, SP, Brazil
KEY WORDS: blepharoptosis, cleft lip/palate, dental anomalies,ectrodactyly, consanguinity, autosomal recessive inheritance
I
It
1-2
THE SYNDROME We report on a Brazilian girl (F = 1/32),born to consanguineous parents with an apparently new combination of multiple congenital anomalies including blepharoptosis, cleft lip/palate, abnormal teeth, and ectrodactyly of feet.
111
1-12
N
CLINICAL REPORT The proposita (Fig. 1, IV-1) was born at term after an uncomplicated first pregnancy to a 29-year-old mother and her related P/2 second cousin) 33-year-old husband. Vertex delivery was spontaneous and the birth weight was 2,250 g (< 3rd centile), length was 47 cm (< 10th centile), and OFC was not recorded. Cleft lip/ palate and foot anomalies were noted a t birth. Neuropsychological development was normal. The proposita’s father and a parental aunt presented cleft lip/palate, and the other relatives were considered as normal (Fig. 1). Clinical examination a t age 6 years showed a height of 105 cm (< 10th centile), weight 17,500 g (10th centile), OFC 51.8 cm (50th centile), ICD 2.9 cm (> 50th centile), and OCD 9.8 cm (> 97 centile). She had bilateral ptosis of the eyelids, surgical scars resulting from cleft lip/ palate correction (Fig. 21, malpositioned and coneshaped teeth (Fig. 31, ectrodactyly of left foot, and syndactylous toes 4-5, hypoplastic toe 3, and absent toenails 2-3 at right (Fig. 4). Radiological examination showed hypoplastic middle/ distal phalanges of toes 2-5 and cutaneous syndactyly between toes 4 and 5 at right, distal osseous syndactyly between proximal phalanges of toes 2-3, complete osReceived for publication March 6,1991; revision received June 18, 1991. Address reprint requests to A. Richieri-Costa,Servico de Genktica Clinica, Hospital de Pesquisa e Reabilitacb de Lesijes LAbio-Palatais, USP, P.O. Box 620, 17043 Bauru, SP, Brazil.
0 1992 Wiley-Liss, Inc.
I
2
Fig. 1. Family pedigree. (8,0 )cleft lip/palate; (0)cleft lip/palate, dental anomalies, ectrodactyly.
Fig. 2. Frontal aspect of the face of the proposita.
New Syndrome
341
Fig. 3. Clinical aspects of the teeth of the proposita.
Fig. 5. Radiological aspects of the feet of the proposita.
seous syndactyly between middle phalanges of toes 2-3, and absent distal phalanges of toes 2-3 a t left (Fig. 5).
DISCUSSION Clefting associated with limb and dental anomalies is present in autosomal dominant [Rapp and Hodgkin, 1962; Rudiger et al., 1970; Hay and Wells, 1976; Bowen and Armstrong, 1976; Lewis and Pashayan, 1981; Allanson and McGillivray, 1985; Thompson et al., 1985; Martinez et al., 1987;Rodini and Richieri-Costa, 1990al and autosomal recessive syndromes [Rosselli and Gulienetti, 1968; F’reire-Maia, 1970; Zlotogora et al., 1987; Ogur and Yuksel, 1988; Rodini and RichieriCosta, 1990bl.The cluster of anomalies presented by our patient seems to be different from all the conditions listed above (Table I). Parental consanguinity suggests autosomal recessive inheritance, however, the presence of cleft lipipalate in the father and in an aunt of the
Fig. 4. Clinical aspects of the feet of the proposita.
TABLE I. Main Differential Conditions With the Present Case
Ectrodact yly Syndacty ly Cleft lip/palate Skin anomalies Hair changes Dental anomalies Onicodysplasia Hypohidrosis Tear duct anomalies Mental retardation Hearing anomalies Genitourinary anomalies Abnormal ears Ptosis Inheritance
EEC
AEC
Ladd
RappT Hodgkin
RosselliGulienetti
BowenArmstrong
ZlotogoraOgur
Martinez syndrome
Present case
+
-
-
-
+
-
-
+ +-
-
-
+ + + + + + + +
+ + + + + ++
+ + + + +-
+ ++ + +
+
+ + + + + + + + i
+ -
i
-
-
-
+-
AD
AD
k
-
-
+-
+ + -
+
+ + + +-
++ + + -
-
-
++
+ -
+
+ + -
-
-
+ + + -
AD
AD
AR
AR
AR
-
-
+
+
-
-
-
AD?XL?
+ +-
+ -
AR?
342
Rodini and Richieri-Costa
dysproposita could suggest an incomplete form of a Ogur G, Yuksel M (1988): Association of syndactyly, ectodermal plasia, and cleft lip and palate: Report of two sibs from Turkey. J pleiotropic dominant (autosomal or X-linked) condition. Med Genet 25:37-40. Reports of patients with similar conditions are highly Rapp RS,Hodgkin WE (1968):Anhidrotic ectodermal dysplasia: Autodesirable concerning the elucidation of the etiological soma1 dominant inheritance with palate and lip anomalies. J Med Genet 5:269-272. mechanisms.
REFERENCES Allanson JE, McGillivray BC (1986):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, clef lipipalate and other anomalies in three sibs. Clin Genet 9:35-42. Freire-Maia N (1970): A newly recognized genetic syndrome of tretamelic deficiencies, ectodermal dysplasia, deformed ears, and other abnormalities. Am J Hum Genet 22:370-377. Hay RJ,Wells RS (1976):The syndrome of ankyloblepharon, ectoderma1 defects and cleft lip and palate: an autosomal dominant condition. Br J Dermatol 94:277-289. Lewis MB, Pashayan, HM (1981):Ectrodactyly, cleft lip and palate in two half sibs. J Med Genet 18:394-396. 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 lipipalate. Am J Med Genet 27:23-31.
M i n i ESO, Richieri-Costa A (1990a):Brief clinical report: Autosomal recessive ectodermal dysplasia, cleft lip/palate, mental retardation, and syndactyly: The Zlotogora-Ogur syndrome. Am J Med Genet 36:473-466. M i n i ESO, Richieri-Costa A (1990b): EEC syndrome-Report on 20 new patients, clinical and genetic considerations. Am J Med Genet 37:42-53. Rosselli D, Gulienetti R (1961):Ectodermal dysplasia. Br J Plast Surg 14~190-204. Rudiger RA, Haase W, Passarge E (1970): Association of ectrodactyly, ectodermal dysplasia, and cleft lip-palate. The EEC syndrome. Am J Dis Child 120:160-163. Thompson E, Pembrey M, Graham J (1985): Phenotypic variation in LADD syndrome. J Med Genet 22:382-385. Zlotogora J , Zilberman Y, Tenebaum 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.
New Syndrome? Autosomal Recessive Blepharoptosis, Cleft Lip/Palate, Dental Anomalies, and Ectrodactyly E.S.O. Rodini and A. Richieri-Costa Servko de Genktica Clinica, Hospital de Pesquisa e Reabilitqh ci?eLes6es Labw-Palntais, Universidade de Sbo Paulo, Bauru, SP, Brazil
KEY WORDS: blepharoptosis, cleft lip/palate, dental anomalies,ectrodactyly, consanguinity, autosomal recessive inheritance
I
It
1-2
THE SYNDROME We report on a Brazilian girl (F = 1/32),born to consanguineous parents with an apparently new combination of multiple congenital anomalies including blepharoptosis, cleft lip/palate, abnormal teeth, and ectrodactyly of feet.
111
1-12
N
CLINICAL REPORT The proposita (Fig. 1, IV-1) was born at term after an uncomplicated first pregnancy to a 29-year-old mother and her related P/2 second cousin) 33-year-old husband. Vertex delivery was spontaneous and the birth weight was 2,250 g (< 3rd centile), length was 47 cm (< 10th centile), and OFC was not recorded. Cleft lip/ palate and foot anomalies were noted a t birth. Neuropsychological development was normal. The proposita’s father and a parental aunt presented cleft lip/palate, and the other relatives were considered as normal (Fig. 1). Clinical examination a t age 6 years showed a height of 105 cm (< 10th centile), weight 17,500 g (10th centile), OFC 51.8 cm (50th centile), ICD 2.9 cm (> 50th centile), and OCD 9.8 cm (> 97 centile). She had bilateral ptosis of the eyelids, surgical scars resulting from cleft lip/ palate correction (Fig. 21, malpositioned and coneshaped teeth (Fig. 31, ectrodactyly of left foot, and syndactylous toes 4-5, hypoplastic toe 3, and absent toenails 2-3 at right (Fig. 4). Radiological examination showed hypoplastic middle/ distal phalanges of toes 2-5 and cutaneous syndactyly between toes 4 and 5 at right, distal osseous syndactyly between proximal phalanges of toes 2-3, complete osReceived for publication March 6,1991; revision received June 18, 1991. Address reprint requests to A. Richieri-Costa,Servico de Genktica Clinica, Hospital de Pesquisa e Reabilitacb de Lesijes LAbio-Palatais, USP, P.O. Box 620, 17043 Bauru, SP, Brazil.
0 1992 Wiley-Liss, Inc.
I
2
Fig. 1. Family pedigree. (8,0 )cleft lip/palate; (0)cleft lip/palate, dental anomalies, ectrodactyly.
Fig. 2. Frontal aspect of the face of the proposita.
New Syndrome
341
Fig. 3. Clinical aspects of the teeth of the proposita.
Fig. 5. Radiological aspects of the feet of the proposita.
seous syndactyly between middle phalanges of toes 2-3, and absent distal phalanges of toes 2-3 a t left (Fig. 5).
DISCUSSION Clefting associated with limb and dental anomalies is present in autosomal dominant [Rapp and Hodgkin, 1962; Rudiger et al., 1970; Hay and Wells, 1976; Bowen and Armstrong, 1976; Lewis and Pashayan, 1981; Allanson and McGillivray, 1985; Thompson et al., 1985; Martinez et al., 1987;Rodini and Richieri-Costa, 1990al and autosomal recessive syndromes [Rosselli and Gulienetti, 1968; F’reire-Maia, 1970; Zlotogora et al., 1987; Ogur and Yuksel, 1988; Rodini and RichieriCosta, 1990bl.The cluster of anomalies presented by our patient seems to be different from all the conditions listed above (Table I). Parental consanguinity suggests autosomal recessive inheritance, however, the presence of cleft lipipalate in the father and in an aunt of the
Fig. 4. Clinical aspects of the feet of the proposita.
TABLE I. Main Differential Conditions With the Present Case
Ectrodact yly Syndacty ly Cleft lip/palate Skin anomalies Hair changes Dental anomalies Onicodysplasia Hypohidrosis Tear duct anomalies Mental retardation Hearing anomalies Genitourinary anomalies Abnormal ears Ptosis Inheritance
EEC
AEC
Ladd
RappT Hodgkin
RosselliGulienetti
BowenArmstrong
ZlotogoraOgur
Martinez syndrome
Present case
+
-
-
-
+
-
-
+ +-
-
-
+ + + + + + + +
+ + + + + ++
+ + + + +-
+ ++ + +
+
+ + + + + + + + i
+ -
i
-
-
-
+-
AD
AD
k
-
-
+-
+ + -
+
+ + + +-
++ + + -
-
-
++
+ -
+
+ + -
-
-
+ + + -
AD
AD
AR
AR
AR
-
-
+
+
-
-
-
AD?XL?
+ +-
+ -
AR?
342
Rodini and Richieri-Costa
dysproposita could suggest an incomplete form of a Ogur G, Yuksel M (1988): Association of syndactyly, ectodermal plasia, and cleft lip and palate: Report of two sibs from Turkey. J pleiotropic dominant (autosomal or X-linked) condition. Med Genet 25:37-40. Reports of patients with similar conditions are highly Rapp RS,Hodgkin WE (1968):Anhidrotic ectodermal dysplasia: Autodesirable concerning the elucidation of the etiological soma1 dominant inheritance with palate and lip anomalies. J Med Genet 5:269-272. mechanisms.
REFERENCES Allanson JE, McGillivray BC (1986):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, clef lipipalate and other anomalies in three sibs. Clin Genet 9:35-42. Freire-Maia N (1970): A newly recognized genetic syndrome of tretamelic deficiencies, ectodermal dysplasia, deformed ears, and other abnormalities. Am J Hum Genet 22:370-377. Hay RJ,Wells RS (1976):The syndrome of ankyloblepharon, ectoderma1 defects and cleft lip and palate: an autosomal dominant condition. Br J Dermatol 94:277-289. Lewis MB, Pashayan, HM (1981):Ectrodactyly, cleft lip and palate in two half sibs. J Med Genet 18:394-396. 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 lipipalate. Am J Med Genet 27:23-31.
M i n i ESO, Richieri-Costa A (1990a):Brief clinical report: Autosomal recessive ectodermal dysplasia, cleft lip/palate, mental retardation, and syndactyly: The Zlotogora-Ogur syndrome. Am J Med Genet 36:473-466. M i n i ESO, Richieri-Costa A (1990b): EEC syndrome-Report on 20 new patients, clinical and genetic considerations. Am J Med Genet 37:42-53. Rosselli D, Gulienetti R (1961):Ectodermal dysplasia. Br J Plast Surg 14~190-204. Rudiger RA, Haase W, Passarge E (1970): Association of ectrodactyly, ectodermal dysplasia, and cleft lip-palate. The EEC syndrome. Am J Dis Child 120:160-163. Thompson E, Pembrey M, Graham J (1985): Phenotypic variation in LADD syndrome. J Med Genet 22:382-385. Zlotogora J , Zilberman Y, Tenebaum 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.
