American Journal of Medical Genetics 36:273-274 (1990)
New Syndrome? ~
Blepharophimosis, Iris Coloboma, Microgenia, Hearing Loss, Postaxial Polydactyly, Aplasia of Corpus Callosum, Hydroureter, and Developmental Delay Inge Buntinx and F’rank Majewski Department of Medical Genetics, Wilrijk, Belgium (I.B.); Institute of Human Genetics, Diisseldorf, Federal Republic of Germany (F.M.)
KEY WORDS: postaxial polydactyly, blepharophimosis, iris coloboma, hearing loss, microgenia, developmental delay, agenesis of corpus callosum, reflux THE SYNDROME We describe a n apparently new combination of multiple congenital anomalies including postaxial polydactyly, bilateral blepharophimosis, unilateral iris coloboma, short nose, apparently low-set malformed ears with narrow external meati, bilateral hearing loss, microgenia, bilateral hydroureter, and absence of corpus callosum in a child with developmental delay.
logical examination: truncal hypotonia with increased tonus of the limbs. No abnormalities of hair, nails, skin, genitals. Chromosomes: normal (46,XY). Ophthalmologic examination: iris coloboma left, alternating strabism. Audiologic examination: bilateral conductive hearing loss 50 dB, bilateral sensorineural hearing loss 20-25 dB. IVP: bilateral reflux grade 111-IV. CT-scan and NMR of the brain: aplasia of corpus callosum (Fig. 3).
DISCUSSION The combination of the anomalies in our patient could not be classified among the known syndromes although there are various conditions with postaxial polydactyly (more than 20 syndromes) or blepharophimosis or iris coloboma and ear abnormalities a s a manifestation. CLINICAL REPORT Search of the London Database and of POSSUM was The propositus was the second child of a 25-year-old performed by using the following keywords in several combinations: postaxial polydactyly, blepharophimosis, G2P2 mother and her unrelated 46-year-old husband. An older boy was normal. Normal pregnancy. No history of agenesis of corpus callosum, iris coloboma, microgenia, alcohol or drug intake, radiation exposure, febral ill- and ear abnormalities. No match was found. POSSUM ness. Normal delivery a t 39 weeks. Birth weight 3.440 g, mostly favored the Miller-Dieker syndrome. This synlength 50 cm, OFC 34 cm. Neonatal period complicated drome is excluded by normal gyral pattern on CT-scan by poor suck and hypotonia, clenched hands. At age of 6 and normal chromosomes. The main differential diagmonths failure to thrive, weight 5.520 g (3rd centile), nostic possibilities were the association of iris coloboma, length 65 cm (10th centile), OFC 41 cm (3rd centile), ptosis, hypertelorism, and mental retardation [Barsevere developmental delay, bilateral conductive hear- aitser and Winter, 19881, the association of corpus caling loss (50 db), and unusual facial appearance (Figs. 1, losum agenesis, facial anomalies, and Robin sequence 2): prominent forehead, large anterior fontanel, [Toriello and Carey, 19883,and the association of mental blepharophimosis-epicanthus,upslanted palpebral fis- retardation, blepharophimosis, and hypoplastic teeth sures, iris coloboma left, short nose, anteverted nostrils, [Ohdo et al., 1986; Say and Barber, 19871. The condition described by Toriello and Carey [19881 apparently low-set, posteriorly angulated, round ears with very narrow external meati, microgenia, highly is very similar to that of our patient, but could not be arched palate, thick upper lip frenulum, postaxial poly- substantiated because of the different kind of abnormaldactyly of both hands (treated by surgery), unremark- ities of the hands (brachydactyly, no polydactyly) and able palmar creases, bilateral prominent heels. Neuro- the absence of iris coloboma. Another condition (which is also similar to the condition reported by Toriello and Received for publication February 22, 1989; revision received Carey [1988] was described by Ohdo et al. [1986] and Say and Barber [1987]. Their patients all had hypoplasOctober 23, 1989. Address reprint requests to Prof. F. Majewski, Institute of Hu- tic teeth. The 9 erupted teeth in our patient a t age 14 man Genetics, Moorenstr. 5 , 4000 Diisseldorf, F.R.G. months are normal; we think that some further signs in 0 1990 Wiley-Liss, Inc.
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Buntinx and Majewski
Fig. 3. NMR scan showing agenesis of the corpus callosum and normal gyral pattern.
Fig. 1. S.H. at age 3 weeks: prominent forehead, blepharophimosis, epicanthus, upslanted palpebral fissures, anteverted nostrils; clenched hands.
our patient (prominent forehead, iris coloboma, postaxial polydactyly) exclude this condition. Recently Opitz et al. [19891 described a “new” syn-
drome in a sporadic case. Main manifestations were bilateral microtia, hearing loss, hypoplastic mandible, small palpebral fissures, small nose, tetramelic postaxial hexadactyly, hypotonia, delayed motor development, hypermobile joints, and pigmentary dysplasia on chest and abdomen. This child probably has the same syndrome as our patient. Identical manifestations in both cases are: prominent forehead, large anterior fontanel, blepharophimosis, short or small nose, hypoplastic mandible, postaxial polydactyly, hypotonia, hearing loss, and developmental delay. Different symptoms were iris coloboma, agenesis of corpus callosum and bilateral reflux in our patient (the patient of Opitz et al. suffered from urinary tract infections), and hypermobile joints with genu recurvatum, pigmentary dysplasia, and microtia in Opitz et al.’s patient (but in our patient the external auditory meati were narrow). Both sporadic cases have similar manifestations of a new polydactyly syndrome, the etiology of which remains unclear. Since most of the more than 20 syndromes with postaxial polydactyly are autosomal recessive traits, this might be the most probable etiology of this new syndrome.
REFERENCES
Fig. 2. Short nose, apparently low-set posteriorly angulated round ears, hypoplastic mandible.
Baraitser M, Winter RM (1988): Iris coloboma, ptosis, hypertelorism, and mental retardation: A new syndrome? J Med Genet 25:41-43. Ohdo S, Madokoro H, Sonoda T, Hayakawa K (1986):Mental retardation associated with congenital heart disease, blepharophimosis and hypoplastic teeth. J Med Genet 23:242-244. Opitz JM, Reynolds J F , Fitzgerald J (1989):Mandibulofacialdysostosis or bilateral hemifacial microsomia with hearing loss, telecanthus, tetramelic postaxial hexadactyly, congenital hypotonia and lymphedema withjoint hypermobility and pigmentary dysplasia: A new syndrome? Am J Med Genet 33:433-435. Say B, Barber N (1987):Mental retardation with blepharophimosis. J Med Genet 24511. Toriello HU, Carey J C (1988):Corpus callosum agenesis, facial anomalies, Robin sequence, and other anomalies: A new autosomal recessive syndrome? Am J Med Genet 31:17-23.
New Syndrome? ~
Blepharophimosis, Iris Coloboma, Microgenia, Hearing Loss, Postaxial Polydactyly, Aplasia of Corpus Callosum, Hydroureter, and Developmental Delay Inge Buntinx and F’rank Majewski Department of Medical Genetics, Wilrijk, Belgium (I.B.); Institute of Human Genetics, Diisseldorf, Federal Republic of Germany (F.M.)
KEY WORDS: postaxial polydactyly, blepharophimosis, iris coloboma, hearing loss, microgenia, developmental delay, agenesis of corpus callosum, reflux THE SYNDROME We describe a n apparently new combination of multiple congenital anomalies including postaxial polydactyly, bilateral blepharophimosis, unilateral iris coloboma, short nose, apparently low-set malformed ears with narrow external meati, bilateral hearing loss, microgenia, bilateral hydroureter, and absence of corpus callosum in a child with developmental delay.
logical examination: truncal hypotonia with increased tonus of the limbs. No abnormalities of hair, nails, skin, genitals. Chromosomes: normal (46,XY). Ophthalmologic examination: iris coloboma left, alternating strabism. Audiologic examination: bilateral conductive hearing loss 50 dB, bilateral sensorineural hearing loss 20-25 dB. IVP: bilateral reflux grade 111-IV. CT-scan and NMR of the brain: aplasia of corpus callosum (Fig. 3).
DISCUSSION The combination of the anomalies in our patient could not be classified among the known syndromes although there are various conditions with postaxial polydactyly (more than 20 syndromes) or blepharophimosis or iris coloboma and ear abnormalities a s a manifestation. CLINICAL REPORT Search of the London Database and of POSSUM was The propositus was the second child of a 25-year-old performed by using the following keywords in several combinations: postaxial polydactyly, blepharophimosis, G2P2 mother and her unrelated 46-year-old husband. An older boy was normal. Normal pregnancy. No history of agenesis of corpus callosum, iris coloboma, microgenia, alcohol or drug intake, radiation exposure, febral ill- and ear abnormalities. No match was found. POSSUM ness. Normal delivery a t 39 weeks. Birth weight 3.440 g, mostly favored the Miller-Dieker syndrome. This synlength 50 cm, OFC 34 cm. Neonatal period complicated drome is excluded by normal gyral pattern on CT-scan by poor suck and hypotonia, clenched hands. At age of 6 and normal chromosomes. The main differential diagmonths failure to thrive, weight 5.520 g (3rd centile), nostic possibilities were the association of iris coloboma, length 65 cm (10th centile), OFC 41 cm (3rd centile), ptosis, hypertelorism, and mental retardation [Barsevere developmental delay, bilateral conductive hear- aitser and Winter, 19881, the association of corpus caling loss (50 db), and unusual facial appearance (Figs. 1, losum agenesis, facial anomalies, and Robin sequence 2): prominent forehead, large anterior fontanel, [Toriello and Carey, 19883,and the association of mental blepharophimosis-epicanthus,upslanted palpebral fis- retardation, blepharophimosis, and hypoplastic teeth sures, iris coloboma left, short nose, anteverted nostrils, [Ohdo et al., 1986; Say and Barber, 19871. The condition described by Toriello and Carey [19881 apparently low-set, posteriorly angulated, round ears with very narrow external meati, microgenia, highly is very similar to that of our patient, but could not be arched palate, thick upper lip frenulum, postaxial poly- substantiated because of the different kind of abnormaldactyly of both hands (treated by surgery), unremark- ities of the hands (brachydactyly, no polydactyly) and able palmar creases, bilateral prominent heels. Neuro- the absence of iris coloboma. Another condition (which is also similar to the condition reported by Toriello and Received for publication February 22, 1989; revision received Carey [1988] was described by Ohdo et al. [1986] and Say and Barber [1987]. Their patients all had hypoplasOctober 23, 1989. Address reprint requests to Prof. F. Majewski, Institute of Hu- tic teeth. The 9 erupted teeth in our patient a t age 14 man Genetics, Moorenstr. 5 , 4000 Diisseldorf, F.R.G. months are normal; we think that some further signs in 0 1990 Wiley-Liss, Inc.
274
Buntinx and Majewski
Fig. 3. NMR scan showing agenesis of the corpus callosum and normal gyral pattern.
Fig. 1. S.H. at age 3 weeks: prominent forehead, blepharophimosis, epicanthus, upslanted palpebral fissures, anteverted nostrils; clenched hands.
our patient (prominent forehead, iris coloboma, postaxial polydactyly) exclude this condition. Recently Opitz et al. [19891 described a “new” syn-
drome in a sporadic case. Main manifestations were bilateral microtia, hearing loss, hypoplastic mandible, small palpebral fissures, small nose, tetramelic postaxial hexadactyly, hypotonia, delayed motor development, hypermobile joints, and pigmentary dysplasia on chest and abdomen. This child probably has the same syndrome as our patient. Identical manifestations in both cases are: prominent forehead, large anterior fontanel, blepharophimosis, short or small nose, hypoplastic mandible, postaxial polydactyly, hypotonia, hearing loss, and developmental delay. Different symptoms were iris coloboma, agenesis of corpus callosum and bilateral reflux in our patient (the patient of Opitz et al. suffered from urinary tract infections), and hypermobile joints with genu recurvatum, pigmentary dysplasia, and microtia in Opitz et al.’s patient (but in our patient the external auditory meati were narrow). Both sporadic cases have similar manifestations of a new polydactyly syndrome, the etiology of which remains unclear. Since most of the more than 20 syndromes with postaxial polydactyly are autosomal recessive traits, this might be the most probable etiology of this new syndrome.
REFERENCES
Fig. 2. Short nose, apparently low-set posteriorly angulated round ears, hypoplastic mandible.
Baraitser M, Winter RM (1988): Iris coloboma, ptosis, hypertelorism, and mental retardation: A new syndrome? J Med Genet 25:41-43. Ohdo S, Madokoro H, Sonoda T, Hayakawa K (1986):Mental retardation associated with congenital heart disease, blepharophimosis and hypoplastic teeth. J Med Genet 23:242-244. Opitz JM, Reynolds J F , Fitzgerald J (1989):Mandibulofacialdysostosis or bilateral hemifacial microsomia with hearing loss, telecanthus, tetramelic postaxial hexadactyly, congenital hypotonia and lymphedema withjoint hypermobility and pigmentary dysplasia: A new syndrome? Am J Med Genet 33:433-435. Say B, Barber N (1987):Mental retardation with blepharophimosis. J Med Genet 24511. Toriello HU, Carey J C (1988):Corpus callosum agenesis, facial anomalies, Robin sequence, and other anomalies: A new autosomal recessive syndrome? Am J Med Genet 31:17-23.
