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Congenital ptosis and associated congenital malformations
Congenital Ptosis and Associated Congenital Malformations Nurgu¨l Yılmaz, MD, Banu M. Hos¸al, and Gu¨ler Zileliog˜lu We report a case of unilateral congenital ptosis which is associated with ocular and systemic congenital malformations including mild microphthalmia, microcornea, cataract, iris and chorioretinal coloboma, ectopic kidney, and ventricular septal defect. An inciting factor, acting during the second month of gestation, may affect the development of the eye, heart, and abdomen and may lead to congenital malformations. Although congenital ptosis rarely presents with ocular and systemic congenital malformations, ophthalmologists should be alert for the possibility of coexisting structural defects. Congenital ptosis is a muscular dystrophy demonstrated by various degrees of muscular degeneration and it may rarely be associated with ocular1,2 and systemic congenital malformation.3 Here, we report a case of congenital ptosis associated with more than one ocular and systemic malformation.
CASE REPORT An 8-year-old girl was admitted to the outpatient clinic for the lowering in her right upper eyelid. Her medical history revealed that she had ventricular septal defect and a left ectopic kidney. Neither of her parents, nor any of four siblings, had any eye or systemic abnormalities. There was no history of consanguinity, but there was a history of antibiotic use in the second month of pregnancy. Her mother used an unknown antibiotic for 2 weeks because of respiratory tract infection. Chromosomal analysis and neurologic examination of the patient were normal. On examination, best-corrected visual acuity was counting fingers at 1 meter in the right and 20/20 in the left eye. The cycloplegic refraction was ⫹4.25 (⫹3.25 ⫻ 180°) and ⫹1.0, respectively. Palpebral fissures were 7 mm in the right and 10 mm in the left eye. The levator function was 5 mm in the right eye and 15 mm in the left eye. There was a relative afferent pupillary defect and the ptosis was obstructing the visual axis. She had right upper eyelid retraction in downgaze. Hypertropia was present in the right eye (Figures 1A and 1B). There was no sign of a trochlear nerve palsy. Orbicularis muscle function and
From the Department of Ophthalmology, Ankara University Faculty of Medicine, Ankara, Turkey. Reprint requests: Nurgu¨l Yılmaz, MD, Burcu Sitesi, no: 16/31, 451. Sokak, C¸ukurambar, Ankara, Turkey; e-mail: [email protected] J AAPOS 2004;8:293-295. Copyright © 2004 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/2004/$35.00 ⫹ 0 doi:10.1016/j.jaapos.2004.03.002
Journal of AAPOS
FIG 1. (A) Demonstrates ptosis, hypertropia. (B) Lid retraction in downgaze in the right eye.
Bell’s phenomenon were good. Slit-lamp examination of the right eye demonstrated iris coloboma and anterior subcapsular lens opacity inferiorly (Figure 2). Fundus examination of the right eye revealed large inferior chorioretinal coloboma with normal optic nerve and macular region (Figure 3). The slit-lamp and funduscopic examinations of the left eye were normal. Corneal diameters were 9 mm in the right eye and 11 mm in the left eye horizontally. Axial lengths measured by A-scan ultrasonography were 22.32 mm in the right eye and 23.57 mm in the left eye. Spectacles were prescribed and occlusion therapy was initiated, but visual acuity did not improve. After she had an operation for ventricular septal defect, levator resection was performed. After surgery, the palpebral fissure increased only one millimeter. The biopsy of the levator muscle revealed diffuse fibrous and adipose tissue that contain islands of striated muscle cells.
DISCUSSION An association of congenital ptosis with ocular malformations like aniridia, iris coloboma, microcornea, microphJune 2004
293
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Yılmaz, Hos¸al, and Zileliog˜lu
FIG 2. Demonstrates microcornea and inferior iris coloboma.
FIG 3. Demonstrates inferior chorioretinal coloboma.
thalmia, cataract, optic nerve hypoplasia, colobomatous defect of the optic disc, nystagmus, and strabismus have been reported in previous studies.1,2 We reported herein a case of congenital ptosis associated with ocular (mild microphthalmia, microcornea, cataract, iris, and chorioretinal coloboma) and systemic (congenital heart disease and left ectopic kidney) congenital malformations. As far as we know, there is not a case in the literature including these structural malformations. These malformations are quite rare and the chance of association in a single case is unlikely. It is possible that an inciting factor, maybe an antibiotic use as in this case, may affect the development of different systems in the same embryonic period and lead to congenital malformations. When the fetal fissure fails to close during the sixth and seventh weeks of gestation, a cleft persists. Although such a cleft may only locate in the iris, it may also extend to the ciliary body, retina, choroids, and the optic nerve.4 Earlyonset cataracts (posterior subcapsular, anterior cortical) are frequently associated with abnormal closure of the fetal fissure and hyaloid vascular abnormalities. In the same quadrant of the eye in which the colobomas occur, the lens bow is disrupted and the lens epithelium differentiates abnormally.5 Salmon et al6 suggested that the size of cor-
Journal of AAPOS Volume 8 Number 3 June 2004
nea may be determined by neural crest cells, rather than the position of the anterior tips of the optic cup in the embryo. Migration of the neural crest origin cells from the margin of the optic cup evolves into the anterior segment of the human eye at sixth week of gestation and microcornea occurs as a result of faulty migration or function of the first wave of neural crest cells.6 Mild microphthalmia adds further evidence of global ocular arrest during embryogenesis. Formation of the interventricular septum of the heart occurs between the fifth and eighth week of gestation. The observed rate of congenital heart disease, in otherwise normal congenital ptosis patients, was five times more often than the expected rate in the pediatric population.3 The permanent kidney appears in the fifth week and ascent of the kidney from the pelvic region to more cranial position begins after the fifth week of gestation. If the kidneys fail to ascent, ectopic localization of the kidney occurs.4 Since all of these congenital malformations occur in the second month of gestation, an external insult, like antibiotics, may affect the development of embryonic structures. While unilateral maldevelopment secondary to an embryonic teratogen is not uncommon, one would more likely expect bilateral ocular abnormalities, especially if the exposure is early in gestation. We also do not know why the levator muscle was affected since its development occurs later than the closure of the fetal fissure and the development of the cornea. Recently, several genetic studies have been done to identify the possible cause of congenital ptosis. Especially, twin studies seem to support the idea of inheritance in these cases. Also, gene mutations like PAX6 mutation or those detected in syndromes such as Ohdo blepharophimosis syndrome and Oculo-facio-cardio-dental syndrome were proposed to be responsible for the presence of congenital ptosis. These rare mutations may help us while evaluating such cases.2,7-9 Although congenital ptosis rarely present with systemic and ocular congenital malformations, the possibility of coexisting structural defects must not be overlooked. References 1. Pallotta R. Iris coloboma, ptosis, hypertelorism, and mental retardation: a new syndrome possibly localized on chromosome 2. J Med Genet 1991;28:342-4. 2. Malandrini A, Mari F, Palmeri S, Gambelli S, Berti G, Brutini M, et al. PAX6 mutation in a family with aniridia, congenital ptosis, and mental retardation. Clin Genet 2001;2001:151-4. 3. Larned DC, Flanagan JC, Nelson LE, Harley RO, Wilson TW, et al. The association of congenital ptosis and congenital heart disease. Ophthalmology 1986;93:492-4. 4. Sadler TW. Langman’s medical embryology. Baltimore: Williams & Wilkins; 1990. pp. 196-8, 266-8, 345. 5. Burns RP, Anderson RS, Feeney-Burns L. Cataract-webbed trait in Peromyscus. II. Biomicroscopy and histology of eyes. Invest Ophthalmol Vis Sci 1980;19:31-41. 6. Salmon JF, Wallis CE, Murray ADN. Variable expressivity of auto-
Journal of AAPOS Volume 8 Number 3 June 2004
Yılmaz, Hos¸al, and Zileliog˜lu
somal dominant microcornea with cataract. Arch Ophthalmol 1988; 106:505-10. 7. Mhanni AA, Dawson AJ, Chudley AE. Vertical transmission of the Ohdo blepharophimosis syndrome. Am J Med Genet 1998;77:144-8. 8. Schulze BR, Horn D, Kobelt A, Tariverdian G, Stellzig A, et al. Rare
295
dental abnormalities seen in oculo-facio-cardio-dental (OFCD) syndrome: three new cases and review of nine patients. Am J Med Genet 1999;82:429-35. 9. Vestal KP, Seiff SR, Lahey JM. Congenital ptosis in monozygotic twins. Opthal Plast Reconstr Surg 1990;6:265-8.
An Eye on the Arts – The Arts on the Eye
I would conquer space by hurtling through it. I wore telescopic glasses, suffered from crushing headaches, but still chose to ride a bicycle—with nothing more than adrenaline for assurance. How do you ride a bicycle when you can’t see? You hold your head like a stiff flower and tilt toward the light. You think not at all about your chances—the sheer physicality of gutters and pavements. One submits to Holy Rule and spins ahead. Picture this: A darkness rises. Is it a tree or a shadow? A shadow or a truck? The thrill of the high wire is the greatest wonder of the brain. There is, at the center of our skulls, a terrible glittering, a requiem light. I lower my face to the cold handlebars and decide it’s a shadow, a hole in sunlight, and pedal straight through. Here’s another shadow, and another. I turn sharply but this time plunge into tall weeds. Insects rise into my hair, cling to my sweaty face. From the road comes the hiss of angered gravel, a car roars past. Thanks be to God! I’m alive in the wild carrot leaf! —Stephen Kuusisto (from Planet of the Blind)
CASE REPORT An 8-year-old girl was admitted to the outpatient clinic for the lowering in her right upper eyelid. Her medical history revealed that she had ventricular septal defect and a left ectopic kidney. Neither of her parents, nor any of four siblings, had any eye or systemic abnormalities. There was no history of consanguinity, but there was a history of antibiotic use in the second month of pregnancy. Her mother used an unknown antibiotic for 2 weeks because of respiratory tract infection. Chromosomal analysis and neurologic examination of the patient were normal. On examination, best-corrected visual acuity was counting fingers at 1 meter in the right and 20/20 in the left eye. The cycloplegic refraction was ⫹4.25 (⫹3.25 ⫻ 180°) and ⫹1.0, respectively. Palpebral fissures were 7 mm in the right and 10 mm in the left eye. The levator function was 5 mm in the right eye and 15 mm in the left eye. There was a relative afferent pupillary defect and the ptosis was obstructing the visual axis. She had right upper eyelid retraction in downgaze. Hypertropia was present in the right eye (Figures 1A and 1B). There was no sign of a trochlear nerve palsy. Orbicularis muscle function and
From the Department of Ophthalmology, Ankara University Faculty of Medicine, Ankara, Turkey. Reprint requests: Nurgu¨l Yılmaz, MD, Burcu Sitesi, no: 16/31, 451. Sokak, C¸ukurambar, Ankara, Turkey; e-mail: [email protected] J AAPOS 2004;8:293-295. Copyright © 2004 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/2004/$35.00 ⫹ 0 doi:10.1016/j.jaapos.2004.03.002
Journal of AAPOS
FIG 1. (A) Demonstrates ptosis, hypertropia. (B) Lid retraction in downgaze in the right eye.
Bell’s phenomenon were good. Slit-lamp examination of the right eye demonstrated iris coloboma and anterior subcapsular lens opacity inferiorly (Figure 2). Fundus examination of the right eye revealed large inferior chorioretinal coloboma with normal optic nerve and macular region (Figure 3). The slit-lamp and funduscopic examinations of the left eye were normal. Corneal diameters were 9 mm in the right eye and 11 mm in the left eye horizontally. Axial lengths measured by A-scan ultrasonography were 22.32 mm in the right eye and 23.57 mm in the left eye. Spectacles were prescribed and occlusion therapy was initiated, but visual acuity did not improve. After she had an operation for ventricular septal defect, levator resection was performed. After surgery, the palpebral fissure increased only one millimeter. The biopsy of the levator muscle revealed diffuse fibrous and adipose tissue that contain islands of striated muscle cells.
DISCUSSION An association of congenital ptosis with ocular malformations like aniridia, iris coloboma, microcornea, microphJune 2004
293
294
Yılmaz, Hos¸al, and Zileliog˜lu
FIG 2. Demonstrates microcornea and inferior iris coloboma.
FIG 3. Demonstrates inferior chorioretinal coloboma.
thalmia, cataract, optic nerve hypoplasia, colobomatous defect of the optic disc, nystagmus, and strabismus have been reported in previous studies.1,2 We reported herein a case of congenital ptosis associated with ocular (mild microphthalmia, microcornea, cataract, iris, and chorioretinal coloboma) and systemic (congenital heart disease and left ectopic kidney) congenital malformations. As far as we know, there is not a case in the literature including these structural malformations. These malformations are quite rare and the chance of association in a single case is unlikely. It is possible that an inciting factor, maybe an antibiotic use as in this case, may affect the development of different systems in the same embryonic period and lead to congenital malformations. When the fetal fissure fails to close during the sixth and seventh weeks of gestation, a cleft persists. Although such a cleft may only locate in the iris, it may also extend to the ciliary body, retina, choroids, and the optic nerve.4 Earlyonset cataracts (posterior subcapsular, anterior cortical) are frequently associated with abnormal closure of the fetal fissure and hyaloid vascular abnormalities. In the same quadrant of the eye in which the colobomas occur, the lens bow is disrupted and the lens epithelium differentiates abnormally.5 Salmon et al6 suggested that the size of cor-
Journal of AAPOS Volume 8 Number 3 June 2004
nea may be determined by neural crest cells, rather than the position of the anterior tips of the optic cup in the embryo. Migration of the neural crest origin cells from the margin of the optic cup evolves into the anterior segment of the human eye at sixth week of gestation and microcornea occurs as a result of faulty migration or function of the first wave of neural crest cells.6 Mild microphthalmia adds further evidence of global ocular arrest during embryogenesis. Formation of the interventricular septum of the heart occurs between the fifth and eighth week of gestation. The observed rate of congenital heart disease, in otherwise normal congenital ptosis patients, was five times more often than the expected rate in the pediatric population.3 The permanent kidney appears in the fifth week and ascent of the kidney from the pelvic region to more cranial position begins after the fifth week of gestation. If the kidneys fail to ascent, ectopic localization of the kidney occurs.4 Since all of these congenital malformations occur in the second month of gestation, an external insult, like antibiotics, may affect the development of embryonic structures. While unilateral maldevelopment secondary to an embryonic teratogen is not uncommon, one would more likely expect bilateral ocular abnormalities, especially if the exposure is early in gestation. We also do not know why the levator muscle was affected since its development occurs later than the closure of the fetal fissure and the development of the cornea. Recently, several genetic studies have been done to identify the possible cause of congenital ptosis. Especially, twin studies seem to support the idea of inheritance in these cases. Also, gene mutations like PAX6 mutation or those detected in syndromes such as Ohdo blepharophimosis syndrome and Oculo-facio-cardio-dental syndrome were proposed to be responsible for the presence of congenital ptosis. These rare mutations may help us while evaluating such cases.2,7-9 Although congenital ptosis rarely present with systemic and ocular congenital malformations, the possibility of coexisting structural defects must not be overlooked. References 1. Pallotta R. Iris coloboma, ptosis, hypertelorism, and mental retardation: a new syndrome possibly localized on chromosome 2. J Med Genet 1991;28:342-4. 2. Malandrini A, Mari F, Palmeri S, Gambelli S, Berti G, Brutini M, et al. PAX6 mutation in a family with aniridia, congenital ptosis, and mental retardation. Clin Genet 2001;2001:151-4. 3. Larned DC, Flanagan JC, Nelson LE, Harley RO, Wilson TW, et al. The association of congenital ptosis and congenital heart disease. Ophthalmology 1986;93:492-4. 4. Sadler TW. Langman’s medical embryology. Baltimore: Williams & Wilkins; 1990. pp. 196-8, 266-8, 345. 5. Burns RP, Anderson RS, Feeney-Burns L. Cataract-webbed trait in Peromyscus. II. Biomicroscopy and histology of eyes. Invest Ophthalmol Vis Sci 1980;19:31-41. 6. Salmon JF, Wallis CE, Murray ADN. Variable expressivity of auto-
Journal of AAPOS Volume 8 Number 3 June 2004
Yılmaz, Hos¸al, and Zileliog˜lu
somal dominant microcornea with cataract. Arch Ophthalmol 1988; 106:505-10. 7. Mhanni AA, Dawson AJ, Chudley AE. Vertical transmission of the Ohdo blepharophimosis syndrome. Am J Med Genet 1998;77:144-8. 8. Schulze BR, Horn D, Kobelt A, Tariverdian G, Stellzig A, et al. Rare
295
dental abnormalities seen in oculo-facio-cardio-dental (OFCD) syndrome: three new cases and review of nine patients. Am J Med Genet 1999;82:429-35. 9. Vestal KP, Seiff SR, Lahey JM. Congenital ptosis in monozygotic twins. Opthal Plast Reconstr Surg 1990;6:265-8.
An Eye on the Arts – The Arts on the Eye
I would conquer space by hurtling through it. I wore telescopic glasses, suffered from crushing headaches, but still chose to ride a bicycle—with nothing more than adrenaline for assurance. How do you ride a bicycle when you can’t see? You hold your head like a stiff flower and tilt toward the light. You think not at all about your chances—the sheer physicality of gutters and pavements. One submits to Holy Rule and spins ahead. Picture this: A darkness rises. Is it a tree or a shadow? A shadow or a truck? The thrill of the high wire is the greatest wonder of the brain. There is, at the center of our skulls, a terrible glittering, a requiem light. I lower my face to the cold handlebars and decide it’s a shadow, a hole in sunlight, and pedal straight through. Here’s another shadow, and another. I turn sharply but this time plunge into tall weeds. Insects rise into my hair, cling to my sweaty face. From the road comes the hiss of angered gravel, a car roars past. Thanks be to God! I’m alive in the wild carrot leaf! —Stephen Kuusisto (from Planet of the Blind)