138
Short case report
Ocular anomalies in Rubinstein–Taybi syndrome: a further case report and review of the literature Sukru Candana, Cigdem Ornekb and Feride Candanc Clinical Dysmorphology 2014, 23:138–142 a
Tel: + 90 266 2213510; fax: + 90 266 2213516; e-mail: [email protected]
b
Departments of Medical Genetics, Ophtalmology, Balikesir Ataturk State Hospital and cDepartment of Neurology, Balikesir State Hospital, Balikesir, Turkey
Received 24 July 2013 Accepted 17 June 2014
Correspondence to Sukru Candan, MD, Department of Medical Genetics, Balikesir Ataturk State Hospital, 10100 Balikesir, Turkey
List of key features Early onset congenital glaucoma Coloboma Convex beaked nose with columella below alae nasi Dental crowding, abnormal shape teeth with talon cusp Characteristic grimace with closure of eyes Broad radially deviated thumb, broad great toes Preauricular pits Mental retardation
Introduction Rubinstein–Taybi syndrome (RSTS1; OMIM 180849, RSTS2; 613684) was first described in 1963 (Rubinstein and Taybi). It is an autosomal dominant congenital disease with a birth prevalance of around 1/100 00–1/125 000 (Hennekam et al., 1990). This rare genetic syndrome is characterized by distinctive facial dysmorphism, microcephaly, short stature, moderate to severe intellectual impairment, and distinctive broad thumbs and toes that are frequently medially angulated. The characteristic facial features are high arched eyebrows, downslanting palpebral fissures, ptosis, epicanthic folds, a low columella, high arched palate, and dental abnormalities. Patients with RSTS often have a normal birth weight and head circumference, but these quickly decrease from their original percentiles in the first few months of life, resulting in short stature in adulthood (Hennekam, 2006). Average intelligence quotient (IQ) is between 35 and 50, but motor and mental development varies and IQ is substantially higher in some cases. Individuals with RSTS usually have good social skills (Hennekam et al., 1992). Feeding difficulties and sleep apnea are common. RSTS can be associated with a number of medical complications including those involving the eye, skeleton, genitourinary system, and heart (Hennekam, 2006). Mutations in CREBBP and EP300 have been described in association with RSTS. DNA analysis can identify a mutation in one of these two genes in ∼ 60% of all cases (Negri et al., 2014). At present, in the remaining half of patients, the cause of RSTS remains unknown (Roelfsema and Peters, 2007). RSTS typically occurs as a consequence of the de-novo mutation in a family, although rare familial 0962-8827 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
cases have been seen. Diagnosis during the neonatal period can be difficult but is facilitated by the recognition of characteristic broadening of the distal phalanges of thumbs and great toes and facial abnormalities, which become more distinct as the child becomes older (Hennekam et al., 1992; Hennekam, 2006). Extraocular and intraocular anomalies are common, occurring in about 50–80% of cases. Extraocular features described in the literature include hypertelorism, high arched eyebrows, downslanting palpebral fissures, epicanthic folds, ptosis, long eyelashes, and nasolacrimal duct stenosis. Congenital intraocular anomalies of different types are seen in more than half of RSTS patients. Ocular features include strabismus, nystagmus, refractive errors, cataracts, coloboma (involving the iris, retina, or optic nerve), corneal abnormalities, congenital cataract, iris atrophy, high myopia and other refractor anomalies, and congenital glaucoma (Quaranta and Quaranta, 1998; Van Genderen et al., 2000). Here, we further present a RSTS patient with various eye anomalies including early onset severe glaucoma and a review of the literature on this topic.
Case report A 13-year-old girl patient was referred to our Medical Genetics department because of an abnormal facial appearance and unusual fingers. Her mother was pregnant at the time and recurrence risk was being queried. She was born at term to a couple who are second cousins. Her birth weight was 2.6 kg (third percentile). Birth length and birth head circumference were unavailable. At birth, she had suffered from respiratory distress and had been noted to have a right pes valgus and the right eye slightly bigger than the left. Her developmental milestones had been globally delayed and she had a significant learning disability with an IQ of 31. She had had frequent recurrent otitis until she was 5 years of age and an obvious frontal capillary hemangioma until she was 2 years of age. In addition, she had begun to eat voraciously when she was 9 years of age and she was overweight for her height. On examination, her height was 140 cm (< 3rd percentile), weight was 52 kg (75–90th percentile), and head circumference was 51 cm (25–50th DOI: 10.1097/MCD.0000000000000047
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Ocular anomalies in Rubinstein–Taybi syndrome Candan et al. 139
Fig. 1
Face in RSTS case: she has classical facial dysmorphic features and (b) side view of face and characteristic grimace smiling in RSTS. RSTS, Rubinstein–Taybi syndrome.
Fig. 2
These photographs show hair, teeth, and skin signs. Low occipital hairline (a), high and narrow arched palate and dental crowding (b), talon cusp (c), bilateral preauricular pits in the crus of helix (d, e), nevus in the back (f), plantar crease between the first and second toes and pes planus (g), redundant palmar skin and deep palmar crease and persistent finger pads (h).
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
140 Clinical Dysmorphology
2014, Vol 23 No 4
Fig. 3
Photographs and radiographs of hands and feet. Broad thumbs and angulations (a, c) and broad toes are remarkable (b, d).
percentile). She had the characteristic facial dysmorphism and facial grimacing seen in RSTS (Fig. 1). Her distinctive features included low-set ears, hypertelorism, high arched eyebrows, ptosis, downslanting palpebral fissures, inner epicanthal folds, convex beaked nose, low and thick columella, thin upper lip, a protuberant lower lip, small opening of the mouth, grimacing smile with almost closed eyes on smiling, and a high and narrow arched palate. She had dental crowding and abnormally shaped teeth with a talon cusp. She had a low occipital hairline, slight hirsutism especially on the back and extensor side of the arms, bilateral preauricular pits on the crus of the helix, and 2 × 1.5 cm nevus on her back (Fig. 2). She had broad thumbs that were radially deviated, persistent fetal finger pads, and broad great toes (Fig. 3). In her right eye, ectopia lentis was noted, and the right eyeball was bigger than the left due to glaucoma. She had a cataract in the lens, corneal clouding, retinal coloboma (6 o’clock), and no light reflex. In the left eye, she had an iris coloboma (7 o’clock) and a retinal coloboma (6 o’clock) (Fig. 4). Cardiac echo, abdominal ultrasound scan, cranial MRI, and metabolic tests did not detect any anomalies.
Discussion RSTS is very rare congenital syndrome that has been well defined in the literature. It is characterized by facial
dysmorphism and broad thumbs and toes (Rubinstein et al., 1963; Hennekam et al., 1990). In addition, it results in short stature and intellectual disability. Ocular, cardiac, and genitourinary anomalies, skeletal anomalies, dental anomalies, skin abnormalities, central nervous anomalies, and immunologic deficits can be seen (Hennekam, 2006). Ocular problems are very frequent in RSTS, ∼ 80% of cases having extraocular or intraocular features (Brei et al., 1995; Van Genderen et al., 2000). The most serious and the one that requires early diagnosis and treatment is glaucoma. Early diagnosis and treatment is essential to safeguard vision. Late diagnosis and treatment can result in blindness or much reduced vision as in our case. In our patient, although a difference in the size of the eyes had been noted at birth, no regular ophthalmological followup had been arranged. Glaucoma is detected as high as 15% in the literature that we have consulted. However, this result may be higher due to missed diagnosis or insufficient ophthalmological follow-up (Table 1). In addition, strabismus, lacrimal problems, and refractor anomaly are detected as the most frequent anomalies. The first reports of glaucoma with respect to RSTS were described in the literature in 1968 (Blanck et al., 1968), and successful treatment of unilateral congenital glaucoma with trabeculotomy was reported in 1985 (Bardelli et al., 1985). A large review of clinical findings in 614
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Ocular anomalies in Rubinstein–Taybi syndrome Candan et al. 141
Fig. 4
Extraocular and intraocular findings: hypertelorism, bilateral epicanthal folds, downslanting palpebral fissures, long eyelashes and the right eyeball bigger than the left eyeball (a), fully dilated pupil and deleted iris (buphthalmic eye) (b), and iris coloboma in the left eye (c).
Table 1
Frequency of ocular symptoms in patients with Rubinstein–Taybi syndrome in the literature
Symptoms
Our patient
Strabismus
–
68
Refractor anomalies
–
42
Lacrimal duct problems Glaucoma/intraocular high pressure
– +
30 15
Corneal abnormalities Chorioretinal dystrophy Cataract Optic atrophy/optic disc abnormalities Coloboma (iris, cornea, retinal) Nystagmus Iris abnormalities Microcornea/microphthalmia/enophtalmia Pupillary abnormalities Lentis abnormalities
+ Unknown + – + – – – – +
Rate (%)
12 9 8.5 6.8 5.4 4.2 3.4 3.3 1.4 1.4
References Kumar et al. (2012); Negri et al. (2014); Da Costa and Brookes (2012); Van Genderen et al. (2000)a,b Bansal et al. (2013); Negri et al. (2014); Da Costa and Brookes (2012); Van Genderen et al. (2000); Siraganian et al. (1989)a,b Kumar et al. (2012); Marabotti et al. (2002); Van Genderen et al. (2000)a,b Kosaki et al. (2011); Da Costa and Brookes (2012); Van Genderen et al. (2000)b; Wieczorek et al. (2009) Kumar et al. (2012); Da Costa and Brookes (2012); Rao et al. (2002); Van Genderen et al. (2000)b Jacobs et al. (2012); Van Genderen et al. (2000) Van Genderen et al. (2000)b Van Genderen et al. (2000) Van Genderen et al. (2000)b Da Costa and Brookes (2012); Van Genderen et al. (2000) Da Costa and Brookes (2012); Rao et al. (2002); Van Genderen et al. (2000)b Da Costa and Brookes (2012); Van Genderen et al. (2000) Van Genderen et al. (2000) Da Costa and Brookes (2012); Van Genderen et al. (2000)
Van Genderen et al.’s (2000) article has also referred Rubinsteina and Stevensb RSTS patient series, number of 571 and 50 patients, respectively.
patients with RSTS reported glaucoma in 32 cases and corneal opacities in 25 cases. This same article on glaucoma described some other ocular anomalies such as corneal lesions, megalocornea, a colobomatous or cystic optic nerve, excavation of papilla, and large cup-to-disc ratio (Brei et al., 1995). Ocular examination to search for all of these would therefore seem to be recommended.
A further case series of 24 patients with RSTS included one patient who had bilateral buphthalmos (4%) and three patients who had increased intraocular pressures (12%). Surprisingly, macular anomalies were detected in 75% of cases, and a high frequency of retinal dysfunction on ERG was also documented (Van Genderen et al., 2000). Glaucoma was recognized in most patients due to
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
142 Clinical Dysmorphology
2014, Vol 23 No 4
detection of enlargement of one or both eyes. Treatment for glaucoma is usually the same as for other patients with glaucoma. Quaranta and Quaranta (1998) observed normalization of intraocular pressure, improved appearance of the head of the optic nerve, and reduced pallor of the disc using interno goniotrabeculotomy. Congenital glaucoma can be seen in the infantile term of RSTS cases. Da Costa and Brookes (2012) reported three patients with RSTS who had raised intraocular pressure and glaucoma; two of them were 5 months of age and one was 4 months of age. Keloid formation can be seen after operation, trauma, and also congenital in RSTS patients’ skin (Siraganian et al., 1989; Bansal et al., 2013). Our patient has only preauricular pits, slight hirsutism, and largish nevus as skin abnormalities. Similarly, a further ocular abnormality seen in RSTS is corneal keloid formation. Bilateral corneal keloids and anterior segment mesenchymal dysgenesis were reported in a 2-year-old male child with RSTS. Bilateral corneal opacities had been noted at 4 months of age and after operation, recurrence of a right keloid can result in multiple recurrences (Rao et al., 2002). Our patient does not have history of surgery nor injury, and we did not detect any keloid formation on her skin. Up to date, congenital keloid related to eyes in patients with RSTS has not been reported. The clinical diagnosis of RSTS can be relatively easy, if the characteristic features are present, but following diagnosis it is important to rule out associated anomalies such as cardiac and renal defects. It is particularly important also to rule out the ocular complications of the condition by requesting a detailed ophthalmological examination following diagnosis with annual ophthalmic review for the first few years of life. Congenital glaucoma and cataracts are preventable causes of blindness and early treatment is essential. Unfortunately, our patient lost vision from her right eye due to delayed diagnosis and treatment of glaucoma.
Acknowledgements Conflicts of interest
There are no conflicts of interest.
References Bansal S, Relhan V, Garg VK (2013). Rubinstein–Taybi syndrome: a report of two siblings with unreported cutaneous stigmata. Indian J Dermatol Venereol Leprol 79:714–717. Bardelli AM, Lasorella G, Barberi L, Vanni M (1985). Ocular manifestations in Kniest syndrome, Smith-Lemli-Opitz syndrome, Hallermann-Streiff-Francois syndrome, Rubinstein–Taybi syndrome and median cleft face syndrome. Ophthalmic Paediatr Genet 6:103–107. Blanck MF, Braun-Vallon S, Guillaumat ML (1968). 2 cases constitutional dwarfism (Rubinstein-Taybi syndrome) with glaucoma. Bull Soc Ophtalmol Fr 68:173–176. Brei TJ, Burke MJ, Rubinstein JH (1995). Glaucoma and findings simulating glaucoma in the Rubinstein–Taybi syndrome. J Pediatr Ophthalmol Strabismus 32:248–252. Da Costa J, Brookes J (2012). Infantile glaucoma in Rubinstein–Taybi syndrome. Eye (Lond) 26:1270–1271. Hennekam RC (2006). Rubinstein–Taybi syndrome. Eur J Hum Genet 14:981–985. Hennekam RC, Stevens CA, Van de Kamp JJ (1990). Etiology and recurrence risk in Rubinstein–Taybi syndrome. Am J Med Genet Suppl 6:56–64. Hennekam RCM, Baselier JCA, Beyaert E, Bos A, Blok JB, Jansma HB, et al. (1992). Psychological and speech studies in Rubinstein–Taybi syndrome. Am J Ment Retard 96:645–660. Jacobs DJ, Sein J, Berrocal AM, Grajewski AL, Hodapp E (2012). Fluorescein angiography findings in a case of Rubinstein–-Taybisyndrome. Clin Ophthalmol 6:1369–1371. Kosaki R, Fujita H, Takada H, Okada M, Torii C, Kosaki K (2011). Monozygotic twins of Rubinstein–Taybi syndrome discordant for glaucoma. Am J Med Genet A 155A:1189–1191. Kumar S, Suthar R, Panigrahi I, Marwaha RK (2012). Rubinstein–Taybi syndrome: clinical profile of 11 patients and review of literature. Indian J Hum Genet 18:161–166. Marabotti A, Giannecchini G, Cariello A, Cappelli C, Giannecchini I, Bedei A (2002). Stenosis of the lachrymal system in Rubinstein–Taybi syndrome. Ophthalmologica 216:272–276. Negri G, Milani D, Colapietro P, Forzano F, Della Monica M, Rusconi D, et al. (2014). Clinical and molecular characterization of Rubinstein–Taybi syndrome patients carrying distinct novel mutations of the EP300 gene. Clin Genet 29:12348. Quaranta L, Quaranta CA (1998). Congenital glaucoma associated with Rubinstein Taybi syndrome. Acta Ophthalmol Scand 76:112–113. Rao SK, Fan DS, Pang CP, Li WW, Ng JS, Good WV, Lam DS (2002). Bilateral congenital corneal keloids and anterior segment mesenchymal dysgenesis in a case of Rubinstein–Taybi syndrome. Cornea 21:126–130. Roelfsema JH, Peters DJ (2007). Rubinstein–Taybi syndrome: clinical and molecular overview. Expert Rev Mol Med 9:1–16. Rubinstein JH, Taybi H (1963). Broad thumbs and toes and facial abnormalities. A possible mental retardation syndrome. Am J Dis Child 105:588–608. Siraganian PA, Rubinstein JH, Miller RW (1989). Keloids and neoplasms in the Rubinstein–Taybi syndrome. Med Pediatr Oncol 17:485–491. Van Genderen MM, Kinds GF, Riemslag FCC, Hennekam RCM (2000). Ocular features in Rubinstein–Taybi syndrome: investigation of 24 patients and review of the literature. Br J Ophthalmol 84:1177–1184. Wieczorek D, Bartsch O, Lechno S, Kohlhase J, Peters DJ, Dauwerse H, et al. (2009). Two adults with Rubinstein–Taybi syndrome with mild mental retardation, glaucoma, normal growth and skull circumference, and camptodactyly of third fingers. Am J Med Genet A 149A:2849–2854.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Short case report
Ocular anomalies in Rubinstein–Taybi syndrome: a further case report and review of the literature Sukru Candana, Cigdem Ornekb and Feride Candanc Clinical Dysmorphology 2014, 23:138–142 a
Tel: + 90 266 2213510; fax: + 90 266 2213516; e-mail: [email protected]
b
Departments of Medical Genetics, Ophtalmology, Balikesir Ataturk State Hospital and cDepartment of Neurology, Balikesir State Hospital, Balikesir, Turkey
Received 24 July 2013 Accepted 17 June 2014
Correspondence to Sukru Candan, MD, Department of Medical Genetics, Balikesir Ataturk State Hospital, 10100 Balikesir, Turkey
List of key features Early onset congenital glaucoma Coloboma Convex beaked nose with columella below alae nasi Dental crowding, abnormal shape teeth with talon cusp Characteristic grimace with closure of eyes Broad radially deviated thumb, broad great toes Preauricular pits Mental retardation
Introduction Rubinstein–Taybi syndrome (RSTS1; OMIM 180849, RSTS2; 613684) was first described in 1963 (Rubinstein and Taybi). It is an autosomal dominant congenital disease with a birth prevalance of around 1/100 00–1/125 000 (Hennekam et al., 1990). This rare genetic syndrome is characterized by distinctive facial dysmorphism, microcephaly, short stature, moderate to severe intellectual impairment, and distinctive broad thumbs and toes that are frequently medially angulated. The characteristic facial features are high arched eyebrows, downslanting palpebral fissures, ptosis, epicanthic folds, a low columella, high arched palate, and dental abnormalities. Patients with RSTS often have a normal birth weight and head circumference, but these quickly decrease from their original percentiles in the first few months of life, resulting in short stature in adulthood (Hennekam, 2006). Average intelligence quotient (IQ) is between 35 and 50, but motor and mental development varies and IQ is substantially higher in some cases. Individuals with RSTS usually have good social skills (Hennekam et al., 1992). Feeding difficulties and sleep apnea are common. RSTS can be associated with a number of medical complications including those involving the eye, skeleton, genitourinary system, and heart (Hennekam, 2006). Mutations in CREBBP and EP300 have been described in association with RSTS. DNA analysis can identify a mutation in one of these two genes in ∼ 60% of all cases (Negri et al., 2014). At present, in the remaining half of patients, the cause of RSTS remains unknown (Roelfsema and Peters, 2007). RSTS typically occurs as a consequence of the de-novo mutation in a family, although rare familial 0962-8827 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
cases have been seen. Diagnosis during the neonatal period can be difficult but is facilitated by the recognition of characteristic broadening of the distal phalanges of thumbs and great toes and facial abnormalities, which become more distinct as the child becomes older (Hennekam et al., 1992; Hennekam, 2006). Extraocular and intraocular anomalies are common, occurring in about 50–80% of cases. Extraocular features described in the literature include hypertelorism, high arched eyebrows, downslanting palpebral fissures, epicanthic folds, ptosis, long eyelashes, and nasolacrimal duct stenosis. Congenital intraocular anomalies of different types are seen in more than half of RSTS patients. Ocular features include strabismus, nystagmus, refractive errors, cataracts, coloboma (involving the iris, retina, or optic nerve), corneal abnormalities, congenital cataract, iris atrophy, high myopia and other refractor anomalies, and congenital glaucoma (Quaranta and Quaranta, 1998; Van Genderen et al., 2000). Here, we further present a RSTS patient with various eye anomalies including early onset severe glaucoma and a review of the literature on this topic.
Case report A 13-year-old girl patient was referred to our Medical Genetics department because of an abnormal facial appearance and unusual fingers. Her mother was pregnant at the time and recurrence risk was being queried. She was born at term to a couple who are second cousins. Her birth weight was 2.6 kg (third percentile). Birth length and birth head circumference were unavailable. At birth, she had suffered from respiratory distress and had been noted to have a right pes valgus and the right eye slightly bigger than the left. Her developmental milestones had been globally delayed and she had a significant learning disability with an IQ of 31. She had had frequent recurrent otitis until she was 5 years of age and an obvious frontal capillary hemangioma until she was 2 years of age. In addition, she had begun to eat voraciously when she was 9 years of age and she was overweight for her height. On examination, her height was 140 cm (< 3rd percentile), weight was 52 kg (75–90th percentile), and head circumference was 51 cm (25–50th DOI: 10.1097/MCD.0000000000000047
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Ocular anomalies in Rubinstein–Taybi syndrome Candan et al. 139
Fig. 1
Face in RSTS case: she has classical facial dysmorphic features and (b) side view of face and characteristic grimace smiling in RSTS. RSTS, Rubinstein–Taybi syndrome.
Fig. 2
These photographs show hair, teeth, and skin signs. Low occipital hairline (a), high and narrow arched palate and dental crowding (b), talon cusp (c), bilateral preauricular pits in the crus of helix (d, e), nevus in the back (f), plantar crease between the first and second toes and pes planus (g), redundant palmar skin and deep palmar crease and persistent finger pads (h).
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
140 Clinical Dysmorphology
2014, Vol 23 No 4
Fig. 3
Photographs and radiographs of hands and feet. Broad thumbs and angulations (a, c) and broad toes are remarkable (b, d).
percentile). She had the characteristic facial dysmorphism and facial grimacing seen in RSTS (Fig. 1). Her distinctive features included low-set ears, hypertelorism, high arched eyebrows, ptosis, downslanting palpebral fissures, inner epicanthal folds, convex beaked nose, low and thick columella, thin upper lip, a protuberant lower lip, small opening of the mouth, grimacing smile with almost closed eyes on smiling, and a high and narrow arched palate. She had dental crowding and abnormally shaped teeth with a talon cusp. She had a low occipital hairline, slight hirsutism especially on the back and extensor side of the arms, bilateral preauricular pits on the crus of the helix, and 2 × 1.5 cm nevus on her back (Fig. 2). She had broad thumbs that were radially deviated, persistent fetal finger pads, and broad great toes (Fig. 3). In her right eye, ectopia lentis was noted, and the right eyeball was bigger than the left due to glaucoma. She had a cataract in the lens, corneal clouding, retinal coloboma (6 o’clock), and no light reflex. In the left eye, she had an iris coloboma (7 o’clock) and a retinal coloboma (6 o’clock) (Fig. 4). Cardiac echo, abdominal ultrasound scan, cranial MRI, and metabolic tests did not detect any anomalies.
Discussion RSTS is very rare congenital syndrome that has been well defined in the literature. It is characterized by facial
dysmorphism and broad thumbs and toes (Rubinstein et al., 1963; Hennekam et al., 1990). In addition, it results in short stature and intellectual disability. Ocular, cardiac, and genitourinary anomalies, skeletal anomalies, dental anomalies, skin abnormalities, central nervous anomalies, and immunologic deficits can be seen (Hennekam, 2006). Ocular problems are very frequent in RSTS, ∼ 80% of cases having extraocular or intraocular features (Brei et al., 1995; Van Genderen et al., 2000). The most serious and the one that requires early diagnosis and treatment is glaucoma. Early diagnosis and treatment is essential to safeguard vision. Late diagnosis and treatment can result in blindness or much reduced vision as in our case. In our patient, although a difference in the size of the eyes had been noted at birth, no regular ophthalmological followup had been arranged. Glaucoma is detected as high as 15% in the literature that we have consulted. However, this result may be higher due to missed diagnosis or insufficient ophthalmological follow-up (Table 1). In addition, strabismus, lacrimal problems, and refractor anomaly are detected as the most frequent anomalies. The first reports of glaucoma with respect to RSTS were described in the literature in 1968 (Blanck et al., 1968), and successful treatment of unilateral congenital glaucoma with trabeculotomy was reported in 1985 (Bardelli et al., 1985). A large review of clinical findings in 614
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Ocular anomalies in Rubinstein–Taybi syndrome Candan et al. 141
Fig. 4
Extraocular and intraocular findings: hypertelorism, bilateral epicanthal folds, downslanting palpebral fissures, long eyelashes and the right eyeball bigger than the left eyeball (a), fully dilated pupil and deleted iris (buphthalmic eye) (b), and iris coloboma in the left eye (c).
Table 1
Frequency of ocular symptoms in patients with Rubinstein–Taybi syndrome in the literature
Symptoms
Our patient
Strabismus
–
68
Refractor anomalies
–
42
Lacrimal duct problems Glaucoma/intraocular high pressure
– +
30 15
Corneal abnormalities Chorioretinal dystrophy Cataract Optic atrophy/optic disc abnormalities Coloboma (iris, cornea, retinal) Nystagmus Iris abnormalities Microcornea/microphthalmia/enophtalmia Pupillary abnormalities Lentis abnormalities
+ Unknown + – + – – – – +
Rate (%)
12 9 8.5 6.8 5.4 4.2 3.4 3.3 1.4 1.4
References Kumar et al. (2012); Negri et al. (2014); Da Costa and Brookes (2012); Van Genderen et al. (2000)a,b Bansal et al. (2013); Negri et al. (2014); Da Costa and Brookes (2012); Van Genderen et al. (2000); Siraganian et al. (1989)a,b Kumar et al. (2012); Marabotti et al. (2002); Van Genderen et al. (2000)a,b Kosaki et al. (2011); Da Costa and Brookes (2012); Van Genderen et al. (2000)b; Wieczorek et al. (2009) Kumar et al. (2012); Da Costa and Brookes (2012); Rao et al. (2002); Van Genderen et al. (2000)b Jacobs et al. (2012); Van Genderen et al. (2000) Van Genderen et al. (2000)b Van Genderen et al. (2000) Van Genderen et al. (2000)b Da Costa and Brookes (2012); Van Genderen et al. (2000) Da Costa and Brookes (2012); Rao et al. (2002); Van Genderen et al. (2000)b Da Costa and Brookes (2012); Van Genderen et al. (2000) Van Genderen et al. (2000) Da Costa and Brookes (2012); Van Genderen et al. (2000)
Van Genderen et al.’s (2000) article has also referred Rubinsteina and Stevensb RSTS patient series, number of 571 and 50 patients, respectively.
patients with RSTS reported glaucoma in 32 cases and corneal opacities in 25 cases. This same article on glaucoma described some other ocular anomalies such as corneal lesions, megalocornea, a colobomatous or cystic optic nerve, excavation of papilla, and large cup-to-disc ratio (Brei et al., 1995). Ocular examination to search for all of these would therefore seem to be recommended.
A further case series of 24 patients with RSTS included one patient who had bilateral buphthalmos (4%) and three patients who had increased intraocular pressures (12%). Surprisingly, macular anomalies were detected in 75% of cases, and a high frequency of retinal dysfunction on ERG was also documented (Van Genderen et al., 2000). Glaucoma was recognized in most patients due to
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
142 Clinical Dysmorphology
2014, Vol 23 No 4
detection of enlargement of one or both eyes. Treatment for glaucoma is usually the same as for other patients with glaucoma. Quaranta and Quaranta (1998) observed normalization of intraocular pressure, improved appearance of the head of the optic nerve, and reduced pallor of the disc using interno goniotrabeculotomy. Congenital glaucoma can be seen in the infantile term of RSTS cases. Da Costa and Brookes (2012) reported three patients with RSTS who had raised intraocular pressure and glaucoma; two of them were 5 months of age and one was 4 months of age. Keloid formation can be seen after operation, trauma, and also congenital in RSTS patients’ skin (Siraganian et al., 1989; Bansal et al., 2013). Our patient has only preauricular pits, slight hirsutism, and largish nevus as skin abnormalities. Similarly, a further ocular abnormality seen in RSTS is corneal keloid formation. Bilateral corneal keloids and anterior segment mesenchymal dysgenesis were reported in a 2-year-old male child with RSTS. Bilateral corneal opacities had been noted at 4 months of age and after operation, recurrence of a right keloid can result in multiple recurrences (Rao et al., 2002). Our patient does not have history of surgery nor injury, and we did not detect any keloid formation on her skin. Up to date, congenital keloid related to eyes in patients with RSTS has not been reported. The clinical diagnosis of RSTS can be relatively easy, if the characteristic features are present, but following diagnosis it is important to rule out associated anomalies such as cardiac and renal defects. It is particularly important also to rule out the ocular complications of the condition by requesting a detailed ophthalmological examination following diagnosis with annual ophthalmic review for the first few years of life. Congenital glaucoma and cataracts are preventable causes of blindness and early treatment is essential. Unfortunately, our patient lost vision from her right eye due to delayed diagnosis and treatment of glaucoma.
Acknowledgements Conflicts of interest
There are no conflicts of interest.
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