Infantile glaucoma in a patient with Rothmund-Thomson syndrome M. Erol MD; Oya Tekeli, MD R othmund-Thomson syndrome is a rare hereditary syndrome characterized by early onset of poi- kiloderma. Patients exhibit variable features, includ- ing skeletal abnormalities, juvenile cataracts and pho- tosensitivity. The syndrome was first described in 1868 by Rothmund, 1 and in 1923 Thomson 2 described two sisters with similiar findings without cataracts. The syndrome is often associated with ophthalmologic abnormalities. We describe a patient with Rothmund- Thomson syndrome who also had bilateral infantile glaucoma, exotropia and conjunctiva! subepithelial melanosis as well as a cerebrovascular ischemic acci- dent. Our case emphasizes the importance of exact ophthalmologic examination to avoid visual loss in patients with Rothmund-Thomson syndrome, partic- ularly in association with glaucoma. CASE REPORT A 17-year-old girl was admitted to hospital with a history of glaucoma surgery and skin lesions since infancy. The skin rash had begun soon after birth and had spread over several years over her face, ears, neck and arms. We obtained her past ocular history from her parents. Glaucoma had been diagnosed at age 5 years, when she was examined because of strabismus. Her intraocular pressure had been measured at 32 mm Hg in the right eye and 35 mm Hg in the left From the Department of Ophthalmology, Faculty of Medicine, Ankara University, Ankara, Turkey Originally received Aug. 11, 2003 Accepted for publication Apr. 27, 2004 Correspondence to: Prof. Dr. M. Ero! Atatiirk Bui van 177/10 Kavakhdere, Ankara, Turkey; fax +90-312-425 28 29, eturacli@ hotmail.com This article has been peer-reviewed. Can j Ophthalmol 2004;39:674-8 6 74 Rothmund-Thomson syndrome-Tura9h et al eye before her first surgical procedures. Her uncor- rected visual acuity had been measured at 0.2 in the right eye and counting fingers at 3 m in the left eye before and after the procedures. The family did not know the best-corrected visual acuity. The patient had undergone trabeculectomy twice in the right eye and once in the left eye (Fig. 1). She was the first child of consanguineous Turkish parents. There was no family history of glaucoma, and the patient's two siblings were healthy. Her neurodevelopment was normal. Her most recent menstruation had been 3 months before admission. One month before the current admission she had been admitted to the neurology department, where a diagnosis of acute ischemic cerebrovascular accident was made. She was treated with clopidogrel and phenytoin sodium. On ophthalmologic examination the girl's uncor- rected visual acuity was measured at counting fingers at 5 m in the right eye and counting fingers at 3 m in the left eye. Her best-corrected visual acuity was 4110 with -4.0 -0.5 x 180 in the right eye and 2/10 with -6.0 -1.0 x 90 in the left eye. Glaucoma was the main cause of her visual loss. There was 50 prism dioptres of alternating exotropia at near and distance. Her eye movements were normal. There was no loss of hair, eyelashes or eyebrows. Biomicroscopic examination showed conjunctiva! subepithelial melanosis in both eyes and a mild posterior polar cataract in the right eye (Fig. 1). Slit-lamp examination revealed no evi- dence of breaks in Descemet' s membrane or corneal scarring. Both pupils and irises were normal, as were the corneal diameters. The lens was clear in her left eye. The cup-to-disc ratio was 0.9 in both eyes, and the intraocular pressure was 21 mm Hg in the right eye and 23 mm Hg in the left eye. She was not taking any glaucoma medications. Gonioscopy demon- strated grade II angles (Schaffer scale) in both eyes and peripheral anterior synechiae at the 5, 6:30 and 10 o'clock positions in the right eye. There were no apparent anomalies in the chamber angle. Heidelberg
Transcript
Infantile glaucoma in a patient with Rothmund-Thomson syndrome
M. Erol Tura~h, MD; Oya Tekeli, MD
Rothmund-Thomson syndrome is a rare hereditary syndrome characterized by early onset of poi
kiloderma. Patients exhibit variable features, including skeletal abnormalities, juvenile cataracts and photosensitivity. The syndrome was first described in 1868 by Rothmund, 1 and in 1923 Thomson2 described two sisters with similiar findings without cataracts. The syndrome is often associated with ophthalmologic abnormalities. We describe a patient with RothmundThomson syndrome who also had bilateral infantile glaucoma, exotropia and conjunctiva! subepithelial melanosis as well as a cerebrovascular ischemic accident. Our case emphasizes the importance of exact ophthalmologic examination to avoid visual loss in patients with Rothmund-Thomson syndrome, particularly in association with glaucoma.
CASE REPORT
A 17-year-old girl was admitted to hospital with a history of glaucoma surgery and skin lesions since infancy. The skin rash had begun soon after birth and had spread over several years over her face, ears, neck and arms. We obtained her past ocular history from her parents. Glaucoma had been diagnosed at age 5 years, when she was examined because of strabismus. Her intraocular pressure had been measured at 32 mm Hg in the right eye and 35 mm Hg in the left
From the Department of Ophthalmology, Faculty of Medicine, Ankara University, Ankara, Turkey
Originally received Aug. 11, 2003 Accepted for publication Apr. 27, 2004
Correspondence to: Prof. Dr. M. Ero! Tura~h. Atatiirk Bui van 177 /10 Kavakhdere, Ankara, Turkey; fax +90-312-425 28 29, eturacli@ hotmail.com
This article has been peer-reviewed.
Can j Ophthalmol 2004;39:674-8
67 4 Rothmund-Thomson syndrome-Tura9h et al
eye before her first surgical procedures. Her uncorrected visual acuity had been measured at 0.2 in the right eye and counting fingers at 3 m in the left eye before and after the procedures. The family did not know the best-corrected visual acuity. The patient had undergone trabeculectomy twice in the right eye and once in the left eye (Fig. 1). She was the first child of consanguineous Turkish parents. There was no family history of glaucoma, and the patient's two siblings were healthy. Her neurodevelopment was normal. Her most recent menstruation had been 3 months before admission. One month before the current admission she had been admitted to the neurology department, where a diagnosis of acute ischemic cerebrovascular accident was made. She was treated with clopidogrel and phenytoin sodium.
On ophthalmologic examination the girl's uncorrected visual acuity was measured at counting fingers at 5 m in the right eye and counting fingers at 3 m in the left eye. Her best-corrected visual acuity was 4110 with -4.0 -0.5 x 180 in the right eye and 2/10 with -6.0 -1.0 x 90 in the left eye. Glaucoma was the main cause of her visual loss. There was 50 prism dioptres of alternating exotropia at near and distance. Her eye movements were normal. There was no loss of hair, eyelashes or eyebrows. Biomicroscopic examination showed conjunctiva! subepithelial melanosis in both eyes and a mild posterior polar cataract in the right eye (Fig. 1). Slit-lamp examination revealed no evidence of breaks in Descemet' s membrane or corneal scarring. Both pupils and irises were normal, as were the corneal diameters. The lens was clear in her left eye. The cup-to-disc ratio was 0.9 in both eyes, and the intraocular pressure was 21 mm Hg in the right eye and 23 mm Hg in the left eye. She was not taking any glaucoma medications. Gonioscopy demonstrated grade II angles (Schaffer scale) in both eyes and peripheral anterior synechiae at the 5, 6:30 and 10 o'clock positions in the right eye. There were no apparent anomalies in the chamber angle. Heidelberg
Rothmund-Thomson syndrome-Tura<;h et al
Fig. I-Appearance of blebs and conjunctiva! subepithelial melanosis in both eyes (right eye on left, left eye on right) and mild posterior polar cataract in right eye (bottom left).
retina tomograph studies showed marked glaucomatous changes in both optic discs. Visual field testing (Humphrey Field Analyzer 750, central 30-2 threshold test, Humphrey Instruments, San Leandro, Calif.) showed double arcuate defects in the right eye, and a nasal step and a large inferior arcuate defect in the left eye (Fig. 2). A diagnosis of infantile glaucoma (no buphthalmos, no corneal edema or scarring, and no corneal enlargement) was made, and the patient was treated with betaxolol, with a good response.
Cytogenetic evaluation showed a normal karyotype with no evidence of trisomy mosaicism or chromosomal rearrangement. There was no evidence of musculoskeletal disease or growth retardation (she had a history of growth delay in childhood). Her hearing and intelligence were normal.
On dermatologic examination, erythematous macules, reticulate macules and telangiectases were noted over her face, neck, ears and extensor aspects of the hands and arms (Fig. 3). These features were considered by the dermatologist to be consistent with a diagnosis of Rothmund-Thomson syndrome.
The levels of antithrombin III, protein C, protein S, total cholesterol, low-density lipoprotein cholesterol,
very low density lipoprotein cholesterol and triglycerides were within normal limits. The high-density lipoprotein cholesterol concentration was low, at 26 mg/dL (0.70 mmol/L) (normally 40-80 mg/dL [1.05-2.05 mmol/L]). Testing for antinuclear antibodies gave negative results. The lupus anticoagulant level was within normal limits. Resistance to activated protein C, the activated partial thromboplastin time and the prothrombin time were within normal limits, as was the complete blood count. Transesophageal echocardiography and electrocardiography gave normal results. Carotid Doppler sonography showed the presence of nonstenotic atheromatous plaque at the bifurcation of the left carotid artery.
COMMENTS
Poikiloderma is the main distinguishing characteristic of Rothmund-Thomson syndrome. The skin findings usually appear during the third to sixth month of life and progress into adulthood. Other abnormalities are short stature, skeletal abnormalities, sparse hair, hypogonadism, defective dentition, nail dystrophy, hyperkeratosis and mental retardation.3
Fig. 2-Central 30-2 threshold visual field shows double arcuate defects in right eye (top) and nasal step and large inferior arcuate defect in left eye (bottom).
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Fig. 3-Characteristic skin lesions over face, neck, ears, hand and forearm.
The etiology of the syndrome is unknown. A mutation of RECQ4 has been reported in some patients.4 The diagnosis is made on clinical grounds as no laboratory test with consistent results has been identified.
The main inherited conditions due to mutations in DNA repair genes are xeroderma pigmentosum, Cockayne's syndrome, trichothiodystrophy, Bloom syndrome, Rothmund-Thomson syndrome and Werner's syndrome.5 Eyelid skin cancers and retinal dystrophy are the main features of xeroderma pigmentosum and Cockayne's syndrome respectively. In trichothiodystrophy, cataract is the main ophthalmic feature, with mental and physical retardation. Bloom syndrome is characterized by growth deficiency, immunodeficiency and conjunctiva! telangiectasia, and Werner's syndrome is characterized by premature aging, including greying of the hair, often before the age of 20 years.5 These possible etiologic factors were ruled out in our patient given her clinical characteristics.
Rothmund-Thomson syndrome is often associated with ophthalmologic abnormalities, including cataract, corneal anomalies, blue sclera, glaucoma, persistent pupillary membrane, iris stromal hypoplasia, pseudodistichiasis, iris and chorioretinal colobomas, and tapetoretinal degeneration. 6•7 Cataracts tend to develop earlier rather than later. In their cohort of 41 patients with the syndrome, Wang and colleagues8
reported fewer cataracts compared with historical reports.
To our knowledge, two cases of RothmundThomson syndrome in association with glaucoma have previously been reported. Nathanson and associates9
described a patient who had bilateral glaucoma (treated surgically) without cataract, and Lin and coworkers6
described a patient with glaucoma associated with pseudodistichiasis, persistent pupillary membrane and clear lenses. Our patient had a mild posterior polar cataract in the right eye. Depending on whether juvenile cataracts are present, the disorder may be classified as Rothmund-type Rothmund-Thomson syndrome (with cataracts) or Thomson-type Rothmund-Thomson syndrome (without cataracts). Associated manifestations in our patient included conjunctiva! subepithelial melanosis, exotropia and a cerebrovascular ischemic accident.
In conclusion, this report emphasizes the importance of ophthalmic examination in patients with RothmundThomson syndrome. Both internists and ophthalmologists should be alert to the clinical manifestations in order to identify and treat these patients early.
REFERENCES
1. Rothmund A. Ueber Cataracten in Verbindung mit einer eigenthtimlichen Hautdegeneration. Graef es Arch Ophthalmol I 868; I 4: 159-82.
3. Piquero-Casals J, Okubo AY, Nico MM. RothmundThomson syndrome in three siblings and development of cutaneous squamous cell carcinoma. Pediatr Dermatol 2002;19(4):312-6.
4. Balraj P, Concannon P, Jamal R, Beghini A, Hoe TS, Khoo AS, et al. An unusual mutation in RECQ4 gene leading to Rothmund-Thomson syndrome. Mutat Res 2002;508(1-2):99-105.
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5. Dollfus H, Porto F, Caussade P, Speeg-Schatz C, Sahel J, Grosshans E, et al. Ocular manifestations in the inherited DNA repair disorders. Surv Ophthalmol 2003;48(1): 107-22.
6. Lin C, Lueder GT, Kass MA. Ocular abnormalities in a patient with Rothmund-Thomson syndrome. J Pediatr Ophthalmol Strabismus 1995;32(2):132-4.
7. Collins P, Barnes L, McCabe M. Poikiloderma congenitale: case report and review of the literature. Pediatr Dermatol 1991;8(1):58-60.
8. Wang LL, Levy ML, Lewis RA, Chintagumpala MM, Lev D, Rogers M, et al. Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients. Am J Med Genet 2001;102(1):11-7.
9. Nathanson M, Dandine M, Gaudelus J, Mousset S, Lasry D, Perelman R. [Rothmund-Thomson syndrome with glaucoma. Endocrine study.] Sem Hop 1983;59(48): 3379-84.
