A boy with Dubowitz syndrome presented with a progressive X-pattern exotropia at 9 years of age. He subsequently developed nuclear cataracts at age 12.
The Dubowitz syndrome is a rare, autosomal, recessiveIy inherited disorder of intrauterine and postnatal growth retardation. Patients exhibit microcephaly, mental retardation, hyperactivity, eczema, brachyclinodactyly, and characteristic facial anomalies. The facial anomalies include: telecanthus, epicanthal folds, blepharophimosis, ptosis, broad nasal bridge and tip of the nose, abnormal ears, and retrognathia. Additionally, male patients may have cryptorchidism. 1-6
We present this case to emphasize the importance of strabismus and cataracts in this syndrome. In the past, strabismus has been underemphasized, and cataracts have never been reported in Dubowitz syndrome.
Fig 1: This 9-year-old boy presented with mental retardation, short stature, and Xpattern exotropia.
JSC was born at term to a 20-year-old gravida-1, para-0, abortion-0 mother after an uncomplicated pregnancy and deUvery. Mother reported no viral or other systemic illness or teratogen exposure during the pregnancy. The infant's birth weight was .9375 kg (<3rd percentile). Apgar scores were 5 and 8 at 1 and 5 minutes, respectively. He remained in the nursery for 3 months as a result of poor weight gain.
Within the first 6 months of life, he was suspected of having an immune deficiency because of the occurrence of osteomyelitis and recurrent bouts of otitis media. The patient was given intravenous (IV) gammaglobulin, which resolved the problem. Chromosome studies revealed a gbanded, 46,XY karyotype at the 400-band stage.
On physical examination, this 9-year-old boy functioned in the severe range of mental retardation. He could feed and dress himself, and signed approximately 30 words. His height was 106 cm (50th percentile, 4Ve years); he weighed 11.9 kg (50th percentile, 18 months); his head circumference was 40 cm (50th percentile, 12 months); his upperlower segment ratio was .90 (15th percentile); and his arm span was 102 cm (consistent with height) (Fig 1). Craniofacial findings included: microcephaly with occipital flattening, platybasa, shallow supraorbital ridges, and shaUow orbits. Relative hypertelorism (outer canthus to outer canthus 9.5 cm [95th percentile]) was noted and unilateral ptosis with upslanted palpebral fissures. The ears were at the 50th percentile for size at 9 months with decreased cartilage and underformed helices, antiheUces, and tragus. The patient's nose was small with a wide nasal bridge, hypoplastic alae nasi, and a depressed tip. There was malar flattening and facial asymmetry. He had gum hypertrophy, a high-arched palate, and irregular, immature, carious teeth (Fig 2).
Fig 2: A 9-year-old boy with Dubowitz syndrome with dental anomalies, hypertelorism, and unilateral ptosis.
Clinical Findings in Dubowitz Syndrome
Chest measurements were at the 50th percentile for age 2. No pulmonary or cardiovascular abnormaUties were found. Genitourinary examination found him to be Tanner stage 1 with a Io hypospadias. He had a 20° midthoracic scoUosis and a 10° kyphosis. Hand size was 50th percentile for 4 years with brachycUnodactyly and proximally placed thumbs. Generalized limitation of joint mobility was present. An ichthyotic rash was generalized. Musculature was decreased and neurologic examination was without localized signs.
A chest X-ray obtained demonstrated gastroesophageal reflux, mild thoracic levoscoliosis, and extremely small size for the age of 9.
Ocular History and Examination
The patient's first documented ocular examination was at age 5. Visual acuity revealed no fixation preference or gross amblyopia signs. There was moderate telecanthus (inner canthus to inner canthus, 3.4 cm [95th percentile]). Pupils were equal, round, and reactive. Motility examination demonstrated a 16-prism-diopter (?) alternative exotropia. No lenticular opacities were observed. Fundus examination was normal. Cycloplegic retinoscopy revealed +0.75 sphere OU.
A worsening of his exotropia was noted over the next 4 years. Motility examination revealed an X-pattern exotropia with 75 ? in the primary position. This increased in upgaze to 90 ? and 80 ? on downgaze. Versions demonstrated both 4+ overaction of the superior obliques and 4+ overaction of the inferior obliques. Strabismus surgery was performed at age 9 (bilateral 9-mm lateral rectus recession with an 8-mm resection of the right medial rectus) with good results. Postoperative alignment at 3 months demonstrated 8 ? of exotropia in primary position, upgaze, and downgaze. He was followed every 3 months thereafter.
Examination at age 12 showed a dense, primarily nuclear cataract in the left eye. The right eye demonstrated posterior subcapsular and nuclear opacification. Phacofragmentation of both cataracts was performed 2 months apart. The patient was fitted with aphakic extended-wear contact lenses and has maintained good central visual acuity and stabilization of motility to 6 ? of exotropia.
The patient's clinical findings are consistent with the diagnosis of Dubowitz syndrome (Tables 1, 2). Significant clinical correlation includes: smaU stature, microcephaly, abnormal ears, ptosis, hypertelorism, wide nasal bridge, dental malocclusion, eczema, and mental retardation. Associations have been made with hyperactivity (4G" variable clefts of the soft palate (10% to 15%), poor feeding and gastroesophageal reflux (33%), chronic diarrhea (35%), and mild eczema (65%)7. Additionally, vascular accidents,8 hematologic malignancies,9"10 and aplastic anemia11'12 have been noted.
Ophthalmologic Findings In Dubowitz Syndrome
Our patient exhibited mental retardation but no hyperactivity. He had gastroesophageal reflux and chronic eczema with ichthyotic changes, but no chronic diarrhea. This patient had chronic infections with an immunodeficiency similar to previously reported cases.2"4·10 There is currently no clear delineation of the immunodeficiency.
The ophthalmologic findings of telecanthus, epicanthal folds, ptosis, and blepharophimosis have been well documented in the Dubowitz syndrome.7 Cases of persistent hyperplastic primary vitreous and pigmentary retinopathy,8 microphthalmia, and convolution of retinal vessels have been described (Table 2).
Four cases of strabismus have been reported.3·6,13'14 This, however, is the first documented case of a progressive Xpattern exotropia and cataracts in a patient with the Dubowitz syndrome. The etiology of the cataracts is unknown, but the surface ectodermal derivation of the lens may point to the possibility of a gene related to connective tissue formation or regulation. We recommend that patients with Dubowitz syndrome be monitored routinely for both the development of strabismus and cataracts.
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Clinical Findings in Dubowitz Syndrome
Ophthalmologic Findings In Dubowitz Syndrome