Incontinentia pigmenti achromians, or hypomelanosis of Ito, is a multisystem hereditary disorder characterized by a peculiar leukoderma of the skin randomly distributed on the trunk and extremities. The areas of hypopigmentation have a whorled or streaked configuration and resemble the patterns seen in marble cake. This neurocutaneous syndrome frequently includes neurologic, ocular, and musculoskeletal abnormalities.1 Since Ito first described this variant of systemic depigmented nevus in 1951, more than 70 cases have been reported, many including ocular findings ranging from strabismus to abnormal fundus pigmentation.2,3 We present the case of a 10-year-old girl with incontinentia pigmenti achromians, a prominent retinal pigmentary disorder, and other ocular anomalies.
This female patient had been born with multiple anomalies, including imperforate anus, cleft palate, scoliosis, genu valgum, and a leg length difference that had been treated by resection of the femoral epiphysis. No blisters or cutaneous abnormalities had been recorded at birth.
There is no history of consanguinity, and she has two healthy siblings, a brother 18 years old and a sister 21 years old. There is no history of a skin pigmentation disorder in the family. Her mother has had two miscarriages. In 1988, at age 11 years, the patient was 53 3/4 inches tall (10th percentile), weighed 80 3/4 pounds (40th percentile), and had a head circumference of 53 3/4 cm (60th percentile). She had large streaks of hypopigmentation on her limbs (Fig IA) and whorls of hypopigmentation on her trunk. Her face was elongated and thin, with the right side being larger than the left. Her palate was high and arched, and she had dental malocclusion. Scoliosis of the spine was evident. Her extremities showed clinodactyly of the second and fourth fingers on the right hand and of the second finger on the left hand, as well as mild hyperextensibility of the joints of the hands. Her toes were shortened and overlapping, and there was syndactyly of toes two and three on the left foot (Fig IB).
High-resolution karyotyping showed no abnormalities. Fifty cells were also studied to detect chimerism, but no evidence of mosaicism was found.4 The consulting dermatologist found the skin changes to be typical of incontinentia pigmenti achromians. The consulting otolaryngologist found a bilateral hearing defect diagnosed as otosclerosis. The patient has worn glasses since 3 years of age.
She was first seen in the Department of Ophthalmology in March, 1987. Her corrected vision was RE 20/70 and LE 20/400, with - 8.25 + .75 X 175 RE and - 7.50 sphere LE. She had a left exotropia measuring 65.00 diopters at near by the Krimsky test; there was a mild underaction of each medial rectus and a moderate overaction of the left superior oblique muscle. Lid fissure widths were 8 mm RE and 7 mm LE. The conjunctivae were normal. The corneas measured 11 mm RE and 10 mm LE horizontally; there was a small pannus inferiorly in each eye (Fig 2). The anterior chambers showed no cells or flare. The irides appeared mildly atrophic with irregular pupillary margins. A cortical cataract was present in the right eye, and a clear lens in the left. There was no afferent pupillary defect. Applanation pressures were 16 mm Hg in each eye. The dilated fundus examination showed a small optic disc with an anomalous vascular pattern, a poor macular reflex, and a prominent loss of the retinal pigment epithelium in the posterior aspect of the fundus in each eye (Fig 3).
FIGURE 1: Photographs of the patient's hands and feet show (A) linear hypopigmentation along inner aspect of the right leg (arrows); and (B) the hyperextensibility of the finger joint and syndactyly of the toes.
FIGURE 2: (A) Left eye. External photograph demonstrating the pannus (small arrows). (B) Right eye. External photograph showing the cortical cataract (large arrow) and the small pannus along the nasal limbus (small arrows).
The patient had a rhegmatogenous retinal detachment repair (LE) in 1989, with a resulting visual acuity of 20/400. She also had an extracapsular cataract extraction with posterior chamber intraocular lens RE in 1989, with the best corrected acuity postoperatively being 20/50.
Magnetic resonance imaging of the head, done in 1989, revealed left cranial hemiatrophy with right lateral ventriculomegaly. Cystic changes were seen in the periventricular areas bilaterally. There was a diffuse white matter abnormality with low signal on both Tl and T2 weighted images without evidence of neural migrational defects or gray matter heterotropias. There was a small area of high signal on the Tl image in the thalamus (Fig 4).
An electroretinogram, done late in 1989 under standard conditions, showed low normal amplitudes RE with normal implicit times. The left eye, having undergone previous retinal detachment repair, showed abnormally low amplitudes and normal implicit times (Fig 5). Scotopic blue flash showed RE B- wave amplitude of 214 UV at 48 msec and LE B-wave amplitude of 104 UV at 50 msec. Scotopic red flash showed no recordable cone response. The oscillatory potentials and the photopic flicker were present bilaterally. The photopic response in the right eye was A- wave amplitude -38 UV at 14 msec, and B-wave amplitude 109 UV at 32 msec. The ?-wave in the left eye was - 25 UV at 15 msec, and the B-wave amplitude was 74 UV at 32 msec.
FIGURE 3: (A) Right eye. (B) Left eye. Fundus photographs showing the large geographic areas of hypopigmentation in each eye.
In 1983, Takematsu et al3 combined three of their own cases of incontinentia pigmenti achromians with a review of 70 cases previously reported in the dermatologie literature. Seventy-four percent of these 73 patients demonstrated extracutaneous defects, the most common being central nervous system abnormalities. Frequent central nervous system findings included motor retardation, seizure disorders, and electroencephalographic abnormalities. Two of the patients had a hearing deficit, as did our patient. Musculoskeletal anomalies included cleft lip or palate, scoliosis, genu valgum, clinodactyly, asymmetry of the head, and limb length discrepancy, as were seen in our patient. Other frequent musculoskeletal findings were hypertelorism, malformed auricles, small stature, and macrocephaly.3
FIGURE 4: Magnetic resonance imaging scans of the head demonstrate (A) left cranial hemiatrophy and right ventricular enlargement (small arrows point to bilateral periventricular cystic changes); and (B) high signal area of the right thalamus (large arrow).
The more common form of incontinentia pigmenti (BlochSulzberger syndrome) should be differentiated from incontinentia achromians.5 The Bloch-Sulzberger form is an unrelated disorder - an x-linked genodermatosis characterized by whorled or streaked patterns of hyperpigmentation in the adult. The cutaneous involvement characteristically follows three stages, starting at birth to 6 weeks of age with vesicles and bullae, progressing to the verrucous and plaque stage, then to the pigmented stage. The primary ocular deficiencies of incontinentia pigmenti are the vascular abnormalities of the retina that may lead to a retinal detachment.6 Our patient's family history and constellation of findings would exclude a diagnosis of incontinentia pigmenti, even though central nervous system, ocular, and skeletal abnormalities have been reported in that disorder. We can only presume that our patient's problem represents a sporadic occurrence of an autosomal recessive disorder.
Ocular anomalies associated with incontinentia pigmenti achromians reported in the neurologic and dermatologie literature include strabismus, epicanthal folds, microphthalmia, heterochromia iridis, dacryostenosis, corneal opacities, optic atrophy, ptosis, nystagmus, myopia, and pigmentary disturbances of the fundus.2 The sole description of the ocular characteristics of the syndrome in the ophthalmological literature is that of Reese and Judisch,7 who presented a patient with radial hypopigmented streaks in the fundus.
Our patient's magnetic resonance imaging scan correlates with the computed tomographic findings discussed by Rosemberg et al,2 including the asymmetric ventriculomegaly and diffuse white matter disturbances. The unusual thalamic signals may represent the magnetic resonance imaging correlate of the basal ganglia abnormalities described in an autopsy specimen by Ross et al.8 This patient also has some of the previously reported ocular anomalies seen with incontinentia pigmenti achromians: exotropia, myopia, abnormal optic nerve, and pigmentary changes in the fundus. The corneal asymmetry, pannus, and iris abnormalities found in our patient also may have been noted in other patients, but have not been described clearly enough to be recognized as part of the syndrome. She also developed a cataract in the right eye and had a retinal detachment in the left, amblyopic eye. The electroretinogram of her right eye was normal despite the marked hypopigmentation of the posterior fundus.
FIGURE 5: Electroretinogram demonstrates the low normal amplitude in the right eye of 439 UV in the dark adapted state and the normal implicit time of 52 msec to a bright white light. In the left eye, the amplitude OS was 220 UV and the implicit time was 54 msec.
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