Oculocerebrocutaneous syndrome is a rare congenital disease in which the eyes, skin and brain are involved in the pathological process. Lesions from the organ of vision are represented by orbital cyst syndrome, epibulbar dermoid, micro- or anophthalmos. The most common symptoms of the disease are visual dysfunction, increased lacrimation, impaired binocular vision and spatial perception, delayed psychomotor development. For the diagnosis of pathology, visiometry, biomicroscopy, ultrasound, CT of the head, EEG are performed. In the absence of contraindications from the central nervous system, surgical correction of defects is indicated.
Oculocerebrocutaneous syndrome (Delleman syndrome) was first described in 1981 in two siblings. The genetic link between the development of the disease in close relatives is rarely traced. Pathology occurs with a frequency of 1:500,000 newborns. In 78% of cases it is possible to diagnose orbital cysts, in 97% – lipodermoids. Congenital malformations in patients occur more often on the left side (2:1). According to statistics, about 81% of patients suffer from intellectual retardation. 84% of children have anethoderma, 69% have spot skin defects. The prevalence ratio of the syndrome among men and women is 2:1.
In most cases, Delleman syndrome develops sporadically. Less often there is a genetic predisposition to the occurrence of pathology. There is an autosomal dominant type of inheritance. Etiological factors of the disease are presented:
- Amniotic constriction syndrome. Amniotic cords lead to multiple birth defects, because at the stage of embryogenesis, individual parts of the fetus are squeezed, preventing its development.
- Intrauterine infection of the fetus. Rubella and herpes zoster viruses are endowed with the ability to penetrate the hematophthalmic and blood-brain barrier. Infection with toxoplasmosis in a vertical way can potentiate damage to the organ of vision, brain, and skin.
- Teratogenic factors. Scientists have established a relationship between the development of pathology and teratogenic effects during pregnancy caused by taking medications, the use of alcoholic beverages and narcotic drugs.
- Physical impact. Ionizing and X-ray radiation act as a trigger factor that potentiates the occurrence of oculocerebrocutaneous syndrome.
Somatic mosaicism plays a leading role in the mechanism of development of oculocerebrocutaneous syndrome. Scientists believe that the low prevalence of inherited forms (1:9) is due to the poorly expressed penetrance and expressiveness of the gene. There is a high probability of “de novo” mutation. The occurrence of microphthalmos and the formation of embryonic cysts is due to incomplete closure of the germinal fissure at 5-6 weeks of embryogenesis. Cystic formations are formed from neuroretinal tissue with their further exit through defects in the bone walls into the cavity of the eye socket.
The development of anophthalmos is associated with the influence of teratogenic factors from the 2nd week of intrauterine development. At the same time, the process of laying the eye bubble is disrupted. It is possible to visualize a low-differentiated rudiment of the eye under the influence of pathogens at the time of the already formed eye glass. Local hypo- or aplasia of the skin is caused by a violation of the proliferation of collagen and elastic fibers, as well as stratification of the epidermal layer. Agenesis of the corpus callosum is a consequence of the pathology of the formation of commissural fibers. Hydrocephalus, cortical dysplasia and cerebellar hypoplasia develop when the formation of the anterior cerebral bladder is impaired.
Eye damage is often unilateral, in rare cases there is a bilateral variant of oculocerebrocutaneous syndrome. The disease is characterized by irreversible loss of visual functions, less often – a marked decrease in visual acuity. If only one eye is affected, the ability to stereoscopic vision is impaired. The boundaries of the visual fields are significantly narrowed. Spatial perception is sharply disrupted. Children complain of rapid fatigue when performing visual work (reading, watching TV), which is manifested by increased tearfulness, the appearance of a “veil” or “fog” in front of their eyes.
An increase in the orbital cyst in diameter leads to the appearance of a foreign body sensation, discomfort in the eye socket, less often – pain syndrome. Pronounced exophthalmos is visually determined. Compression of intraocular structures further aggravates the manifestations of visual dysfunction. Neurological symptoms are represented by seizures, disorientation in space, increased anxiety. Parents note that after reaching the age of 6 months, the child’s neuropsychiatric and motor development delay progresses. On the part of the skin, lesions are represented by lipomatosis, focal alopecia, isolated areas of hypoplasia or aplasia of the skin.
Delleman’s syndrome is often complicated by coloboma of the iris. The growth of cystic formations in the cavity of the eye socket leads to compression of the surrounding structures, which entails complete atrophy or subatrophy of the optic disc. The defeat of the uveal tract causes hemorrhages in the vitreous cavity, less often – the anterior chamber. Due to impaired skin development, inflammatory and infectious complications in the form of dermatitis, the formation of multiple areas of ulceration, focal hyperpigmentation are associated in most patients. Patients are at risk of early paralysis and paresis.
The diagnosis is made by the joint efforts of an ophthalmologist, neurologist, dermatologist, geneticist. Diagnosis is based on the identification of a triad of symptoms, including damage to the eyes, brain and skin. In severe forms, oculocerebrocutaneous syndrome can be diagnosed immediately after the birth of a child. Instrumental research methods include:
- Visometry. Depending on the degree of damage to the eyes and brain, the degree of visual dysfunction varies from a slight decrease in visual acuity to complete blindness.
- Biomicroscopy of the eye. The palpebral and orbital conjunctiva are not changed. The conjunctival arches are disproportionate, the orbital slit on the side of the lesion is narrowed. The eyelids are arranged asymmetrically.
- Ultrasound of the eyes. Ultrasound examination is used to study the degree of differentiation of the visual organ, the condition of the posterior segment of the eye with opacity of optical media. With anophthalmos, the eyeball is not detected in the orbital cavity or its low-differentiated rudiment can be detected.
- CT of the head. It allows to diagnose lesions of the nervous system, including such congenital malformations as aplasia of the corpus callosum, hypoplasia of the cerebellum, dropsy of the brain, dysplasia of the cortex.
- Electroencephalography (EEG). It is carried out to determine the functional activity of cortical centers. It makes it possible to assess the degree of violation of brain functions in organic damage to the central nervous system.
- Pathohistological examination. The material for the study is biopsies of the membranes of the eyeball. In patients with microphthalmos, conjunctival lipofibromatosis is detected.
Differential diagnosis is carried out with encephalocraniocutaneous lipomatosis, Goldenhar syndrome, Goltz. With encephalocraniocutaneous lipomatosis, orbital cysts and dysgyria do not develop. The phenotypic differences of Goldman’s disease are represented by epibulbar dermoid, damage to the preauricular zone and spinal defects in the absence of central nervous system abnormalities. In Goltz syndrome, in addition to the eyes, skin and central nervous system, the lower extremities are affected. The disease is diagnosed only in girls, because boys die in utero.
The management tactics of patients with oculocerebrocutaneous syndrome depends on the severity of the pathology. Congenital anomalies of the nervous system are not treatable. In order to reduce intracranial pressure in hydrocephalus, external ventricular drainage or bypass surgery is used. With minor hypoplasia of the eyeball, a posterior sclera bandage is performed. Pronounced microphthalmos or anophthalmos is an indication for stepwise ocular prosthetics. Implantation of a thin-walled prosthesis is performed after enucleation of the eye or removal of its rudiment. Surgical treatment of an orbital cyst is carried out only if there are no contraindications from the central nervous system. Sclerosing drugs are used when it is impossible to perform the operation.
Prognosis and prevention
The outcome of the disease largely depends on the severity of lesions on the part of the nervous system. With a severe course of the disease, children die before reaching the age of ten. Specific preventive measures have not been developed. Women during pregnancy should avoid exposure to teratogenic factors (ionizing and ultraviolet radiation, alcohol consumption, narcotic drugs, medication, X-ray examination). Perinatal screening is difficult because it allows to diagnose pathology only in 20% of cases.