|Year : 2018 | Volume
| Issue : 3 | Page : 251-254
A boy with bird-like facies and ataxia: Cockayne syndrome
Vishalakshi S Pandit
Department of Dermatology, Venereology and Leprosy, Koppal Institute of Medical Sciences, Koppal, Karnataka, India
|Date of Web Publication||28-Jun-2018|
Dr. Vishalakshi S Pandit
Department of Dermatology, Venereology and Leprosy, Koppal Institute of Medical Sciences, Gangavati Road, Koppal - 583 231, Karnataka
Source of Support: None, Conflict of Interest: None
Introduction: Congenital photosensitive disorders are a group disorders presenting with photosensitivity, short stature (SS), systemic manifestations and susceptibility to malignancy. These include Bloom syndrome, Cockayne syndrome (CS), Rothmund-Thompson syndrome, etc. Early identification and differentiating the syndrome from other congenital disorder is essential as the prognosis of each disorder differs. Case Report: A 4year-old-boy presented with photosensitive rash over the butterfly area of the face. He had history of delayed developmental milestones. His height and weight for his age were below the first percentile. On examination, patient had microcephaly, bird-like facies including sunken eyes, pinched nose, cachectic physique, ataxia and flexural contractures at elbow, knee and ankle joints. Ophthalmic examination showed pigmentary retinopathy on fundoscopy. CT scan of brain revealed bilateral basal ganglia calcification and evidence of premature mild cerebral atrophic changes. On the basis of clinical and lab investigations, we diagnosed this case as CS. Discussion: CS is a rare AR disorder characterized by normal prenatal growth with the onset of growth and developmental abnormalities in the first two years. They have SS, sexual immaturity, and/or retinal pigmentation. Diagnosis of the CS is made by characteristic clinical features specific to this, but the definitive diagnosis is achieved by laboratory investigations such as cytogenetic, biochemical and molecular methods. Although there is no specific treatment, avoidance of sun exposure and protection by sunscreens can help prevent some of the cutaneous eruptions associated with photosensitivity.
Keywords: Ataxia, cerebral atrophy, photosensitivity
|How to cite this article:|
Pandit VS. A boy with bird-like facies and ataxia: Cockayne syndrome. Indian J Paediatr Dermatol 2018;19:251-4
| Introduction|| |
Congenital photosensitive syndromes are a group disorders presenting with photosensitivity, short stature, systemic manifestations, and susceptibility to malignancy. These include Bloom syndrome, Cockayne syndrome (CS), Rothmund-Thomson syndrome More Details, Trichothiodystrophy, xeroderma pigmentosum (XP), etc., CS is a DNA repair-deficient disorder, characterized by various clinical manifestations such as postnatal growth failure, developmental delay, cachexia, cutaneous, auditory, and ocular abnormalities. Early diagnosis and symptomatic treatment of neurological, ocular, and dermatological abnormalities should contribute to prolonging life and elevating quality of life in such patients.
| Case Report|| |
A 4-year-old-boy presented with photosensitive rash over the butterfly area of the face. He had a history of delayed developmental milestones. His height and weight were below the first percentile for his age. On examination, the patient had photosensitive rash on face [Figure 1], bird-like facies including sunken eyes, pinched nose, microcephaly, cachectic physique, senile look, ataxia, and flexural contractures at elbow, knee, and ankle joints. The child had stooped standing posture [Figure 2] and abnormal gait with toe walking. Fundoscopy showed a salt and pepper appearance of retina suggestive of pigmentary retinopathy. His bone age corresponded with the chronological age. Cranial computed tomography scan revealed bilateral basal ganglia calcification and evidence of premature mild cerebral atrophic changes [Figure 3]. On the basis of clinical and laboratory investigations, we diagnosed this case as CS.
|Figure 1: Clinical photo showing photosensitive rash over butterfly area of face|
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|Figure 3: Cranial computed tomography showing bilateral basal ganglia calcification with cerebral atrophy|
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| Discussion|| |
CS is an arthrogryposis-renal multisystem disorder, which was first described in 1936 by Cockayne. The incidence in Western Europe has been recently evaluated as 2.7/million. Over 200 cases have been reported in Europe and the United States, whereas there have been about 70 cases reported in Japan. It is mainly characterized by neurologic and sensory impairment, premature aging, cachectic dwarfism, and photosensitivity. Other features include skeletal abnormalities, progressive neurologic degeneration presenting as delayed psychomotor development, gait defects, mental retardation, endocrinopathies, ear, and ocular abnormalities.
CS can be caused by mutation in two genes, CKN1/CSA and ERCC6/CSB. CSA (25%) and CSB (75%) protein play a key role in transcription-coupled DNA repair, which removes UV-induced DNA lesions only in the actively transcribed DNA strand. Mutations in CSA and CSB lead to a lack of recovery of RNA synthesis in cultured skin fibroblasts after ultraviolet irradiation, a key feature used as the major cellular diagnostic test for CS. This defective repair of ultraviolet-induced lesions may well-explain the cutaneous photosensitivity of patients, but the pathophysiologic mechanisms behind the remaining clinical features are poorly understood.
CS encompasses a wide spectrum of clinical severity, which has been divided into overlapping clinical subgroups of decreasing severity:
CS type I – The classic form with growth and developmental abnormalities beginning in the initial 2 years of life. There is progressive impairment of vision, hearing, and central and peripheral nervous system function, leading to severe disability. Death generally occurs in the first or second decade.
CS type II – Also known as the cerebro-oculo-facial skeletal syndrome (COFS) or connatal CS. This is a severe form, with growth failure present at birth and little or no postnatal neurological development. Ocular and spinal anomalies may be present, and affected children typically die by around 7 years of age.
CS type III – A rare, comparatively mild form characterized by a relatively later onset; there may be essentially normal growth, and cognitive development. XP-CS: an overlap syndrome having features of both.
The clinical diagnosis of classical CS requires the presence of growth failure, neurological dysfunction, and at least three of the following: photosensitivity, pigmentary retinopathy, sensorineural hearing loss, dental caries, and cachectic dwarfism.
Symptoms of photosensitivity start to occur around 6 months after birth. Diverse features can be noted, such as microcephaly, a distinct facies (an aged look, sunken eyes, beak-like nose, and big ears, protruding upper jaw) and other somatic manifestations. These findings are not at all apparent immediately after birth, but start to appear around the age of 2 years and progress with aging.
Musculoskeletal abnormalities present as weakness and joint contractures as early as in neonates and progressive with age. The lower limbs are more often affected than the upper limbs. Patients develop various skeletal deformities in the form of the bird-like face, dental caries, and kyphosis, scoliosis, and osteoporosis in older children and gait defects.
Cardiorespiratory manifestations include dilated cardiomyopathy, hypertension, atherosclerosis, dilated aorta, restricted lung disease, asthma, and recurrent respiratory infections. Cold extremities, representing poor peripheral circulation, are the most common noncardinal feature of CS. This may be a developmental abnormality of CS fibroblasts which have poor vasculature. Hepatic dysfunction as hepatomegaly, cholestasis, and liver cell failure has been seen in many patients, but the underlying reason is not known.
Ophthalmic abnormalities include the development of cataract, retinal degeneration (”salt and pepper retinopathy”) and optic atrophy, all three of which contribute to the visual loss. Other ocular features are photophobia, miotic pupils, nystagmus, corneal ulceration, and scarring.
Common oral and dental findings are delayed deciduous teeth eruption, congenital absence of some permanent teeth (oligodontia), partial macrodontia principally of the central incisors, malocclusion, high-arched palate, and atrophy of the alveolar processes, mandibular prognathism and condylar hypoplasia. Index patient had no abnormality in the oral cavity. Mixed breathing (mouth and nose) leading to dry mouth, immature deglutition, and parafunction such as bruxism, gastro-oesophageal reflux, and vomiting are the functional defects noted in CS patients.
Hearing loss is exclusively bilateral in CS; it may be conductive or sensorineural or mixed type. Pathologic evidence for hearing defects are a loss of inner and outer hair cells and loss of spiral ganglion neurons, degeneration of cochlea, atrophic vestibular maculae and cristae. The latter two also contribute to ataxia and gait abnormalities.
The prevalence of diabetes mellitus and hypothalamic hypogonadism is increased in CS. Most individuals with CS milder form develop secondary sexual characteristics and have a normal reproductive life. Few of the patients are reported to have hypothyroidism.
CS is characterized by both failures of brain development and loss of brain volume attributable in part to progressive leukoencephalopathy. It presents as dementia, spasticity, gait and psychomotor abnormalities. Seizure disorders, choreoathetosis, and tremor have been infrequently reported previously., Neuroimaging feature includes cerebral and cerebellar atrophy, calcifications, and white matter anomalies which are cardinal for the diagnosis of CS. Supratentorial white matter loss and ventricular dilation are probably the earliest detectable signs on brain imaging. There is no clear correlation between the presence of calcifications and specific neurologic symptoms.
CS is easily differentiated from XP by the absence of freckling, skin hyperpigmentation, increased susceptibility to skin cancer and diminished deep tendon reflexes. Though COFS and CS have overlapping clinical features; the absence of microphthalmia, microcornea, cleft palate, and hypertrichosis aids in diagnosing CS. Diagnosis of the CS is made by characteristic clinical features specific to this, but the definitive diagnosis is achieved by laboratory investigations such as cytogenetic, biochemical, and molecular methods. However, these tests are still not widely available and are expensive.
CS patients are apparently not predisposed to skin cancers. The mean age of death is 12.5 years, and the main causes of death are pneumonia and respiratory infections, which could be due to the generally poor condition of the patient.
There is currently no cure for CS. Treatment is generally supportive and includes photo-protection and optimizing nutrition. Strict and complete lifetime protection from UV radiation is advised for prevention of complications. Intake of a diet rich in Vitamin C, Vitamin E, and catechin (which have an antioxidant effect) stimulation of the brain, and encouragement of movement from early childhood may prevent neurological symptoms from advancing.
Dental health education for parents and children should be emphasized and include oral hygiene, assisted brushing techniques, the appropriate use of topical fluoride. The stressful condition may precipitate attacks of hepatic dysfunction and liver support with careful follow-up is extremely essential during the attacks, together with avoidance of hepatotoxic drugs. Genetic counseling should be provided to the parents, as there is 25% recurrence risk for future pregnancies.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understand that their name and initial will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]