PEDBASE.org - The Pediatric Database - Detailed information of COCKAYNE SYNDROME

COCKAYNE SYNDROME

DEFINITION:

A neurodegenerative disorder characterized by degeneration of CNS white matter resulting in neurological, ocular, cutaneous, and musculoskeletal manifestations.

EPIDEMIOLOGY:

incidence: rare (about 60 cases reported)
age of onset:
- first 6 months of life (photosensitive dermatitis)
risk factors:
- familial - autosomal recessive
  - chrom.#: ?
  - gene: ?
- M = F

PATHOGENESIS:

1. Background

etiology unknown
theories range from a leukodystrophy to a deficiency of an enzyme involved in the repair of cellular DNA following damage by UV light or chemical mutagens
normal in the first 6 months of life (except for a photosensi-tive dermatitis) followed by a drastic and progressive decline in physical and mental development (developmental delay begins in the 2nd half of the first year of life) eventually leading to dwarfism and mental retardation

PATHOLOGY:

1. Central and Peripheral Nervous System

segmental demyelination with preserved islands of myelin
findings consistent with a degenerative process
- diffuse proliferation of bizarre astrocytes
- neurofibrillary tangles

TYPES:

Type I - Late-Onset

Type II - Prenatal-Onset

CLINICAL FEATURES:

1. Type I - Late-Onset

1. Neurological Manifestations

cerebellar dysfunction with ataxia and/or tremor
hydrocephalus (normal-pressure) with progressive apraxic gait and urinary incontinence
mental retardation
microcephaly
spasticity with reduced deep tendon reflexes

2. Ophthalmologic Manifestations

corneal opacities
impaired lacrimation
photophobia
poor pupillary response
cataracts
speckled pigmentation of the fundus
retinitis pigmentosa -> retinal atrophy
optic atrophy -> decreased visual acuity -> blindness

3. Cutaneous Manifestations

1. Photosensitive Dermatitis

sensitivity of the skin to sunlight
facial rash
scaly rash, dyspigmentation, scarring, atrophy of exposed areas

4. Musculoskeletal Manifestations

1. Facial Features

wizened senile-like appearance
- due to loss of adipose tissue from the face
- malformed ears, beaked nose, sunken eyes, prog-nathism, pinched facies, spare hair

2. Skeletal Features

growth retardation
decreased subcutaneous fat with short stature (cachectic dwarfism)
progressive kyphosis
flexion contractures of the large joints
relatively long limbs

5. Other Manifestations

hearing impairment -> deafness
dental caries
renal disease

2. Type II - Prenatal-Onset

1. Neurological Manifestations

prenatal growth failure (birth weights between 1,540 and 2,550 g)
congenital microcephaly
mental retardation (severe)

2. Ophthalmologic Manifestations

sunken eyes
cataracts

3. Musculoskeletal Manifestations

flexion contractures of joints
kyphosis
failure to thrive

4. Other Manifestations

aspiration pneumonia due to GE reflux or poor feeding
cryptorchidism
sparse hair
hearing impairment -> deafness

INVESTIGATIONS:

1. Imaging Studies

1. CT/MRI

progressive leukodystrophy
thickening of the calvarium
leptomeningeal thickening
intracranial calcifications - basal ganglia, cerebellum
patchy demyelination
cerebellar atrophy

2. Skeletal X-Rays

steepening of the iliac angle in a small pelvis
slender clavicles and ribs
osteoporosis

2. Nerve Conduction Velocity

slowed

MANAGEMENT:

1. Supportive

no treatment for underlying disease
multidisciplinary approach
- Paediatrics, Neurology, Ophthalmology, Orthopedics
- genetic counselling

2. Surgery

relief of hydrocephalus

3. Prognosis

life expectency
- death in the 1st and 2nd decades (Type I)
- death in the first five years of life (Type II)

Pediatric Database - COCKAYNE SYNDROME

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