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At a glance

Rapidly progressive neurological disorder leading to brain atrophy with intracerebral calcifications, cataracts, microcornea, optic atrophy, progressive joint contractures, and growth failure.

Synonyms

Cerebro-Oculo-Facio-Skeletal Syndrome; COFS Syndrome.

History

First described by S. D. J. Pena and W. K. H. Shokeir in 1974.

Incidence

Very rare. The original reports are mainly from the Manitoba aboriginal population in Canada.

Genetic inheritance

Autosomal recessive.

Pathophysiology

Pena-Shokeir Syndrome Type II is caused by mutations in the ERCC6 gene on chromosome 10q11.23. This gene is part of the nucleotide excision repair (NER) pathway, a complex system that eliminates a broad spectrum of structural deoxyribonucleic acid (DNA) lesions. This multistep “cut-and-patch” repair system deals with the broad class of helix-distorting lesions, including UV-induced DNA lesions and numerous bulky chemical adducts and intrastrand cross-links. Defects in this pathway lead to profound photosensitivity.

Clinical aspects

Clinically evocated by association of arthrogryposis, ocular signs, and growth failure. Many features are apparent at birth. The disease involves head and neck (microcephaly, micrognathia/retrognathia, upper lip overlaps the lower lip, sloping forehead, long philtrum and prominent nasal root, large ear pinnae), central nervous system (CNS) (mental retardation, hemiparesis, hypoplasia of the optic tract, focal microgyria, corpus callosum agenesis, seizures, infantile spasm, hypotonia, third ventricle subependymal focal gliosis, cerebellar hypoplasia), eyes (cataracts, blepharophimosis, microphthalmia, deep-set eyes, and nystagmus), skeleton (osteoporosis, vertebral segmentation defects, kyphoscoliosis, coxa valga, shallow acetabular angle, elbow and knee flexion contractures, camptodactyly, vertical talus, rocker-bottom feet, longitudinal groove on the soles, posterior placement of the second metatarsal). Other inconstant features can include widely spaced nipples, insulin resistance, hirsutism, and heart defects. Death, associated with feeding difficulties and pneumonia, usually occurs by the age of 5 years but patients with milder forms may survive beyond childhood.

Precautions before anesthesia

Active respiratory tract infections should be sought and treated. Evaluate tracheal intubation (clinical, radiographs, fiberoptic) because of facial malformations and evaluate neurological function (clinical, EEG, CT/MRI).

Anesthetic considerations

Anesthesia care has not been described in the literature. The features of the disease suggest that tracheal intubation may be difficult. Patient positioning and intravascular access may be difficult because of contractures. Patients are prone to seizures.

Pharmacological implications

Chronic use of anticonvulsants may alter the metabolism of some anesthetic agents.

Other conditions to be considered

  • Neu-Laxova Syndrome: Autosomal recessive condition characterized by multiple abnormalities at birth such as microcephaly and abnormal limbs, skin, external genitals, and placenta.

  • Potter Syndrome: Characterized by an excess of skin dehydrated looking, a flattened face with a “parrot-beak” nose, eyelid anomalies, micrognathism, and low-set ears. A kidney may ...

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