Clinical Features in Cockayne and Related Syndromes | 7

ABSTRACT

Ch apter 1 Clinical Features in Cockayne and Related Syndromes Grace S. Sun* and Denise W. Metry Abstract C ockayne syndrome is an autosomal recessive disorder in which patients develop growth retardation and neurodevelopmental impairment. The clinical symptoms may be present at b irth and typically develop by age two. Patients usually do no t survive to adulthood. In addition to growth and developmental delay, affected children have a typical facies, ophthalmic and auditory disorders and sun-sensitivity. The m utation o f genes CSA or CSB leads to impaired DNA-repair and increased D N A damage to oxidation, radiation and U V exposure. Patients with UV-Sensitive syndrome and X P also have increased sun sensitivity bu t do no t share the increased cellular apoptosis seen in Cockayne syndrome. The gene products o f CSA and CSB have many complex protein interactions involving DNA-repair, cell cycle regulation and chromatin structure. Research continues to report more proteins interacting with CSA and CSB proteins. Historical BackgroundIn 1936, a London physician, Edward Alfred Cockayne, described two siblings w ith a syndrome o f “dwarfism, retinal atrophy and deafness”.1 Since then, more than 180 cases o f Cockayne syndrome (CS) have been reported in the literature. CS, an autosomal recessive disorder, has no apparent gender or ethnic predilection.2 The classic clinical features include profound growth retardation, microcephaly, ophthalmologic abnormalities, neurodevelopmental impairment, photosensitive skin rash and progeroid facies.3 W hile most CS children are o f norm al birth weight (Fig. 1), profound growth retardation and microcephaly become apparent w ithin the first two years o f life. This type o f growth retardation affects the child s weight significantly more than the height and is term ed “cachectic dwarfism”.4 CS Phenotyp esCS has been divided into four clinical phenotypes:CS Type I is also known as the “classic” form. Affected children are o f normal b irth weight, but develop profound growth retardation by age two (Fig. 1). Children are typically below the fifth percentile for height, weight and head circumference and also tend to develop progressive audiologic, visual and neurologic deficits. D eath usually occurs by the first or second decade o f life (Fig. 2).CS Type II is also known as cerebro-oculo-facial syndrome (COFS), Pena-Shokeir syndrome Type II, or “conatal” CS. These children are even more severely affected than those with Type I, presenting at b irth w ith intrauterine growth retardation, followed by poor postnatal growth and rapidly progressive neurologic impairment. Thirty percent have ophthalmologic abnormalities,