26 Cockayne Syndrome
CS
Microcephaly, progressive CNS degeneration, thin facies, beaked nose, precociously senile appearance, eye anomalies, photodermatitis, sensitivity to sun- light
Frequency: Rare (over 150 cases published).
Genetics
Autosomal recessive (OMIM 216400, 216411), geneti- cally heterogeneous; there are at least four forms; the CSA gene, a WD repeat protein, maps to chromosome 5; CSB has been identified in the ERCC6 (excision re- pair cross complementing group 6, OMIM 133540) gene mapped to 10q11 and occurs as part of xero- derma pigmentosum (XP) complementing group B;
two other CS forms are part of the XP comple- menting groups D (OMIM 126340), ERCC2 gene, mapped to chromosome 19q13.2-q13.3, and G (OMIM 133530), ERCC5 gene, mappet to chromosome 13q33.
Clinical Features
• Normal early development
• Cachectic dwarfism, disproportionately long limbs, large hands and feet
• Precociously senile appearance, sensitivity to sun- light (‘butterfly’ distribution)
• Microcephaly, thin facies, loss of subcutaneous fat with age, beaked nose, prognathism
• Sunken eyes
• Retinal degeneration, optic atrophy, corneal desic- cation, cataracts, nystagmus
• Large ears, deafness
• Poikiloderma
• Kyphoscoliosis, horse-riding stance
• Hypertension, proteinuria, glomerulosclerosis
• Mental retardation, dementia, cerebellar ataxia, choreoathetosis
• Death from early atherosclerosis Differential Diagnosis
• Cerebro-oculo-facial-skeletal (COFS) syndrome (allelic)
• CAMFAK syndrome
• Progeria
• Werner syndrome
• Xeroderma pigmentosum
• Bloom syndrome
Radiographic Features Skull
• Microcephaly, frontal bossing
• Thickened cranial vault
(frontal and parietal regions) and skull base
• Intracranial calcifications
• Small sella turcica
• Small mandible
• Hypoplastic sinuses and mastoids
• Dental abnormalities Spine
• Ovoid vertebral bodies with anterior notching
• Biconvex flattening of vertebral bodies
• Increased AP diameter of vertebral bodies
• Scalloping and posterior wedging
• Disc space calcification
• Kyphosis (thoracic) Extremities
• Slender long bones
• Disproportionately long limbs
• Bowed fibulae
• Bulky metaphyses and epiphyses
• Coxa valga
Cockayne Syndrome 654
Fig. 26.1. Patient 1, age 1 year and 6 months. Microcephaly, frontal bossing, beaked nose, large low-set ears, deep-set eyes.
(From archive of Dr. P. Balestrazzi, University of Parma, Italy, with permission)
Cockayne Syndrome 655
C
Fig. 26.2. Patient 1, 1 year and 6 months. Hypoplasia of the facial bones, small mandible, mildly thickened calvarium, and frontal bossing. (From archive of Dr. P. Balestrazzi, University of Parma, Italy, with permission)
Fig. 26.3. Patient 2, age 5 years. The vertebral bodies show increased antero-posterior dia- meter, platyspondyly, tongue-like protrusion of their anterior aspects, and posterior scalloping.
Note biconvex end-plates of proximal lumbar vertebrae. (Reprinted, with permission, from Canepa et al. 1996)
Fig. 26.4 a, b. Patient 2, age 5 years.
Note elongated, slender long bones, prominent metaphyses, coarse trabecular epiphyseal pat- tern, and coxa valga. (Reprinted, with permission, from Canepa et al. 1996)
a b
Hands and Feet
• Large hands and feet
• Large tarsal and carpal bones
• Second metacarpal pseudoepiphysis
• Short and broad tubular bones of hands and feet
• Ivory epiphyses
• Cone-shaped epiphyses
• Short 2nd toes Joints
• Joint limitation, or contractures Generalized Bone Defects
• Osteoporosis Chest
• Thin ribs
• Thin clavicles Pelvis
• Small pelvis
• Squared-off iliac wings, hypoplastic acetabula
Bibliography
Canepa G, Maroteaux P, Pietrogrande V. Sindromi dismorfiche e malattie costituzionali dello scheletro. Piccin, Padova, 1996
Henning KA, Li L, Iyer N, McDaniel LD, Reagan MS, Legerski R, Schultz RA, Stefanini M, Lehmann AR, Mayne LV, Friedberg EC. The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a sub- unit of RNA polymerase II TFIIH. Cell 1979; 82: 929–34 Lehmann AR, Bootsma D, Clarkson SG, Cleaver JE, McAlpine
PJ, Tanaka K, Thompson LH, Wood RD. Nomenclature of human DNA repair genes. Mutat Res 1994; 315: 41–2 Macdonald WB, Fitch KD, Lewis IC. Cockayne’s syndrome:
a heredo-familial disorder of growth and development.
Pediatrics 1960; 25: 997–1007
Nance MA, Berry SA. Cockayne syndrome: review of 140 cases.
Am J Med Genet 1992; 42: 68–84
Stefanini M, Fawcett H, Botta E, Nardo T, Lehmann AR: Genet- ic analysis of twenty-two patients with Cockayne syn- drome. Hum Genet 1996; 97: 418–23
Talwar D, Smith SA. CAMFAK syndrome: a demyelinating inherited disease similar to Cockayne syndrome. Am J Med Genet 1989; 34: 194–8
Cockayne Syndrome 656
Fig. 26.5 a, b. Patient 3, age 2 years. Note short, stubby tubular bones in hands compared with slender tubular bones in fore- arms. Also note prominent carpal bones. (Reprinted, with per- mission, from Canepa et al. 1996)
a b
Fig. 26.6. Patient 1, age 1 year and 6 months. There is 5th mid- dle phalanx hypoplasia with clinodactyly, hypoplasia of the distal phalanges of the fingers, and striking osteoporosis.
(From archive of Dr. P. Balestrazzi, University of Parma, Italy, with permission)
