27 Coffin-Lowry Syndrome
Coffin-Lowry Syndrome 657
CLS
Mental retardation, square forehead, bitemporal nar- rowing, pugilistic nose, prominent lips, large ears, tapered fingers, kyphoscoliosis
Frequency: Rare (over 100 cases published).
Genetics
X-linked dominant (OMIM 303600) with mild ex- pression in female heterozygotes; mutation in RSK2, a serine-threonine protein kinase involved in cell proliferation and differentiation, mapped to Xp22.2.
Clinical Features
• Mental retardation, hypotonia
• Small stature, stooped posture
• Square forehead, bitemporal narrowing
• Progressive coarsening of facial features
• Full outer eyebrows,hypertelorism,down-slanting palpebral fissures
• Broad,‘pugilistic’ nose, thick nasal septum, anteverted nostrils
• Large mouth, thick lips, pouting lower lip, hypodontia, conical crowded incisors
• Maxillary hypoplasia, long philtrum
• Prognathism
• Large, protruding ears, sensorineural hearing deficit
• Cervical hyperlordosis
• Pectus carinatum/excavatum
• Kyphoscoliosis
• Extremely large, puffy hands,
with hyperextensible, distally tapered fingers
• Flat feet
Differential Diagnosis
• Fragile X syndrome
• Sotos syndrome
• Williams syndrome
• Mucopolysaccharidoses
Radiographic Features Skull
• Thickened calvaria (especially in frontal area)
• Large anterior fontanel, persistently open cranial sutures
Chest
• Short bifid sternum
• Pectus carinatum/excavatum Spine
• Kyphosis, gibbus deformity (thoracic)
• Narrow intervertebral disc spaces
• Anterior vertebral body defects
• Ligamenta flava calcification
C
Fig. 27.1 a, b. Patient 1, age 25 years.
Squared forehead, temporal nar- rowing, coarse facial features, prominent supraorbital ridges and eyebrows, broad nose, large mouth, thick lips, pouting lower lips, large protruding ears, and thoracic gibbus
a b
Extremities
• Pseudoepiphyses of metacarpals
• Hypoplastic, drumstick-shaped terminal phalanges
• Poorly modeled middle phalanges
• Short hallux
• Coxa valga
• Lower limb discrepancy Pelvis
• Narrow iliac wings Generalized Bone Defects
• Delayed bone maturation
Bibliography
Abidi F, Jacquot S, Lassiter C, Trivier E, Hanauer A, Schwartz CE. Novel mutations in Rsk-2, the gene for Coffin-Lowry syndrome (CLS). Eur J Hum Genet 1999; 7: 20–6
Biancalana V, Triver E, Weber C, Weissenbach J, Rowe PSN, O’Riordan JLH, Partington MW, Heyberger S, Oudet C, Hanauer A. Construction of high-resolution linkage map for Xp22.1-p22.2 and refinement of the genetic localization of the Coffin-Lowry syndrome gene. Genomics 1994; 22:
617–25
Gilgenkrantz S, Mujica P, Gruet P, Tridon P, Schweitzer F, Nivelon-Chevallier A, Nivelo JL, Couillault G, David A, Ver- loes A, Lambotte C, Piussan C, Mathieu M. Coffin-Lowry syndrome: a multicenter study. Clin Genet 1981; 34: 230–45 Jacquot S, Merienne K, Trivier E, Zeniou M, Pannetier S, Hanauer A. Coffin-Lowry syndrome: current status. Am J Med Genet 1999; 85: 214–5
Young ID. The Coffin-Lowry syndrome. J Med Genet 1988; 25:
344–8 Coffin-Lowry Syndrome
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