What is the History of Coffin-Lowry Syndrome
Dr. Grange Coffin
Coffin-Lowry syndrome was first identified as a distinct syndrome in 1966, when Dr. Grange Coffin (1923-2022), an American Pediatrician, and colleagues noted two unrelated male patients with an X-linked disease marked by severe mental retardation (MR), short stature, skeletal deformities, and large, soft hands with tapering fingers [1].
The examination of both boys showed developmental retardation, short stature, plump, soft hands with lax, extensible joints and tapered fingers, and a distinctive facial appearance, with wide-set, down-slanted palpebral fissures, epicanthi, ptosis of the upper eyelids, flat maxillae, thick nasal septa, anteverted nostrils, and prominent forehead, brows, ears, and lips. Teeth were few and misaligned. Muscles were weak and hypotonic. The skin was easily stretched. Ligaments were loose, and feet were flat. The gait was slow, awkward, and shuffling. Each boy had kyphosis, a short bifid sternum, and pectus carinatum or excavatum. Both boys fell frequently. One boy had a heart murmur. X-ray studies showed a thick calvarium, small paranasal sinuses, delayed bone age, narrow-necked or “drumstick” terminal phalanges of the fingers, and a frayed and beaked anterior contour of several vertebral bodies. Respiratory infections were frequent. Intelligence quotients (IQ) varied from 54 to 20, and, like other aspects of the syndrome, seemed to grow worse with age. The mothers of both boys, and the sister and half-sister of one of them, had similar but less distinct anomalies and less disability.
Dr. Robert Brian Lowry
Years later and unaware of Coffin’s findings, Dr. Robert Brian Lowry (b. 1932), a British geneticist, made similar clinical observations of a large family containing ten affected members. In 1972, Peter G. Procopis and B. Turner published a case study on a family of four brothers with Coffin-Lowry Syndrome, with female relatives, specifically sisters, only possessing some mild deformities and abnormalities.
In 1975, Dr. Samia Temtamy recognized similarities between these doctors’ work and his own observations of eight comparable cases across three different families displaying symptoms of Coffin-Lowry Syndrome, suggesting that the disorder is more common than believed and often goes underdiagnosed. Temtamy established Coffin-Lowry Syndrome as a novel medical diagnosis and named it for the two doctors who originally described its clinical symptoms. [2]
In 1996, CLS was determined to be caused by a mutation in the RPS6KA3 gene located in the chromosome Xp22.2 and encoding RSK2, a growth-factor regulated protein kinase. [3]
In 2002, Helen Fryssira and RJ Simensen identified a 3 base pair deletion in the gene encoding RSK2, which was the first report of the gene responsible for Coffin-Lowry.
References
[1] – Coffin, G. S., Siris, E., & Wegienka, L. C. (1966). Mental retardation with osteocartilaginous anomalies. American Journal of Diseases of Children, 112, 205–213.
[2] – Temtamy, S. A., Miller, J. D., & Hussels-Maumenee, I. (1975). The Coffin-Lowry syndrome: An inherited facio-digital mental retardation syndrome. Journal of Pediatrics, 86, 724–731.
[3] – https://www.nature.com/articles/5200738.pdf