The natural history of spinal deformity in patients with Coffin-Lowry syndrome

Abstract

PurposeLittle is known about the natural history of spinal deformities in Coffin-Lowry syndrome (CLS). Our goal was to evaluate the spinal deformity progression and clinical impact.MethodsIn this institutional review board-approved study, we performed a multinational retrospective review of six male CLS patients, aged 13 to 22 years at final follow-up, for a mean of 7.25 years (3 to 13).ResultsAll showed delayed skeletal maturity. Three had calcifications of their lower cervical ligamentum flavum, all experienced neural axis abnormalities, including lower extremity weakness, numbness and tingling and in one, quadriparesis. Only two were ambulatory at final follow-up.All had significant spinal abnormalities, including severe progressive thoracic lordosis, thoracolumbar kyphosis and scoliosis. All had undergone spinal fusion or were being evaluated for surgery.ConclusionCLS is a rare X-linked mutation in the RSK2 gene, affecting between 1/50 000 to 100 000 people. There are two reports in the literature of patients with calcifications of their ligamentum flavum. Both had neural axis abnormalities and one had acute onset quadriplegia. Analysis of their ligamentum flavum found abundant central calcifications. Despite our small cohort we found 50% had calcifications and 100% had neurologic consequences associated with those calcifications. There was a 100% rate of deformity progression.They all exhibited delay in skeletal maturity, which mandates longer follow-up and has implications for surgical planning.From our cohort and literature review, the natural history of CLS supports frequent patient evaluation and a lower threshold for correction of spinal deformities. Aiming to avoid spinal cord compression and improve or avoid neurological deterioration.Level of EvidenceIV - retrospective study

Growth Concerns in Coffin–Lowry Syndrome: A Case Report and Literature Review

“…What is more, RSK2 out of function is related with bone mineralization abnormal and also induces spine malformations and calcifications of ligamentum flavum, such as thoracic lordosis, scoliosis, kyphosis, and degenerative disc disease (19, 20). Previous reports identified the ERK/ RSK2 as a regulator of bone formation in vivo (7).…”

Severe Restrictive Lung Disease in One of the Oldest Documented Males With Coffin-Lowry Syndrome

“…Welborn et al found in their cohort study that frequent evaluation of skeletal changes should be carried out by health providers with a lower threshold for surgical intervention to limit spinal cord compression. 6 His severe skeletal deformities with resultant anatomical flexion, rotation, and contractures created significant difficulty in visualizing where vertebral bodies begin and end, making it impossible to gauge where to draw the necessary Cobb’s angle lines. Moreover, the severity of his scoliosis led to significant difficulties with ventilation.…”