Phenotypic variability of CMT4C in a French-Canadian kindred.

INTRODUCTION: Charcot-Marie-Tooth type 4C (CMT4C) is an autosomal recessive dysmyelinating neuropathy characterized by precocious and rapidly progressive scoliosis. METHODS: Patients in a French-Canadian kindred were evaluated with clinical examination, electrophysiologic study, and genomic DNA extraction. RESULTS: Six of 10 siblings were clinically symptomatic with supportive electrophysiologic features. The proband presented with regional side-to-side sensorimotor asymmetry, typical pes cavus without obvious scoliosis, and unremarkable plain films of the spine. Affected siblings all share symptoms of foot deformity but have variable onset of neuropathic symptoms, degree of extremity weakness, progression of symptoms, and, most notably, evidence of scoliosis. DNA sequence analysis revealed a novel combination of 2 known recessive mutations, p.R904X and p.R954X, in the SH3TC2 gene. CONCLUSIONS: A broad spectrum of phenotypes should be considered in the possible diagnosis of CMT4C. The absence of scoliosis or late-onset symptoms should not exclude SH3TC2 from the list of candidate genes under consideration. Age of onset and clinical features were variable and suggest that polygenic factors contribute to the final phenotype.

The level of evidence presented at plastic surgery meetings: what do we have to learn?

BACKGROUND: Internationally, plastic surgery societies have placed an increasing emphasis on the importance of evidence-based medicine. The authors aimed to categorize levels of evidence of podium presentations at three major North American plastic surgical meetings, and to assess the factors associated with a higher level evidence. METHODS: Presentations at the 2010/2011 meetings of three of the largest societies of plastic surgeons in North America were evaluated for the area of research, number and origin of authors, subdomain of plastic surgery, number of centers of collaboration, number of subjects, study subtype, and level of evidence. RESULTS: One hundred eighty-eight presentations were screened, and 126 met eligibility criteria. The American Society of Plastic Surgeons was the largest meeting with 74 presentations (58.7 percent). Breast (23.8 percent) and craniofacial (21.4 percent) topics were most frequently covered. Most studies had five or fewer authors (76.4 percent), were conducted at a single center (84.3 percent), were therapeutic (89.7 percent), and had 50 or fewer subjects (36.8 percent). Two studies (1.6 percent) were level I, 11 (8.7 percent) were level II, 54 (42.9 percent) were level III, 46 (36.5 percent) were level IV, and 13 (10.3 percent) were level V. Overall, the mean level of evidence was 3.45, and one of every 10 presentations was of higher level of evidence (level I or II). Higher level evidence presentations were found to be associated with multicenter studies. CONCLUSIONS: Evidence presented at major plastic surgical meetings is rarely level I and infrequently level II. Opportunities to create greater awareness of the need for prospective high-level studies are needed.

Primary osteoporosis without features of OI in children and adolescents: clinical and genetic characteristics.

Our aim was to characterize clinical findings and familial associations, and to examine candidate genes for disease-causing mutations in a cohort of children suffering from primary osteoporosis without features of osteogenesis imperfecta. Patients with osteoporosis and their nuclear families were studied. Medical history was reviewed. Calcium homeostasis parameters were measured and spinal radiographs obtained. BMD was determined by DXA for patients, parents and siblings. LRP5, LRP6, and PTHLH genes were sequenced. Twenty-seven patients (14 males) from 24 families were recruited. Median age at presentation was 10.1 years (range 3.3-15.6 years). One-third of the children had at least one parent with a BMD below the expected range for age. LRP5, LRP6, and PTHLH showed no causative mutations. Four polymorphisms in LRP5 were overrepresented in patients; the minor allele frequency of Q89R, V667M, N740N, and A1330V was significantly higher than in controls. Age of onset, clinical severity, and inheritance patterns are variable in children with primary osteoporosis. Several patients had evidence suggestive of familial transmission. The underlying genetic factors remain to be elucidated.