ABSTRACT
BACKGROUND: A gene for Larsen syndrome was recently described, and mutations were reported in five cases. OBJECTIVE: To test whether mutations in this gene, FLNB, could explain the disease in our independent collection of sporadic and dominant Larsen syndrome cases; and to test whether mutations occurred in a non-random pattern. RESULTS: Missense mutations were found in each of five cases. Four of the five were new; one was reported in a sporadic case in the original Larsen syndrome study of five cases. All mutations from the two studies were compiled. Clustered mutations were observed within three filamin B protein domains: the calponin homology 2 domain, repeat 14, and repeat 15. This suggested that as few as five (of the total of 46) coding exons of FLNB could be screened to detect Larsen syndrome mutations. Four of these exons were screened in a sixth (sporadic) case and a previously reported G1691S substitution mutation detected. CONCLUSIONS: Mutations in FLNB may be responsible for all cases of Larsen syndrome. They appear to occur in specific functional domains of the filamin B protein. This should simplify diagnostic screening of the FLNB gene. Analyses in larger patient series are warranted to quantify this. The study confirmed the extreme variability in clinical presentation and the presence of unaffected carriers. A molecular screen would be valuable for diagnosis and genetic counselling.
Subject(s)
Abnormalities, Multiple/genetics , Contractile Proteins/genetics , Foot Deformities, Congenital/genetics , Joint Instability/genetics , Microfilament Proteins/genetics , Mutation, Missense , Abnormalities, Multiple/diagnosis , Amino Acid Sequence , Contractile Proteins/chemistry , Face/abnormalities , Female , Filamins , Foot Deformities, Congenital/diagnosis , Genetic Testing , Humans , Joint Instability/diagnosis , Male , Microfilament Proteins/chemistry , Molecular Sequence Data , Pedigree , Sequence Alignment , SyndromeABSTRACT
Twenty-two patients (34 feet) with severe, flexible, planovalgus feet due to neuromuscular conditions were treated with subtalar staple arthroereisis. Patients were followed up for an average of 5 years (range, 2.5-9 years). Of the 34 feet, 18 did not require revision surgery; however, the remaining 16 feet required revision at an average of 39 months after surgery (range, 9-63 months). Revision procedures consisted of hardware removal in four cases, repeated subtalar stapling in one, triple arthrodesis in two, and calcaneal with or without cuboid and cuneiform osteotomy in nine feet. The long-term results of subtalar staple arthroereisis were unpredictable, and although it was effective in approximately half of our patients, we no longer recommend this procedure for the correction of the neuromuscular planovalgus foot deformity.
Subject(s)
Foot Deformities, Acquired/surgery , Neuromuscular Diseases/complications , Subtalar Joint/surgery , Surgical Stapling , Adolescent , Child , Child, Preschool , Female , Foot Deformities, Acquired/etiology , Humans , Male , Osteotomy , ReoperationABSTRACT
We performed combination calcaneal-cuboid-cuneiform osteotomies in 18 patients (26 feet) with severe valgus foot deformity. The operation consists of a sliding calcaneal osteotomy, an opening-wedge cuboid osteotomy, and a pronation, plantar flexion closing-wedge osteotomy of the medial cuneiform in addition to appropriate soft-tissue releases. The preoperative goals of restoring the axis of the foot parallel to the axis of progression and relieving pain, as well as shoe, brace, and skin problems, were met in 23 of the 24 feet available for review at an average of 18 months after surgery. This procedure has the advantage of localized correction of deformity without the problems associated with arthrodesis.