Bi-allelic variants in MYH3 cause recessively-inherited arthrogryposis.

Arthrogryposis is a clinical feature defined by congenital joint contractures in two or more different body areas which occurs in between 1/3000 and 1/5000 live births. Variants in multiple genes have been associated with distal arthrogryposis syndromes. Heterozygous variants in MYH3 have been identified to cause the dominantly-inherited distal arthrogryposis conditions, Freeman-Sheldon syndrome, Sheldon-Hall syndrome, and multiple pterygium syndrome. In contrast, MYH3 variants underlie both dominantly and recessively inherited Contractures, Pterygia, and Spondylocarpotarsal Fusion syndromes (CPSFS) which are characterized by extensive bony abnormalities in addition to congenital contractures. Here we report two affected sibs with distal arthrogryposis born to unaffected, distantly related parents. Sequencing revealed that both sibs were homozygous for two ultra-rare MYH3 variants, c.3445G>A (p.Glu1149Lys) and c.4760T>C (p.Leu1587Pro). Sequencing and deletion/duplication analysis of 169 other arthrogryposis genes yielded no other compelling candidate variants. This is the first report of biallelic variants in MYH3 being implicated in a distal arthrogryposis phenotype without the additional features of CPSFS. Thus, akin to CPSFS, both dominant and recessively inherited distal arthrogryposis can be caused by variants in MYH3.

Validation of the French version of the KOOS-child questionnaire.

PURPOSE: The Knee Injury Osteoarthritis Outcome Score (KOOS) questionnaire is one of the frequently used outcome scores in pediatric studies. However, a recent study demonstrated that the pediatric population had a limited understanding of some of its questions. Therefore, the KOOS-Child questionnaire was developed specifically for this population. Our team produced a French adaptation based on the English version. The objective of the current study was to validate the French adaptation of the KOOS-Child questionnaire. METHODS: After ethic board approval, the questionnaire was translated from English to French by two French speaking orthopedic surgeons. Following consensus, the translated version was retranslated to English by a professional translator. A group of experts compared the original and back translated version and decided on a final adapted questionnaire version. Ninety-nine 8-16 year-old patients were prospectively recruited from our pediatric orthopedic surgery clinic. Twenty-one control participants and 78 patients suffering from knee pain were recruited. The participants were asked to answer the translated French version of the KOOS-Child questionnaire and two validated French pediatric quality of life surveys. RESULTS: Statistical analysis demonstrated no statistically significant demographic difference between the control population and the patients suffering from a knee pathology. The mean for the five different domains of the KOOS-Child questionnaire showed statistical differences (p < 0.001) between the two groups. Construct validity was demonstrated through testing of previously validated hypothesis of correlation. Internal consistency was also confirmed in injured patients. CONCLUSIONS: In conclusion, the current study results demonstrate good to excellent internal consistency, good construct validity and inconclusive discriminant capacity of the French adaptation of the KOOS-Child questionnaire. LEVEL OF EVIDENCE: II.

A de novo frameshift FGFR1 mutation extending the protein in an individual with multiple epiphyseal dysplasia and hypogonadotropic hypogonadism without anosmia.

Multiple epiphyseal dysplasia (MED) is a genetically and clinically heterogeneous disease with both dominant and recessive inheritance. Eight different genes are known to cause the disease but in 15% of cases of MED, no mutation is found. Fibroblast growth factor receptor 1 (FGFR1) is a crucial regulator of bone formation and when mutated, can cause diseases with skeletal manifestations; nevertheless, MED has not been described in individuals with FGFR1 mutations. In this report, we describe a proband with MED and congenital normosmic hypogonadotropic hypogonadism (HH). DNA analysis showed a de novo frameshift variant in FGFR1 likely explaining the HH (p.Arg852Thrfs*165). No other mutation was found after a large gene sequencing panel, exome sequencing and an array CGH, except for a variant of unknown significance in FBN1 (rs755375255), but there were no features of a disease associated with FBN1 mutations and this variant is found a few times in population databases. We thus discuss the possibility that MED might be a new skeletal feature associated with FGFR1 mutations.

Stage I indexing to replace a failed implant in an edentulous arch: a clinical report.

Implant failure may complicate and lengthen a planned treatment. This article describes a modified stage I indexing technique for registering the position of an implant and replacing a failed implant, allowing prosthesis fabrication time and healing time to be coincidental. The clinician can proceed as originally planned with a minimal increase in overall treatment time.