The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy.

Hereditary inclusion body myopathy (HIBM; OMIM 600737) is a unique group of neuromuscular disorders characterized by adult onset, slowly progressive distal and proximal weakness and a typical muscle pathology including rimmed vacuoles and filamentous inclusions. The autosomal recessive form described in Jews of Persian descent is the HIBM prototype. This myopathy affects mainly leg muscles, but with an unusual distribution that spares the quadriceps. This particular pattern of weakness distribution, termed quadriceps-sparing myopathy (QSM), was later found in Jews originating from other Middle Eastern countries as well as in non-Jews. We previously localized the gene causing HIBM in Middle Eastern Jews on chromosome 9p12-13 (ref. 5) within a genomic interval of about 700 kb (ref. 6). Haplotype analysis around the HIBM gene region of 104 affected people from 47 Middle Eastern families indicates one unique ancestral founder chromosome in this community. By contrast, single non-Jewish families from India, Georgia (USA) and the Bahamas, with QSM and linkage to the same 9p12-13 region, show three distinct haplotypes. After excluding other potential candidate genes, we eventually identified mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) gene in the HIBM families: all patients from Middle Eastern descent shared a single homozygous missense mutation, whereas distinct compound heterozygotes were identified in affected individuals of families of other ethnic origins. Our findings indicate that GNE is the gene responsible for recessive HIBM.

Hypoglossal nerve paralysis in a burn patient following mechanical ventilation.

Traumatic injury resulting in isolated dysfunction of the hypoglossal nerve is relatively rare and described in few case reports. We present a patient with isolated unilateral palsy of the twelfth cranial nerve (CN XII) resulting from recurrent airway intervention following extensive burn injuries. The differential diagnosis for paralysis of the CN XII is also discussed herein. This case illustrates the significance of comprehensive diagnostic evaluation and the need for refined airway manipulation in patients that require multiple endotracheal intubations.

Une blessure traumatique résultant en un dysfonctionnement isolé du nerf hypoglosse est relativement rare et décrit dans quelques rapports de cas. Nous présentons un patient atteint de paralysie hypoglossal unilatérale isolée à la suite de l'intervention des voies respiratoires récurrentes après de brûlures extensives. Le diagnostic différentiel de la paralysie du nerf crânien (NC XII) est également discuté ici. Ce cas illustre l'importance de l'évaluation diagnostique complète et la nécessité pour la manipulation délicate des voies respiratoires chez les patients qui nécessitent de multiples intubations trachéales.

AlloDerm Sling for Correction of Synmastia After Immediate, Tissue Expander, Breast Reconstruction in Thin Women.

INTRODUCTION: Synmastia is a condition in which the breasts are conjoint and the natural intermammary sulcus is obliterated. It is the rarest type of breast implant malpositioning during breast augmentation; however, it is the most difficult one to correct. AlloDerm is an acellular dermal matrix that is assuming a major role in immediate breast reconstruction in recent years. METHODS: In the past 2 years, we have treated 3 thin women, a total of 6 breasts, for correction of synmastia after bilateral immediate breast reconstruction, using tissue expanders and skin sparing mastectomy. All of them suffered from synmastia, which manifested immediately after the mastectomy and accelerated during tissue expander inflation. We exchanged the expander into silicone implants, and during the same procedure we corrected the synmastia, using an AlloDerm sling. A thick sheet of AlloDerm (Life-Cell Corp, Branchbung, NJ) is used and the AlloDerm sheet is designed into a long narrow sling. Then, the sling is sutured into place. RESULTS: This technique successfully resolved the synmastia. CONCLUSION: The use of an AlloDerm sling to reinforce the capsule and the AlloDerm incorporation into it ensures a sound solution with a low recurrence rate.

Hereditary inclusion body myopathy: the Middle Eastern genetic cluster.

BACKGROUND: Recessively inherited hereditary inclusion body myopathy (HIBM) with quadriceps sparing was initially described only in Jews originating from the region of Persia. The recent identification of the gene responsible for this myopathy and the common "Persian Jewish mutation" (M712T) enabled the re-evaluation of atypical phenotypes and the epidemiology of HIBM in various communities in the Middle East. OBJECTIVE: To test for the M712T mutation in the DNA from HIBM patients in the Middle East. METHODS: DNA from all suspected HIBM patients was tested for the M712T mutation. Unaffected members of families with genetically proven HIBM were studied too. In the majority of families, haplotype construction with markers spanning the 700-kb region of the HIBM gene was performed. RESULTS: One hundred twenty-nine HIBM patients of 55 families (Middle Eastern Jews, Karaites, and Arab Muslims of Palestinian and Bedouin origin) were homozygous for the M712T mutation, and all carried the same haplotype. Five clinically unaffected subjects were also homozygous for the common mutation and haplotype, including two older adults (ages 50 and 68 years). Atypical features with this same mutation were marked quadriceps weakness in five patients, proximal weakness only in two patients, facial weakness in three patients, and a muscle biopsy showing perivascular inflammation in one patient. CONCLUSIONS: The phenotypic spectrum of recessive HIBM is wider than previously described, and the diagnostic criteria for this myopathy must be changed. The Middle Eastern cluster is the result of a founder mutation, with incomplete penetrance, that is approximately 1,300 years old and is not limited to Jews.