Fibromyalgia in patients with chronic CCD and CMD - A retrospective study of 555 patients.

OBJECTIVE: Craniomandibular dysfunction (CMD) and craniocervical dysfunction (CCD) are clearly defined musculoskeletal pain syndromes. Relationships with fibromyalgia syndrome (FMS) have not yet been investigated. The aim of the present study is to establish possible relationships between FMS and CMD/ CCD. METHODS: In a retrospective study, 555 patients with CCD and CMD were investigated with respect to the diagnostic criteria of FMS. In addition to otolaryngologic and dental examination, an instrumental functional analysis for the diagnosis of CMD/CCD was performed. RESULTS: Three hundred fifty-one (63%) of the 555 patients evaluated met the diagnostic criteria for FMS. Seventy-two percent of the patients had a widespread pain index of at least 7 and a severity scale score of at least 5. Twenty-nine percent had a widespread pain index of 3-6 and a severity scale score of at least 9. Using myocentric bite splint therapy and therapy with oral orthesis in combination with neuromuscular relaxation measures, a good to very good improvement of physical symptoms was seen in 84% of CMD-FMS patients, and an improvement of the symptoms in the jaw was achieved in 77% of cases. DISCUSSION: The substantial proportion of CMD and CCD patients who meet the criteria for FMS emphasizes the complexity of the two diseases. It must be assumed that FMS is a crucial factor for the formation of CMD and CCD. Conversely, CMD/ CCD could also be responsible for diverse clinical pictures of the FMS. FMS patients with synchronous CCD/CMD benefit from an interdisciplinary CMD/CCD treatment.

Functional characterization of two novel splicing mutations in the OCA2 gene associated with oculocutaneous albinism type II.

Oculocutaneous albinism (OCA) is characterized by hypopigmentation of the skin, hair and eye, and by ophthalmologic abnormalities caused by a deficiency in melanin biosynthesis. OCA type II (OCA2) is one of the four commonly-recognized forms of albinism, and is determined by mutation in the OCA2 gene. In the present study, we investigated the molecular basis of OCA2 in two siblings and one unrelated patient. The mutational screening of the OCA2 gene identified two hitherto-unknown putative splicing mutations. The first one (c.1503+5G>A), identified in an Italian proband and her affected sibling, lies in the consensus sequence of the donor splice site of OCA2 intron 14 (IVS14+5G>A), in compound heterozygosity with a frameshift mutation, c.1450_1451insCTGCCCTGACA, which is predicted to determine the premature termination of the polypeptide chain (p.I484Tfs*19). In-silico prediction of the effect of the IVS14+5G>A mutation on splicing showed a score reduction for the mutant splice site and indicated the possible activation of a newly-created deep-intronic acceptor splice site. The second mutation is a synonymous transition (c.2139G>A, p.K713K) involving the last nucleotide of exon 20. This mutation was found in a young African albino patient in compound heterozygosity with a previously-reported OCA2 missense mutation (p.T404M). In-silico analysis predicted that the mutant c.2139G>A allele would result in the abolition of the splice donor site. The effects on splicing of these two novel mutations were investigated using an in-vitro hybrid-minigene approach that led to the demonstration of the causal role of the two mutations and to the identification of aberrant transcript variants.