Morgellons disease: a narrative review.

Morgellons disease is characterized by the persistent delusion of skin infestation, ultimately inflicting wounds and impairing quality of life. There is insufficient and conflicting research pertaining to this condition, imposing challenges on clinicians in understanding, diagnosing, and treating it. In this review, we summarize the available literature on Morgellons disease including its historical evolution, epidemiology, proposed pathophysiology, underlying structural and functional brain pathologies, typical and atypical clinical presentations, diagnosis, and treatment. A comprehensive review of the literature was conducted on PubMed, Embase, and Scopus using specified keywords. Selected articles were screened by two independent reviewers based on set inclusion and exclusion criteria. Conflicts were resolved by a third reviewer as needed. No limit to the date of selected articles was set due to the scarce literature available on the subject. Morgellons disease is an underdiagnosed entity, owing mostly to the lack of an established pathophysiology and treatment guidelines. While many authors classify it as a type of delusional infestation (DI), others correlate MD with an underlying spirochetal infection, namely Lyme disease. Neuroimaging studies have revealed abnormalities in the "fronto-striato-thalamo-parietal network", a finding common to patients with DI, in addition to alterations in structures related to the "Itch Processing Pathway". Patients tend to extract fibers from their skin lesions and place them in a match box hence the term "match box sign". The diagnosis is that of exclusion, requiring extensive work up to rule out secondary causes and differential diagnoses. Treatment is largely based on the use of antipsychotics, with or without cognitive behavioral therapy. Despite being a diagnosis of exclusion, clinicians must be aware of this entity and have a profound understanding of the pathogenesis underlying it. Upon clinical suspicion, secondary Morgellons should always be ruled out through a thorough history taking, physical examination, and laboratory exams. Despite the challenges brought by the heterogeneous presentation of the condition and the paucity of research revolving around it, the great impact that Morgellons disease has on patients' quality of life forms a pressing need for its adequate detection, diagnosis, and treatment.

Spondyloocular Syndrome: A Report of an Additional Family and Phenotypic Spectrum Delineation.

Spondyloocular syndrome (SOS, OMIM # 605822) is a rare genetic disorder characterized by osseous and ocular manifestations, including generalized osteoporosis, multiple long bones fractures, platyspondyly, dense cataracts and retinal detachment, and dysmorphic facial features, with or without short stature, cardiopathy, hearing impairment, and intellectual disability. Biallelic mutations in the XYLT2 gene (OMIM * 608125), encoding the xylosyltransferase II, were shown to be responsible for this disease. To date, 22 cases with SOS have been described, with varying clinical presentations and a yet-to-be-established genotypic-phenotypic correlation. Two patients from a consanguineous Lebanese family that presented with SOS were included in this study. Whole exome sequencing revealed a novel homozygous nonsense mutation in XYLT2 (p.Tyr414*) in these patients. We review all previously reported cases with SOS, describe the second nonsense mutation in XYLT2, and contribute to a better delineation of the phenotypic spectrum of the disease.

BHLHA9 homozygous duplication in a consanguineous family: A challenge for genetic counseling.

Split-hand/foot malformation (SHFM) with long-bone deficiency (SHFLD) is a rare condition characterized by SHFM associated with long-bone malformation usually involving the tibia. It includes three different types; SHFLD1 (MIM % 119,100), SHFLD2 (MIM % 610,685) and SHFLD3 (MIM # 612576). The latter was shown to be the most commonly reported with a duplication in the 17p13.1p13.3 locus that was narrowed down to the BHLHA9 gene. Here, we report a consanguineous Lebanese family with three members presenting with limb abnormalities including tibial hemimelia. One of these patients presented with additional bowing fibula and another with bilateral split hand. CGH array analysis followed by RQ-PCR allowed us to detect the first homozygous duplication on the short arm of chromosome 17p13.3 including the BHLHA9 gene and involved in SHFLD3. Interestingly, one patient with the homozygous duplicated region, carrying thus four BHLHA9 copies presented with long bone deficiency but no SHFM. The incomplete penetrance and the variable expressivity of the disease in this family as well as the presence of the BHLHA9 homozygous duplication rendered genetic counseling extremely challenging and preimplantation genetic diagnosis almost impossible.