Circulating Levels of MiRNAs From 320 Family in Subjects With Lipodystrophy: Disclosing Novel Signatures of the Disease.

Lipodystrophy (LD) indicates a group of rare disorders, with generalized or partial loss of white adipose tissue (WAT) often associated with metabolic derangements. Heterogeneity/wide spectrum of the disease and lack of biomarkers make diagnosis often difficult. MicroRNAs are important to maintain a correct WAT function and WAT is a source of circulating miRNAs (cmiRs). miRNAs from 320 family were previously detected in the WAT and variably associated to the metabolic syndrome. Our aim was then to investigate if LD can result in altered abundance of cmiRs-320. We collected samples from a cohort of LD subjects of various subtypes and from age matched controls. Use of quantitative PCR determined that cmiRs- 320a-3p, 320b, 320c, 320e are upregulated, while 320d is downregulated in LD. CmiRs-320 power as classifiers was more powerful in the most extreme and defined forms of LD, including the generalized and the Dunnigan subtypes. cmiR-320a-3p showed significant inverse relationships with plasma leptin (P < 0.0001), typically low in LD. The hepatic enzymes gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the marker of inflammation C-reactive protein (CRP) were inversely related to cmiR 320d (P < 0.05, for CRP and GGT; P < 0.01, for AST and ALT). Gene ontology analysis revealed cell-cell adhesion as a process regulated by 320 miRNAs targets, thus disclosing a novel route to investigate origin of WAT loss/dysfunction. In conclusion, cmiRs-320 constitute novel biomarkers of LD, abundance of miR320a-3p is inversely associated to indicators related to WAT function, while downregulation of cmiR-320d predicts an altered hepatic profile and higher inflammation.

Partial Lipodystrophy and LMNA p.R545H Variant.

Laminopathies are disorders caused by LMNA gene mutations, which selectively affect different tissues and organ systems, and present with heterogeneous clinical and pathological traits. The molecular mechanisms behind these clinical differences and tissue specificity have not been fully clarified. We herein examine the case of a patient carrying a heterozygous LMNA c.1634G>A (p.R545H) variant with a mild, transient myopathy, who was referred to our center for the suspicion of lipodystrophy. At physical examination, an abnormal distribution of subcutaneous fat was noticed, with fat accumulation in the anterior regions of the neck, resembling the fat distribution pattern of familial partial lipodystrophy type 2 (FPLD2). The R545H missense variant has been found at very low allelic frequency in public databases, and in silico analysis showed that this amino acid substitution is predicted to have a damaging role. Other patients carrying the heterozygous LMNA p.R545H allele have shown a marked clinical heterogeneity in terms of phenotypic body fat distribution and severity of organ system involvement. These findings indicate that the LMNA p.R545H heterozygous variant exhibits incomplete penetrance and highly variable expressivity. We hypothesized that additional genetic factors, epigenetic mechanisms, or environmental triggers might explain the variable expressivity of phenotypes among various patients.

Blepharophimosis, Ptosis, Epicanthus Inversus Syndrome: New Report with a 197-kb Deletion Upstream of FOXL2 and Review of the Literature.

Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is due to heterozygous FOXL2 intragenic mutations in about 70% of the patients, whereas total or partial gene deletions account for a minority of cases. Alteration of FOXL2 regulatory elements has been rarely described in patients with BPES. In this study, a prepubertal girl with BPES due to a 197-kb de novo deletion of the regulatory elements upstream of FOXL2 is reported. This girl presented with additional clinical features such as a soft cleft palate and microcephaly; thus, this copy number variant might have other somatic effects. The present deletion encompasses 2 coding genes (MRPS22 and COPB2), whose homozygous mutations have been associated with microcephaly. In our case, the sequences of the non-deleted allele were normal, ruling out a compound genetic defect. Normal levels of new biomarkers of ovarian reserve (anti-müllerian hormone, inhibin B) likely indicate an early diagnosis of type 2 BPES, but an evolutive gonadal damage will be excluded only by long-term follow-up. Additional reports of microdeletions upstream of FOXL2 are needed to better define the underlying genetic mechanism and the related phenotypic spectrum; the ability of the new hormonal markers to predict ovarian function in adolescence and adulthood should be confirmed.

Cleft Lip and Palate Repair.

INTRODUCTION: Cleft lip and palate is the most frequent congenital craniofacial deformity. In this article, the authors describe their experience with cleft lip and palate repair. METHODS: Data regarding patients presenting with primary diagnosis of cleft lip and/or palate, between 2009 and 2015, were reviewed. Details including demographics, type of cleft, presence of known risk factors, surgical details, and follow-up visits were collected. Documented complications were reported. Caregivers' satisfaction was assessed with a survey. The survey used to assess satisfaction with cleft-related features was based on the cleft evaluation profile (CEP). In addition, 4 assessors used visual analog scale (VAS) to assess the aesthetic satisfaction. RESULTS: Seven hundred fifty-two patients with primary diagnosis of cleft lip and/or palate underwent surgical correction at "S. Chiara" Hospital, 432 (57.45%) male and 320 (42.55%) female. The most common cleft types in our study were incomplete cleft palate (152 patients) and left unilateral complete cleft lip and palate (152 patients). Associated syndromes were found in 46 patients (6.12%). Cleft lip was repaired using a modified Tennison-Randall technique when the defect was unilateral, whereas a modified Mulliken technique was used for bilateral cleft lip. Cleft palate was repaired using the Bardach technique or Von Langenbeck technique at 5 to 6 months of age. Cleft lip and palate was repaired in several surgical steps. In total, complications were reported in 81 of 752 patients (14.16%). Average fathers' satisfaction score assessed using CEP was 4.5 (lip), 4.8 (nose), 4.7 (teeth), 4.8 (bite), 4.2 (breathing), 4.6 (profile). Average mothers' satisfaction score assessed using CEP was 4.3 (lip), 4.6 (nose), 4.4 (teeth), 4.5 (bite), 4.1 (breathing), 4.4 (profile). Average level of aesthetic satisfaction, assessed using VAS, was 8.7 (fathers), 8.1 (mothers), 7.9 (lay person), and 8.0 (senior cleft surgeon). CONCLUSION: The multidisciplinary management of children with oral cleft determinated good results, in terms of satisfaction and aesthetic appearance. From our experience, periosteoplasty and lip-adhesion are key surgical techniques.

Popliteal Pterygium Syndrome With Syngnathia.

Popliteal pterygium syndrome is a condition characterized by skin webs on the popliteal fossa, which may impair mobility unless surgically repaired. Affected individuals may also have syndactyly on the fingers and/or toes. Most people with this disorder present cleft lip and cleft palate and they can have syngnathia, that is a congenital adhesion between maxilla and mandible by fibrous bands, which affects the opening of the mouth. The case that we report is about a 2-month-old male, who presented skin webs bilaterally on the popliteal fossa, syndactyly between the IV and the V toe of the right foot and between the III and the IV toe of the left foot, and genital malformations. He was born with complete bilateral cleft lip and complete cleft palate on the left side and incomplete cleft palate on the right side and syngnathia with 4 fibrous bands between the mandibular arch and the maxilla arch on the right side, which affected the opening of the mouth. The case of our patient is very interesting because there have been few reported patients affected by popliteal pterygium syndrome with syngnathia.

Deforming Mucocutaneous Leishmaniasis of the Nose.

The authors present a clinical report of deforming mucocutaneous leishmaniasis of the nose in a native American woman, left untreated for 25 years. The nose was reconstructed using the local tissue displaced as flaps, and using cartilage grafts taken from the nasal septum and the ear shell. To the best of the authors' knowledge, the literature offers just 1 report on a similar patient.

Malignant melanoma of the nasal septum.

Primary malignant melanoma involving the nasal and paranasal sinus mucosa is a rare neoplasm, accounting for less than 1% of all melanomas. Being more aggressive than its cutaneous counterpart, it carries a poor prognosis. We report a case arising from the nasal septum mucosae in a 78-year-old man. We describe clinical features, diagnosis, and treatment of this rare disease along with a review of the pertinent literature. Endoscopic resection of the neoplasm was performed, enabling diagnosis of sinonasal mucosal melanoma involving the frontal sinus floor. Because the patient was too compromised to achieve radical surgical approach (craniofacial resection), he underwent radiation therapy. Through this article, we wish to emphasize that early diagnosis with a high index of suspicion is critical because this type of tumor is extremely aggressive. Its location and relatively nonspecific features frequently delay diagnosis, and its rarity avoids an optimal treatment guideline setting.