BACKGROUND: The Triggering Receptor Expressed on Myeloid Cells 2 protein (TREM2) plays a crucial role in various biological processes, including osteoclast differentiation, and disease-associated microglia (DAM) activation to regulate neuroinflammation, and phagocytosis in the brain. Genetic variations in TREM2 are implicated in neurodegenerative disorders, such as Nasu-hakola disease (NHD), characterized by bone lesions, neuropsychiatric disorders, and early-onset dementia.
METHODS: We studied 3 siblings with suspected NHD. Whole-exome sequencing was conducted on the proband to identify the possible genetic cause(s) and by Sanger sequencing to validate the identified variants in the two other affected siblings, a healthy sister, and the parents.
RESULTS: We identified a novel homozygous deletion (c.549del; p.(Leu184Serfs*5)) in TREM2. Our literature review reveals 16 TREM2 mutations causing early-onset dementia and bone lesions.
CONCLUSIONS: These findings, alongside previous research, elucidate the clinical spectrum of TREM2-related diseases, aiding accurate diagnosis and patient care. This knowledge is vital for understanding TREM2-dependent DAM and its involvement in the pathogenesis of neurodevelopmental disorders which can help to develop targeted therapies and improve outcomes for TREM2-affected individuals.

Lipodystrophy syndrome is a medical condition characterized by the absence of adipose tissue without any underlying starvation or macromolecule breakdown. In HIV AIDS patients, the use of highly active antiretroviral therapy (HAART) can lead to an acquired form of lipodystrophy, with a prevalence ranging from 10% to 83% among HIV AIDS patients. It was aimed to review the current understanding of biological depiction and challenges related to lipodystrophy in AIDS patients. Relevant articles published in the English language were searched in PubMed, Google Scholar, and Google. Keywords used for the search were: lipodystrophy, lipodystrophy and HIV, ART and lipodystrophy, HIV treatment, metabolic syndrome and HIV. Articles with full abstract information were read for those that met the objective criteria of the review, then full text of the articles was accessed and used. It was revealed by the literature that patients who developed lipodystrophy are characterized by insulin abnormality, obesity, diabetes mellitus, dyslipidemia, fatty liver disease, and ovarian dysfunction. Anthropometric measurements have been known to change significantly with lipodystrophy. HIV patients suffering from hepatitis C virus, hepatitis B virus, who take a protease inhibitor, are changing treatment or duration of treatment, and are women are the common risk factors for lipodystrophy. The metabolic syndrome seen in HIV patients associated with lipodystrophy can further be complicated to different adverse health effects and can result in increased morbidity and mortality rate if not treated. Existing studies have successfully identified several challenges faced by HIV AIDS patients due to lipodystrophy, including low self-esteem, compromised quality of life, and poor treatment adherence. However, it is crucial to acknowledge that there may be numerous other challenges that have yet to be discovered, emphasizing the need for further studies. It is recommended that managing dyslipidemia, treating diabetes mellitus, modifying lifestyle, and improving the anthropometric measurements have crucial roles to halt further complications associated with lipodystrophy.

UNASSIGNED: Mandibuloacral dysplasia (MAD) syndrome is a rare genetic disease. Several progeroid syndromes including mandibuloacral dysplasia type A (MADA), mandibuloacral dysplasia type B(MADB), Hutchinson-Gilford progeria (HGPS) and mandibular hypoplasia, deafness, and lipodystrophy syndrome (MDPL) have been reported previously. A novel MAD progeroid syndrome (MADaM) has recently been reported. So far, 7 cases of MADaM diagnosed with molecular diagnostics have been reported in worldwide. In the Chinese population, cases of MAD associated with the MTX2 variant have never been reported.
UNASSIGNED: The clinical symptoms and the genetic analysis were identified and investigated in patients presented with the disease. In addition, we analyzed and compared 7 MADaM cases reported worldwide and summarized the progeroid syndromes reported in the Chinese population to date.
UNASSIGNED: The present study reports a case of a novel homozygous mutation c.378 + 1G > A in the MTX2 gene, which has not been previously reported in the literature. Patients present with early onset and severe symptoms and soon after birth are found to have growth retardation. In addition to the progeroid features, skeletal deformities, generalized lipodystrophy reported previously, and other multisystem involvement, e.g. hepatosplenic, renal, and cardiovascular system, this case was also reported to have combined hypogammaglobulinemia. She has since been admitted to the hospital several times for infections. Among 22 previously reported progeroid syndromes, 16/22 were MADA or HGPS caused by LMNA gene mutations, and the homozygous c.1579C > T (p.R527C) mutation may be a hot spot mutation for MAD in the Chinese population. MAD and HGPS mostly present in infancy with skin abnormalities or alopecia, MDPL mostly presents in school age with growth retardation as the first manifestation, and is often combined with an endocrine metabolism disorder after several decades.
UNASSIGNED: This is the first case of MAD syndrome caused by mutations in MTX2 gene reported in the Chinese population. MTX2 gene c.378 + 1G > A homozygous mutation has not been previously reported and the report of this patient expands the spectrum of MTX2 mutations. In addition, we summarized the genotypes and clinical characteristics of patients with progeroid syndromes in China.

The function of perilipin 1 in human metabolism was recently highlighted by the description of PLIN1 variants associated with various pathologies. These include severe familial partial lipodystrophy and early onset acute coronary syndrome. Additionally, certain variants have been reported to have a protective effect on cardiovascular diseases. The role of this protein remains controversial in mice and variant interpretation in humans is still conflicting. This literature review has two primary objectives (i) to clarify the function of the PLIN1 gene in lipid metabolism and atherosclerosis by examining functional studies performed in cells (adipocytes) and mice and (ii) to understand the impact of PLIN1 variants identified in humans based on the variant\'s location within the protein and the type of variant (missense or frameshift). To achieve these objectives, we conducted an extensive analysis of the relevant literature on perilipin 1, its function in cellular models and mice, and the consequences of its mutations in humans. We also utilized bioinformatics tools and consulted the Human Genetics Cardiovascular Disease Knowledge Portal to enhance the pathogenicity assessment of PLIN1 missense variants.

Radiesse® is a filler composed of calcium hydroxylapatite microspheres suspended in a carboxymethylcellulose gel (CaHA/CMC). It has robust rheological properties that have been associated with its versatility. CaHA/CMC is employed for both on-label indications of filling wrinkles or lines, volumizing, and contouring of areas as well as off-label indications aiming at biostimulation and skin tightening. However, despite the expanding use of CaHA/CMC, overall evidence and recommendations for treatment are currently lacking. This paper aims to provide an up-to-date overview of CaHA/CMC clinical applications, together with a level of evidence of supporting literature, focusing on the face. Based on the data, CaHA/CMC may be considered a safe and effective treatment option for cheeks, jawline, HIV-related facial lipoatrophy, and nasolabial folds. Treatment of marionette lines, chin, pre-jowl, and corner of the mouth also tends to respond with a high degree of efficacy. Despite the recent trend, guidelines, and safety profile of diluted and hyperdiluted Radiesse® , no randomized controlled trials have been published.

BACKGROUND: Lipodystrophy syndromes are a heterogeneous group of rare genetic or acquired disorders characterized by generalized or partial loss of adipose tissue. LMNA-related lipodystrophy syndromes are classified based on the severity and distribution of adipose tissue loss.
OBJECTIVE: We aimed to annotate all clinical and metabolic features of patients with lipodystrophy syndromes carrying pathogenic LMNA variants and assess potential genotype-phenotype relationships.
METHODS: We retrospectively reviewed and analyzed all our cases (n = 115) and all published cases (n = 379) curated from 94 studies in the literature.
RESULTS: The study included 494 patients. The most common variants in our study, R482Q and R482W, were associated with similar metabolic characteristics and complications though those with the R482W variant were younger (aged 33 [24] years vs 44 [25] years; P < .001), had an earlier diabetes diagnosis (aged 27 [18] vs 40 [17] years; P < .001) and had lower body mass index levels (24 [5] vs 25 [4]; P = .037). Dyslipidemia was the earliest biochemical evidence described in 83% of all patients at a median age of 26 (10) years, while diabetes was reported in 61% of cases. Among 39 patients with an episode of acute pancreatitis, the median age at acute pancreatitis diagnosis was 20 (17) years. Patients who were reported to have diabetes had 3.2 times, while those with hypertriglyceridemia had 12.0 times, the odds of having pancreatitis compared to those who did not.
CONCLUSIONS: This study reports the largest number of patients with LMNA-related lipodystrophy syndromes to date. Our report helps to quantify the prevalence of the known and rare complications associated with different phenotypes and serves as a comprehensive catalog of all known cases.

Lipodystrophy syndromes are characterized by a progressive metabolic impairment secondary to adipose tissue dysfunction and may have a genetic background. Congenital generalized lipodystrophy type 4 (CGL4) is an extremely rare subtype, caused by mutations in the polymerase I and transcript release factor (PTRF) gene. It encodes for a cytoplasmatic protein called caveolae-associated protein 1 (Cavin-1), which, together with caveolin 1, is responsible for the biogenesis of caveolae, being a master regulator of adipose tissue expandability. Cavin-1 is expressed in several tissues, including muscles, thus resulting, when dysfunctional, in a clinical phenotype characterized by the absence of adipose tissue and muscular dystrophy. We herein describe the clinical phenotypes of two siblings in their early childhood, with a phenotype characterized by a generalized reduction of subcutaneous fat, muscular hypertrophy, distinct facial features, myopathy, and atlantoaxial instability. One of the siblings developed paroxysmal supraventricular tachycardia leading to cardiac arrest at 3 months of age. Height and BMI were normal. Blood tests showed elevated CK, a mild increase in liver enzymes and triglycerides levels, and undetectable leptin and adiponectin concentrations. Fasting glucose and HbA1c were normal, while Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was mildly elevated. Both patients were hyperphagic and had cravings for foods rich in fats and sugars. Genetic testing revealed a novel pathogenic mutation of the CAVIN1/PTRF gene (NM_012232 exon1:c T21A:p.Y7X) at the homozygous state. The diagnosis of lipodystrophy can be challenging, often requiring a multidisciplinary approach, given the pleiotropic effect, involving several tissues. The coexistence of generalized lack of fat, myopathy with elevated CK levels, arrhythmias, gastrointestinal dysmotility, and skeletal abnormalities should prompt the suspicion for the diagnosis of CGL4, although phenotypic variability may occur.

BACKGROUND: Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome is a rare, hereditary, autoinflammatory disease. However, there are few cases reported in the literature. Therefore, we conduct this systematic review to summarize current evidence.
METHODS: We conducted a systematic search in July 2021 using 11 different electronic databases. The included articles were screened according to our inclusion and exclusion criteria and assessed using an appropriate quality assessment tool. Then, the relevant data were extracted and summarized in tables accordingly. Each step of the previous one was done by 3 independent reviewers, and the conflicts were resolved by discussion and sometimes by counseling a senior member.
RESULTS: The final included studies were 18 articles with 34 cases (mean age = 8 years, male/female = 19/15). The most reported symptoms and signs were fever 97.1%, erythematous plaques 76.5%, arthralgia 67.6%, hepatomegaly 61.8%, violaceous hue 61.8%, lipodystrophy in extremities 53.1% in addition to low weight and height. Rare features were reported too. The laboratories were not specific, which may be explained by a systemic inflammatory response. Vasculitis was the dominant feature in the skin biopsy, whereas the calcification in the basal ganglia was a prominent sign in many cases.
CONCLUSIONS: Fever, skin lesions, and systemic inflammatory response were the prominent features of chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome. The clinical picture is the main guide in addition to the pathological findings. Mutation detection is the confirmatory test. Prednisolone is the most effective reported treatment for acute presentations in the literature.

BACKGROUND: Involvement of subcutaneous tissue in idiopathic inflammatory myopathies (IIM) is poorly known.
METHODS: We conducted a systematic review of the literature regarding panniculitis and lipodystrophy/lipoatrophy in juvenile and adult IIM via PubMed/Medline, Embase and Scopus databases. Three local observations are included in this review. Epidemiological, clinical, paraclinical and therapeutic data were collected.
RESULTS: Panniculitis appears to be more common in adults than in juveniles. It was mainly localised in the upper and lower limbs. Panniculitis improved in most cases with steroids and panniculitis and myositis had a similar course in 83.3% and 72.2% of cases in juveniles and adults, respectively. Lipodystrophy appeared to be more frequent in juveniles and was only observed in dermatomyositis in both juveniles and adults. Lipodystrophy was mainly partial in juveniles and adults. The median time from myositis to the diagnosis of lipodystrophy was 6 years [0-35] and 2.5 years [0-10] in juveniles and adults, respectively. Lipodystrophy was associated with anti-TIF1 gamma auto-antibody positivity, a polycyclic/chronic course of myositis and the occurrence of calcinosis and might be an indicator of poor disease control.
CONCLUSIONS: Adipose tissue involvement, particularly lipodystrophy, occurs almost exclusively in dermatomyositis. The insidious onset and lack of awareness of the diagnosis may underestimate its prevalence. Larger studies are needed to identify possible risk factors in these patients, to better potential underlying pathophysiological process, in order to discuss potential therapeutic targets.

OBJECTIVE: Congenital generalized lipodystrophy (CGL) is a group of rare autosomal inherited diseases characterized by a widespread loss of adipose tissue. The main purpose of this study was to evaluate the features of Chinese patients with CGL2.
METHODS: Three patients diagnosed with CGL2 from our center were reviewed. Data on clinical features, results of laboratory analyses, and previous treatments were retrospectively collected. This study also reviewed studies that reported patients diagnosed with CGL2 in the last 30 years.
RESULTS: All patients presented a lack of subcutaneous fat, hypertriglyceridemia, reversed triangular faces, acanthosis nigricans, and hepatomegaly within the first six months of life. All three patients developed splenomegaly, and mental retardation in later life. Dietary control dramatically lowered triglyceride levels in all patients. One patient presented with diabetes mellitus at 1 year-old. Although combined therapy with low fat diet and metformin maintained normal levels of blood lipid and glucose, this patient developed hypertrophic cardiomyopathy at the age of three. By a literature review on all Chinese cases with CGL2, it is known that classic manifestations such as hypertriglyceridemia, hepatomegaly and diabetes mellitus can occur shortly after birth, and early diagnosis and treatment can improve quality of life. In this cohort, the most frequent variations are c.782dupG and c.974dup in the BSCL2 gene. However, the same genotype may have different clinical phenotypes in patients with CGL2.
CONCLUSIONS: This study not only described the clinical and genetic features of three patients with CGL2 in China, but also reviewed literature about CGL2 around the world.