The face of Non-photosensitive trichothiodystrophy phenotypic spectrum: A subsequent study on paediatric population.

BACKGROUND: Non-photosensitive trichothiodystrophies (TTDs) are a diverse group of genodermatoses within the subset of conditions known as "sulphur-deficient brittle hair" syndromes. A part of them has only recently been identified, revealing novel causative genes and very rare phenotypes of these genetic skin disorders. At the same time, the molecular basis of previously published and unresolved cases has been revealed through the introduction of innovative genetic techniques. We have previously described the facial phenotype of patients with the Photosensitive form of TTD during childhood. This study marks the beginning of an effort to expand the analysis to include individuals of the same age who do not have photosensitivity. METHODS: A total of 26 facial portraits of TTD paediatric patients with Non-photosensitivity from the literature were analysed using computer-aided technologies, and their facial features were examined through a detailed clinical review. RESULTS: Distinct facial features were identified in both Photosensitive and Non-photosensitive TTDs. CONCLUSION: The present study has comprehensively elucidated the facial features in TTDs, encompassing the Non-photosensitive clinical spectrum.

Pathogenic variants in KMT2C result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes.

Trithorax-related H3K4 methyltransferases, KMT2C and KMT2D, are critical epigenetic modifiers. Haploinsufficiency of KMT2C was only recently recognized as a cause of neurodevelopmental disorder (NDD), so the clinical and molecular spectrums of the KMT2C-related NDD (now designated as Kleefstra syndrome 2) are largely unknown. We ascertained 98 individuals with rare KMT2C variants, including 75 with protein-truncating variants (PTVs). Notably, ∼15% of KMT2C PTVs were inherited. Although the most highly expressed KMT2C transcript consists of only the last four exons, pathogenic PTVs were found in almost all the exons of this large gene. KMT2C variant interpretation can be challenging due to segmental duplications and clonal hematopoesis-induced artifacts. Using samples from 27 affected individuals, divided into discovery and validation cohorts, we generated a moderate strength disorder-specific KMT2C DNA methylation (DNAm) signature and demonstrate its utility in classifying non-truncating variants. Based on 81 individuals with pathogenic/likely pathogenic variants, we demonstrate that the KMT2C-related NDD is characterized by developmental delay, intellectual disability, behavioral and psychiatric problems, hypotonia, seizures, short stature, and other comorbidities. The facial module of PhenoScore, applied to photographs of 34 affected individuals, reveals that the KMT2C-related facial gestalt is significantly different from the general NDD population. Finally, using PhenoScore and DNAm signatures, we demonstrate that the KMT2C-related NDD is clinically and epigenetically distinct from Kleefstra and Kabuki syndromes. Overall, we define the clinical features, molecular spectrum, and DNAm signature of the KMT2C-related NDD and demonstrate they are distinct from Kleefstra and Kabuki syndromes highlighting the need to rename this condition.

Evaluation of the facial profile of skeletal Class III patients undergoing camouflage orthodontic treatment: a retrospective study.

Objective: To identify objective metrics for evaluating the esthetics of facial profiles in skeletal Class III patients undergoing camouflage orthodontic treatment. Methods: Eighty Asian-Chinese patients classified as skeletal Class III were included. Thirty cephalometric measurements of pre- and posttreatment cephalograms were analyzed. Ten orthodontists assigned visual analog scale (VAS) scores to the pre- and posttreatment profiles based on standardized lateral photographs. Correlations between subjective VAS scores and objective measurements were assessed using Pearson correlation and stepwise multiple linear regression analysis. Results: Lower incisor (L1) protrusion, nasolabial angle, lower lip-E line distance, SNB angle, and L1 to AP plane were significantly correlated with VAS scores of pretreatment profiles of skeletal Class III patients. Factors such as retraction of the lower incisor, increased interincisal angle and overjet, reduction of lower lip-E line distance, as well as augmentation of the Z angle and nasolabial angle were significantly correlated with the changes in VAS scores post-camouflage orthodontic treatment. Stepwise multiple linear regression analysis revealed that pretreatment nasolabial angle, changes in the lower lip-E line distance, and pretreatment Pog-NB distance were the key factors influencing the posttreatment facial profile esthetics of skeletal Class III patients with camouflage orthodontic treatment. Conclusion: Several cephalometric measurements correlate with subjective facial esthetic evaluations of skeletal Class III patients. Changes in lower lip prominence, the pretreatment nasolabial angle, and Pog-NB distance are the main factors related to facial esthetics in skeletal Class III patients after camouflage orthodontic treatment.

Facial Hyperpigmentation: A Rare Side Effect of Adalimumab.

This report describes a case of facial hyperpigmentation in a patient with Crohn's disease receiving adalimumab, a tumor necrosis factor (TNF)-alpha inhibitor. The onset of hyperpigmentation coincided with adalimumab administration, and its discontinuation resulted in significant improvement. Histopathological findings suggest a postinflammatory process at the dermo-epidermal junction. However, the precise mechanism remains unclear.

Photographic grading to evaluate facial cleanliness and trachoma among children in Amhara region, Ethiopia.

BACKGROUND: Promotion of facial cleanliness is recommended for the elimination of blinding trachoma, largely because of observational studies that have found an association between various measures of facial uncleanliness and trachoma. However, when a field grader assesses both facial cleanliness and trachoma, associations may be biased. Assessment of photographs of the face and conjunctiva by masked graders may provide a less biased estimate of the relationship between facial cleanliness and trachoma. METHODS: Face photographs, conjunctival photographs, and conjunctival swabs were obtained on a random sample of 0-9-year-old children from each of 40 communities in Amhara region, Ethiopia. Face photographs were assessed for the presence of seven measures of an unclean face (i.e., wet nasal discharge, dry nasal discharge, wet ocular discharge, dry ocular discharge, food, dust/dirt, and flies) by three independent masked photo-graders. Conjunctival photographs were similarly graded in a masked fashion for signs of clinically active trachoma. Conjunctival swabs were processed for Chlamydia trachomatis DNA. RESULTS: Of 2073 children with complete data, 808 (39%) had evidence of clinically active trachoma, 150 (7%) had evidence of ocular chlamydia infection, and 2524 (91%) had at least one measure of an unclean face. Dry ocular discharge had the strongest association with clinically active trachoma (age- and sex-adjusted prevalence ratio [PR] 1.4, 95% CI 1.2-1.6) and ocular chlamydia infection (PR 1.9, 95%CI 1.3-2.9), although significant associations were observed between each of the measures of facial uncleanliness and trachoma. CONCLUSIONS: Masked assessment of face and conjunctival photographs confirmed prior observational studies that have noted associations between various measures of facial uncleanliness and trachoma. The causal relationship between facial uncleanliness and trachoma is unclear since many features used to measure facial cleanliness (e.g., ocular discharge, nasal discharge, and flies) could be consequences of antecedent ocular chlamydia infection. TRIAL REGISTRATION: NCT02754583, clinicaltrials.gov.

Pseudolymphomatous Cutaneous Angiosarcoma Presenting With Persistent Firm Facial Edema in a Patient With Systemic Sclerosis.

ABSTRACT: Pseudolymphomatous cutaneous angiosarcoma (cAS) is a rare subtype characterized by a prominent lymphocytic infiltrate, posing diagnostic challenges due to its resemblance to lymphoid neoplastic processes. We present a novel case highlighting the clinical and histopathological features, notably its association with persistent firm facial edema in a patient with systemic sclerosis (SSc). A 47-year-old woman with a 21-year history of SSc presented with firm palpebral edema evolving to involve the entire face and cervical region over six months. Diagnostic imaging revealed inflammatory changes in orbital regions, supradiaphragmatic lymphadenopathies, and lytic lesions. Skin biopsy demonstrated a diffuse neoplasm with vascular channels and solid areas, accompanied by dense lymphocytic proliferation. Pseudolymphomatous cutaneous angiosarcoma, a rare malignant neoplasm, exhibits variable clinical presentations and rapid progression. Histologically, it manifests as irregularly shaped vascular channels lined by prominent endothelial cells. Immunohistochemistry, particularly markers such as v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG), aids in diagnosis. Notably, this case marks the first presentation of cAS with persistent facial edema in SSc, highlighting the association between SSc and cancer risk. This case underscores the diagnostic challenges posed by cAS and emphasizes the importance of early detection for optimal patient outcomes. Further understanding of its association with autoimmune disorders such as SSc is crucial for comprehensive management strategies.

A survey of 701 cases of tinea faciei in Hangzhou, southeastern China, from 2018 to 2023.

BACKGROUND: Tinea faciei, a specific dermatophytosis that affects the glabrous skin of the face, not only causes physical discomfort but also leads to greater psychological distress. Tinea faciei is a public health concern. OBJECTIVES: To analyse the epidemiological characteristics, responsible dermatophyte species and clinical features of tinea faciei in Hangzhou. METHODS: Data were obtained from the Laboratory Information System of the Mycology Laboratory and Medical Information System at a hospital in Hangzhou. Isolates were identified based on their macroscopic appearance and microscopic morphology. RESULTS: Tinea faciei was diagnosed in 701 patients, involving 359 males and 342 females, aged between 2 months and 97 years. In total, 499 isolates (71.18%) were identified as Trichophyton rubrum. Anthropophilic isolates were identified in 297 (82.73%) males and 207 (60.53%) females (p < .01). Among patients with anthropophilic dermatophytes infection, 447 (88.69%) were adults. Zoophilic dermatophytes were isolated in 57 (15.88%) males and 130 (38.01%) females (p < .01), among whom 108 (57.75%) were children. CONCLUSIONS: Anthropophilic dermatophytes, especially T. rubrum, were the predominant cause of tinea faciei, while zoophilic dermatophytes were the most prevalent in children. Compared with men, women may be more susceptible to zoophilic dermatophytes.

Porcine-derived Acellular Dermal Matrix for Temporary Soft Tissue Coverage in Locally Advanced Angiosarcoma of the Face - A Soft Tissue Odyssey?

BACKGROUND/AIM: Angiosarcomas of the face are rare but present significant treatment challenges due to their origin in the supportive tissues of blood or lymphatic vessels. Achieving optimal balance between oncological efficacy and aesthetic outcomes requires a multidisciplinary approach, particularly in cases where radical R0 resection is necessary. Delays often occur, especially during histopathological examinations, which can complicate primary plastic reconstruction before definitive pathological findings. CASE REPORT: To address this issue, we present a case with the use of porcine-derived acellular dermal matrix for temporary soft tissue coverage as a viable option in a case of angiosarcoma of the face. This is particularly useful in situations where frozen sections risk the loss of critical anatomical structures and intraoperative diagnosis is not feasible. This approach allowed for satisfactory wound coverage and granulation during diagnostic phases, paving the way for oncologically manageable situations and functional rehabilitation. CONCLUSION: Temporary soft tissue coverage with porcine-derived acellular dermal matrix is a valuable option in tumor surgery of rare and complex situations.

DPF2-related Coffin-Siris syndrome type 7 in two generations.

To date 11 patients with Coffin-Siris syndrome type 7 (OMIM 618027) have been described since the first literature report. All reported patients carried de novo variants with presumed dominant negative effect, which localized in the PHD1/PHD2 domains of DPF2. Here we report on the first familial case of Coffin-Siris syndrome type 7. The index patient presented during the 1st year of life with failure to thrive and ectodermal anomalies. The genetic analysis using whole exome sequencing showed a likely pathogenic missense variant in the PHD1 region. The family analysis showed that the mother as well as the older brother of the index patient also carried the detected DPF2 variant in heterozygous state. The mother had a history of school difficulties but no history of failure to thrive and was overall mildly affected. The brother showed developmental delay with autistic features, ectodermal anomalies and overlapping morphologic features but did not have a history of growth failure problems. To our knowledge this is the first report of an inherited likely pathogenic variant in DPF2, underlining the variability of the associated phenotype as well as the importance of considering inherited DPF2 variants during the variant filtering strategy of whole exome data.

Acute upper airway obstruction due to cervical hematoma after cervicofacial liposuction.

Liposuction is a surgical procedure performed worldwide. Although many fatal complications of liposuction have been reported, to our knowledge, no cases of fatal liposuction complications specifically related to the face region have been reported. Here, we present a case of a woman in her 30s who developed a cervical hematoma and upper airway obstruction following facial liposuction. We present this unique case to highlight the rare occurrence of fatal complications specific to facial liposuction. The patient underwent liposuction during surgery at a cosmetic surgical clinic and awoke from anesthesia after the procedure. Two hours later, she developed a neck swelling and dyspnea. While the anesthesiologist managed her airway, she went into cardiopulmonary arrest. She was then transferred to the emergency room but died on day 7 of hospitalization. The autopsy revealed swelling of the right cheek and mandible, a subcutaneous hematoma in the same area, and laryngeal edema. A damaged facial artery branch was identified, which was consistent with the computed tomography (CT) findings on admission. CT also showed that the hematoma compressed the right internal jugular vein, suggesting that venous outflow impairment caused by the hematoma may have exacerbated the airway obstruction. This case reveals that cervical hematoma caused by facial liposuction can cause fatal upper airway obstruction and the onset of the hematoma may be gradual.

Expanding the clinical spectrum of Coffin-Siris syndrome with anorectal malformations: Case report and review of the literature.

Anorectal malformations (ARMs) represent a wide spectrum of congenital anomalies of the anus and rectum, of which more than half are syndromic. Their etiology is highly heterogeneous and still poorly understood. We report a 4-year-old girl who initially presented with an isolated ARM, and subsequently developed a global developmental delay as part of an ARID1B-related Coffin-Siris syndrome (CSS). A co-occurrence of ARMs and CSS in an individual by chance is unexpected since both diseases are very rare. A review of the literature enabled us to identify 10 other individuals with both CSS and ARMs. Among the ten individuals reported in this study, 8 had a variant in ARID1A, 2 in ARID1B, and 1 in SMARCA4. This more frequent than expected association between CSS and ARM indicates that some ARMs are most likely part of the CSS spectrum, especially for ARID1A-related CSS.

A rare case of facial cutaneous Rosai-Dorfman disease clinically mimicking basal cell carcinoma followed by multiple myeloma after 2 years.

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis disorder characterized by the proliferation of histiocytes within the lymph nodes. Extranodal involvement can occur; however, only 10% of extranodal RDD involve the skin. We present a unique case of a 66-year-old woman with cutaneous RDD followed by the development of multiple myeloma (MM). To our knowledge, this is only the second reported case where RDD preceded a diagnosis of MM, with the first documented instance occurring in 2018. The patient presented to the dermatology clinic with a 5-year history of painless, solitary lesion over the right cheek. Local examination revealed a single 6 mm x 7 mm well-circumscribed pearly telangiectatic lesion resembling basal cell carcinoma over the right nasolabial fold and cheek. The lesion was excised with a 3 mm circumferential margin. Histopathology showed a mixed lymphohistiocytic cell infiltrate with emperipolesis and immunohistochemical staining patterns consistent with RDD. Two years later, the patient presented with hip pain and was diagnosed with MM. She was treated with lenalidomide, bortezomib, and dexamethasone, and was later maintained on lenalidomide. Our case adds to the limited evidence suggesting a potential association between RDD and MM. Further research in this field is required to promptly identify and manage patients with such a presentation in the future.

In the face and neck, keloid scar distribution is related to skin thickness and stiffness changes associated with movement.

Keloid scars tend to occur in high-tension sites due to mechanical stimuli that are involved in their development. To date, a detailed analysis of keloid distribution focused specifically on facial and neck areas has not been reported, and limited literature exists as to the related mechanical factors. To rectify this deficiency of knowledge, we first quantified the facial and neck keloid distribution observed clinically in 113 patients. Subsequently, we performed a rigorous investigation into the mechanical factors and their associated changes at these anatomic sites in healthy volunteers without a history of pathologic scarring. The association between keloid-predilection sites and sebaceous gland-dense and acne-prone sites was also examined. To assess skin stretch, thickness and stiffness, VECTRA, ultrasound and indentometer were utilised. Baseline skin stiffness and thickness were measured, as well as the magnitude of change in these values associated with facial expression and postural changes. Within the face and neck, keloids were most common near the mandibular angle (41.3%) and lateral submental (20.0%) regions. These areas of increased keloid incidence were not associated with areas more dense in sebaceous glands, nor linked consistently with acne-susceptible regions. Binomial logistic regression revealed that changes in skin stiffness and thickness related to postural changes significantly predicted keloid distribution. Skin stiffness and thickness changes related to prolonged mechanical forces (postural changes) are most pronounced at sites of high keloid predilection. This finding further elucidates the means by which skin stretch and tension are related to keloid development. As a more detailed analysis of mechanical forces on facial and neck skin, this study evaluates the nuances of multiple skin-mechanical properties, and their changes in a three-dimensional framework. Such factors may be critical to better understanding keloid progression and development in the face and neck.

Identification of a novel phenotype of external ear deformity related to Coffin-Siris syndrome-9 and literature review.

De novo germline variants of the SRY-related HMG-box 11 gene (SOX11) have been reported to cause Coffin-Siris syndrome-9 (CSS-9), a rare congenital disorder associated with multiple organ malformations, including ear anomalies. Previous clinical and animal studies have found that intragenic pathogenic variant or haploinsufficiency in the SOX11 gene could cause inner ear malformation, but no studies to date have documented the external ear malformation caused by SOX11 deficiency. Here, we reported a Chinese male with unilateral microtia and bilateral sensorineural deafness who showed CSS-like manifestations, including dysmorphic facial features, impaired neurodevelopment, and fingers/toes malformations. Using trio-based whole-exome sequencing, a de novo missense variant in SOX11 (NM_003108.4: c.347A>G, p.Y116C) was identified and classified as pathogenic variant as per American College of Medical Genetics guidelines. Moreover, a systematic search of the literature yielded 12 publications that provided data of 55 SOX11 intragenic variants affecting various protein-coding regions of SOX11 protein. By quantitatively analyzing phenotypic spectrum information related to these 56 SOX11 variants (including our case), we found variants affecting different regions of SOX11 protein (high-mobility group [HMG] domain and non-HMG regions) appear to influence the phenotypic spectrum of organ malformations in CSS-9; variants altering the HMG domain were more likely to cause the widest range of organ anomalies. In summary, this is the first report of CSS with external ear malformation caused by pathogenic variant in SOX11, indicating that the SOX11 gene may be not only essential for the development of the inner ear but also critical for the morphogenesis of the external ear. In addition, thorough clinical examination is recommended for patients who carry pathogenic SOX11 variants that affect the HMG domain, as these variants may cause the widest range of organ anomalies underlying this condition.

Regional odontodysplasia with facial cellulitis: a case report and literature review.

Regional odontodysplasia (ROD) is a localized developmental anomaly involving deciduous and permanent dentition, with a significant impact on patients. The affected teeth display unique ghost-like radiological characteristics, clinically manifesting as delayed tooth eruption, abnormal tooth morphology, and recurrent swelling of gingiva. In this paper, we report a case of a 2-year-old patient with ROD whose chief complaint was facial cellulitis. We analyze the medical history, clinical examination, radiographic findings, and histologic findings, and review the pathological features, pathogenesis, multidisciplinary diagnosis, and treatment of ROD. This rare case, which offers clinical samples for its further study, can provide a deeper study of ROD.

Facial and systemic mucormycosis caused by Lichtheimia corymbifera in a goat: case report and literature review of fungal infections in goats.

An 8-y-old Pygora doe was presented to the University of California-Davis, Veterinary Medical Teaching Hospital because of non-healing facial swelling of 2-wk duration. The lesion grew despite medical treatment, causing discomfort masticating, little-to-no airflow from the right nasal passage, and led to euthanasia. On gross examination, a large facial mass with a draining tract through the skin and hard palate was identified. On section, the mass was brown-pink, homogeneous, and friable. Abscess-like masses were identified in the lungs and kidney. Histopathology of the face, including oral and nasal cavities, salivary glands, and lymph nodes, as well as the lung and kidney lesions, revealed large areas of necrosis with numerous wide ribbon-like, mostly aseptate, fungal hyphae consistent with zygomycetes. PCR for fungal organisms performed on formalin-fixed, paraffin-embedded tissue from the face identified Lichtheimia corymbifera (formerly Absidia corymbifera) of the order Mucorales and an Aspergillus sp. The lesion was suspected to have started either as a fungal rhinitis or dental feed impaction, subsequently spreading to the face and systemically to the lungs and kidney. We describe here the lesions associated with facial mucormycosis in a goat and present a literature review of L. corymbifera infection in veterinary species and fungal infections in goats.

Clinical, imaging, and pathological characteristics of congenital infiltrating lipomatosis of the face.

Congenital infiltrating lipomatosis of the face (CILF) is a rare congenital disease of the head and neck region. In this study, the cases of 20 patients diagnosed with CILF were reviewed retrospectively to analyse the characteristics of the disease. The symptoms, signs, and clinical progression were investigated. Radiological changes were analysed according to the distribution of the trigeminal nerve. The pathological features of the fatty facial lesions, jaw hyperplasia, and lingual lesions were further identified. All 20 patients demonstrated hemifacial hypertrophy at birth. None had a family history of the disease. Significant radiological features of CILF (prevalence ≥90%) included thickened buccal subcutaneous fat, palatal submucosal fat, and temporal subcutaneous fat, maxillary tuberosity heteroplasia, and fatty infiltration of the masseteric intermuscular space. With regard to the trigeminal nerve, the frontal branch region (CNV1) was rarely affected, while the maxillary (CNV2) and mandibular (CNV3) branch regions showed considerable changes. Pathologically, CILF was observed to be characterized by the infiltration of mature adipose tissue into the adjacent buccal soft tissue, osteal remodelling surrounded by sheets of mature lipocytes and supporting fibrovascular stroma, and lingual hamartoma. In summary, CILF exhibits distinct characteristics that are related to the regions controlled by the maxillary and mandibular branches of the trigeminal nerve, suggesting that CILF may be associated with early neural development.

Genetic Basis of Pigment Dispersion Syndrome and Pigmentary Glaucoma: An Update and Functional Insights.

Pigment Dispersion Syndrome (PDS) and Pigmentary Glaucoma (PG) comprise a spectrum of ocular disorders characterized by iris pigment dispersion and trabecular meshwork changes, resulting in increased intraocular pressure and potential glaucomatous optic neuropathy. This review summarizes recent progress in PDS/PG genetics including rare pathogenic protein coding alterations (PMEL) and susceptibility loci identified from genome-wide association studies (GSAP and GRM5/TYR). Areas for future research are also identified, especially the development of efficient model systems. While substantial strides have been made in understanding the genetics of PDS/PG, our review identifies key gaps and outlines the future directions necessary for further advancing this important field of ocular genetics.