Reductive Otoplasty and Facial Debulking in a Pediatric Patient With PIK3CA-Related Overgrowth

Overgrowth syndromes encompass a number of rare genetic diseases with heterogeneous clinical phenotypes. Accordingly, there is a strong imperative to collect data and classify these disorders to aid in diagnosis and management. Recent advances in the genetics of overgrowth syndromes have identified mutations in the PIK3CA gene. These somatic mutations manifest in progressive segmental overgrowth of fibrous and adipose tissue and bone, vascular malformations, and in some cases, increased risk for malignancy. Targeted medical therapy is under investigation for the management of PROS, but treatment of overgrowth relies on surgical debulking. Macrotia in PIK3CA-related overgrowth spectrum (PROS) has not been reported in the literature. In this case, we discuss a novel approach to reductive otoplasty and facial soft tissue debulking in a pediatric patient with PROS.

Case Report: Occupational therapy in a patient with an overgrowth syndrome that restricts movement

Background: Overgrowth syndromes are a heterogeneous group of conditions characterized by excessive body growth - localized or generalized - commonly associated with various malformities and an increased oncological risk. Case report: Here we present the case of a 59-years old man, employed in an office, who suffers from an asymmetric overgrowth of the lower limbs. Currently the patient presents malformations of the lower left limb (hip, knee and ankle), evident on the articular and periarticular level, where there are diffuse exostoses. This case discusses the main occupational concerns relating to the patient’s workspace at a high floor level that could create critical issues in the event of an emergency exodus. Given the impossibility of placing the patient in heavy manual activities, employment is limited to office activities. Adjustments were carried out at the patient’s workstation, and thus the patient has been recognized as fit to work. Increased frequency of breaks were prescribed in order to allow the physiological alternation of postures. Conclusions: In cases of overgrowth syndromes, the exact identification of the limitations presented by the patient and observations about ambulatory functions must be carefully evaluated in order to modulate the work environment.

Lymphatic Malformation Responsive to Sirolimus in Keratinocytic Epidermal Nevus Syndrome with KRAS Mutation: A Case and Brief Literature Discussion

We present a rare case of KRAS keratinocytic epidermal nevus syndrome with lymphatic malformation, responsive to treatment with sirolimus, an mTOR inhibitor. A brief review of the current literature regarding sirolimus use in vascular malformations, lymphatic malformations, regional overgrowth syndromes, and RASopathies is discussed.

Overgrowth Syndrome and Multi-Stage Reconstruction of Hand and Feet Deformations

A case of asymmetric overgrowth of feet, fingers and toes is presented and the performed diagnostic and multi-stage surgical reconstruction described. The condition in hands and feet was already present at birth. The hypertrophic growth advanced progressively, and histological investigation of the affected tissues revealed no pathology. The examination of inner organs, skin, subcutaneous tissue, nerves and vessels showed no deviations, the girl's karyotype was normal, 46 xx, no mosaicism was confirmed. In view of the new diagnostic criteria, this case cannot be assigned to any of the overgrowth syndromes. The most suitable classification would be in the group of Proteus-like syndrome. At this time only isolated hypertrophy of soft tissues and skeleton is present. According to the data from the literature, later development of anomalies is possible, so Proteus-like syndrome cannot be completely excluded.

Focal Fibroadipose Overgrowth of the Forehead: A Case Report

This article describes a rare case of isolated focal fibroadipose overgrowth of the forehead in a 15-year-old patient. Various overgrowth syndromes were considered in the differential diagnosis, including Proteus syndrome, facial infiltrating lipomatosis, and macrodystrophia lipomatosa. The diagnosis is primarily based on clinical presentation and imaging modalities. However, for academic and supporting diagnostic purposes a biopsy is advised, yet may not be in the best interest of the patient. Management was conservative with future perspective for surgical management after cessation of growth.

HSF1 physically neutralizes amyloid oligomers to empower overgrowth and bestow neuroprotection

The role of proteomic instability in cancer, particularly amyloidogenesis, remains obscure. Heat shock factor 1 (HSF1) transcriptionally governs the proteotoxic stress response to suppress proteomic instability and enhance survival. Paradoxically, HSF1 promotes oncogenesis. Here, we report that AKT activates HSF1 via Ser230 phosphorylation. In vivo, HSF1 enables megalencephaly and hepatomegaly, which are driven by hyperactive phosphatidylinositol 3-kinase/AKT signaling. Hsf1 deficiency exacerbates amyloidogenesis and elicits apoptosis, thereby countering tissue overgrowth. Unexpectedly, HSF1 physically neutralizes soluble amyloid oligomers (AOs). Beyond impeding amyloidogenesis, HSF1 shields HSP60 from direct assault by AOs, averting HSP60 destabilization, collapse of the mitochondrial proteome, and, ultimately, mitophagy and apoptosis. The very same mechanism occurs in Alzheimer’s disease. These findings suggest that amyloidogenesis may be a checkpoint mechanism that constrains uncontrolled growth and safeguards tissue homeostasis, congruent with its emerging tumor-suppressive function. HSF1, by acting as an anti-amyloid factor, promotes overgrowth syndromes and cancer but may suppress neurodegenerative disorders.

Overgrowth Syndromes—Evaluation, Diagnosis, and Management

Abnormally excessive growth results from perturbation of a complex interplay of genetic, epigenetic, and hormonal factors that orchestrate human growth. Overgrowth syndromes generally present with inherent health concerns and, in some instances, an increased risk of tumor predisposition that necessitate prompt diagnosis and appropriate referral. In this review, we introduce some of the more common overgrowth syndromes, along with their molecular mechanisms, diagnostics, and medical complications for improved recognition and management of patients affected with these disorders.