Bannayan-Riley-Ruvalcaba Syndrome (BRRS) is a rare genetic disorder caused by germline mutations in the phosphatase and tensin homolog (PTEN) gene, leading to overgrowth and classified under PTEN hamartoma tumor syndrome (PHTS). It manifests with systemic features, including cutaneous, neurodevelopmental, and skeletal abnormalities, and is strongly associated with cancer risk. A literature review was conducted using PubMed and Web of Science databases up to April 2025, focusing on BRRS etiology, clinical features, diagnosis, and management. Most BRRS cases involve germline PTEN mutations, though some patients lack them. Clinical manifestations vary, with macrocephaly, lentiginous genital macules, intestinal polyps, and vascular anomalies being most common. Diagnosis is difficult due to the absence of standardized criteria; therefore, phenotypic assessment, molecular testing, imaging, and age-based considerations are essential. Management requires a multidisciplinary approach aimed at symptom control, early detection of malignancy, and family screening. Early recognition of BRRS features, along with prompt referral and intervention, can significantly improve outcomes. The lack of diagnostic guidelines and limited treatment options highlights the need for further research to establish standardized diagnostic and therapeutic strategies. The PTEN hamartoma tumor syndrome (PHTS) includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), PTEN-related Proteus syndrome (PS), and PTEN-related Proteus-like syndrome. CS is a multiple hamartoma syndrome with a high risk for benign and malignant tumors of the thyroid, breast, kidney, and endometrium. Affected individuals usually have macrocephaly, trichilemmomas, and papillomatous papules, and present by the late 20s. The lifetime risk of developing breast cancer is 85%, with an average age of diagnosis between 38 and 46 years. The lifetime risk for thyroid cancer (usually follicular, rarely papillary, but never medullary thyroid cancer) is approximately 35%. The lifetime risk for renal cell cancer (predominantly of papillary histology) is 34%. The risk for endometrial cancer may approach 28%. BRRS is a congenital disorder characterized by macrocephaly, intestinal hamartomatous polyposis, lipomas, and pigmented macules of the glans penis. PS is a complex, highly variable disorder involving congenital malformations and hamartomatous overgrowth of multiple tissues, as well as connective tissue nevi, epidermal nevi, and hyperostoses. Proteus-like syndrome is undefined but refers to individuals with significant clinical features of PS who do not meet the diagnostic criteria for PS. The diagnosis of PHTS is established in a proband by identification of a heterozygous germline PTEN pathogenic variant on molecular genetic testing. Treatment of manifestations: Treatment for the benign and malignant manifestations of PHTS is the same as for their sporadic counterparts. Topical agents (e.g., 5-fluorouracil), curettage, cryosurgery, or laser ablation may alleviate the mucocutaneous manifestations of CS but are rarely utilized; cutaneous lesions should be excised only if malignancy is suspected or symptoms (e.g., pain, deformity, increased scarring) are significant. Surveillance: To detect tumors at the earliest, most treatable stages: Children (age <18 years). Yearly thyroid ultrasound from the time of diagnosis (earliest reported at age 7 years) and skin check with physical examination. Adults. Yearly thyroid ultrasound and dermatologic evaluation. Women beginning at age 30 years. Monthly breast self-examination; annual breast screening (at minimum mammogram; MRI may also be incorporated). Starting by age 35 years, consider transvaginal ultrasound or endometrial biopsy. Men and women. Colonoscopy beginning at age 35 years with frequency dependent on degree of polyposis identified or family history of early-onset colon cancer (before age 40); biennial (every 2 years) renal imaging (CT or MRI preferred) beginning at age 40 years. Those with a family history of a particular cancer type at an early age. Consider initiating screening 5 to 10 years prior to the youngest age of diagnosis in the family. Evaluation of relatives at risk: When a PTEN pathogenic variant has been identified in a proband, molecular genetic testing of asymptomatic at-risk relatives can identify those who have the family-specific pathogenic variant and warrant ongoing surveillance. PHTS is inherited in an autosomal dominant manner. Because CS is likely underdiagnosed, the actual proportion of simplex cases (defined as individuals with no obvious family history) and familial cases (defined as ≥2 related affected individuals) cannot be determined. The majority of CS cases are simplex. Perhaps 10%-50% of individuals with CS have an affected parent. Each child of an affected individual has a 50% chance of inheriting the pathogenic variant and developing PHTS. Once a PTEN pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk is possible.

Phosphatase and tensin homolog (PTEN) hamartomas comprise a spectrum of disorders that involve multiple systems and originate from a group of allelic disorders from germ line mutations in the PTEN gene. PTEN hamartomas involve a spectrum of disorders with diversed clinical manifestations and diagnosis can be challenging, particularly when lesions mimic other conditions. We present a case of a PTEN hamartoma in an eighteen-year-old male, who presented with a history of swelling on the chin with episodic bleeds. Initial diagnosis of an arteriovenous malformation was made radiologically but was later confirmed by histopathological and immunohistochemistry to be a case of PTEN hamartoma. PTEN is a tumor suppressor gene, and patients with germline PTEN mutations are more likely to develop malignancies, particularly epithelial, mesenchymal, and hematopoietic cancers. PTEN hamartomas cause a variety of conditions, including Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, PTEN-related Proteus syndrome, and Proteus-like syndrome. As a result, cancer surveillance is critical in managing PTEN hamartoma tumor syndrome (PTHS) patients. All PTEN mutation carriers should adhere to approved cancer surveillance measures. This case highlights the unusual presentation of PTHS. It can present as an isolated PTEN hamartoma of Soft Tissue (PHOST) lesion without systemic findings and establishing a genetic diagnosis is important to the patient's future health. A multidisciplinary approach with the clinical, radiologic and pathologic findings of PTHS and PHOST lesions will more rapidly lead to an accurate diagnosis. Prompt diagnosis and appropriate treatment are important to prevent potentially severe outcomes.

The phosphatase and tensin homolog hamartoma tumor syndrome (PHTS) refers to a spectrum of disorders caused by variants of the phosphatase and tensin homolog (PTEN) gene, including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome, adult Lhermitte-Duclos disease, and autism spectrum disorders associated with macrocephaly. PHTS is characterized by hamartomas in multiple organs and is associated with an increased risk of developing malignant tumors including, breast, thyroid, endometrial, colorectal, and kidney tumors. Breast cancer is the most common malignancy associated with PHTS. We describe the case of a 44-year-old female patient with invasive ductal carcinoma of the right breast. Cobblestone papillomatosis was present in the gingiva. She had a medical history of bilateral adenomatous goiters for 10 years. Her mother had been diagnosed with breast cancer, thyroid and tongue tumors, gastric polyps, hepatic hemangioma, and collagen disease. Additionally, the patient's maternal grandmother had a history of colon cancer. Based on the patient's family history and physical findings, CS was suspected, and direct DNA sequencing analysis revealed a haplotype c.634del mutation in exon 7 of the PTEN gene. Although there is no clear evidence supporting risk-reducing surgery for PHTS, a right nipple-sparing mastectomy, sentinel lymph node biopsy, and tissue expander reconstruction were performed. We report a case of breast cancer with a newly diagnosed c.634del mutation in the PTEN gene. We also reviewed the current literature on PTEN genetic variants and breast cancer subtypes.

Excessive growth syndromes are a heterogeneous group of rare congenital disorders characterized by increased body size from the neonatal period or early childhood. In addition to accelerated growth, these conditions frequently co-occur with dysmorphic features and other medical problems, including intellectual disability, organ defects, and an increased risk of cancer. The objective of this study is to present a comprehensive overview of selected dysmorphic syndromes associated with excessive growth, with particular emphasis on syndromes with confirmed or strongly suspected monogenic etiology. The following aspects are discussed in this text: the pathogenesis of the condition, its inheritance, the characteristic clinical symptoms, the diagnostic approach, and the potential treatment options. A comprehensive analysis of data pertaining to syndromes of excessive growth, accompanied by either a recognized or postulated monogenic basis, was conducted based on scientific literature. A particular emphasis was placed on the examination of endocrinological, oncological, and prognostic aspects. The usefulness of genetic testing in the diagnostic process was also evaluated. A number of excessive growth syndromes were identified, including Sotos syndrome, Beckwith-Wiedemann syndrome, Simpson-Golabi-Behmel syndrome, Bannayan-Riley-Ruvalcaba syndrome, Marshall-Smith syndrome, Weaver syndrome, Nevo syndrome, and Elejalde syndrome. Clinical symptoms, prevalence of endocrine disorders, and risk of developing cancer were meticulously documented. Following a thorough analysis, a set of diagnostic schemes and indications for monitoring selected complications were proposed. The diagnosis of overgrowth syndromes is a complex process that requires a meticulous clinical evaluation and the application of contemporary genetic methodologies. Early identification of characteristic phenotypic and molecular features facilitates prompt implementation of appropriate treatment and monitoring of complications. The adaptation of therapeutic strategies to a specific syndrome and patient is pivotal to improving prognosis. Zespoły nadmiernego wzrostu to heterogenna grupa rzadkich wad wrodzonych, charakteryzujących się zwiększoną wielkością ciała już od okresu noworodkowego lub wczesnego dzieciństwa. Oprócz przyspieszonego wzrostu, często współwystępują z cechami dysmorfii oraz innymi problemami medycznymi, takimi jak niepełnosprawność intelektualna, wady narządowe czy zwiększone ryzyko rozwoju nowotworów. Celem niniejszej pracy jest przedstawienie przeglądu wybranych zespołów dysmorficznych związanych z nadmiernym wzrostem, ze szczególnym uwzględnieniem zespołów o potwierdzonej lub silnie podejrzewanej etiologii monogenowej. Omówiono ich patogenezę, dziedziczenie, charakterystyczne objawy kliniczne, podejście diagnostyczne oraz potencjalne możliwości leczenia. Analizie poddano dostępne w literaturze naukowej dane dotyczące zespołów nadmiernego wzrostu o znanym lub postulowanym podłożu jednogenowym. Szczególną uwagę poświęcono aspektom endokrynologicznym, onkologicznym i rokowniczym. Oceniono również przydatność badań genetycznych w procesie diagnostycznym. Zidentyfikowano szereg zespołów nadmiernego wzrostu, takich jak: zespół Sotos, Beckwitha-Wiedemanna, Simpsona-Golabiego-Behmela, Bannayana-Rileya-Ruvalcaby, Marshalla-Smitha, Weavera, Nevo oraz Elejalde. W każdym z nich opisano charakterystyczne objawy kliniczne, częstość występowania zaburzeń endokrynologicznych oraz ryzyko rozwoju nowotworów. Na podstawie analizy zaproponowano schematy diagnostyczne i wskazania do monitorowania wybranych powikłań. Rozpoznanie zespołów nadmiernego wzrostu wymaga uważnej oceny klinicznej oraz zastosowania nowoczesnych metod genetycznych. Wczesna identyfikacja charakterystycznych cech fenotypowych i molekularnych umożliwia szybsze wdrożenie odpowiedniego leczenia i monitorowania powikłań. Indywidualizacja opieki, w tym dostosowanie strategii terapeutycznych do konkretnego zespołu i pacjenta, jest kluczowa dla poprawy rokowania.