Macrodactyly (megalodactyly or digital gigantism) is a rare condition of overgrowth affecting one or more fingers or toes. We report a case of a 16-year-old Caucasian male with macrodactyly, lipomas, nevi, dysmorphic features, and autism. The clinical suspicion for a Proteus-like syndrome was high. Targeted PIK3CA, AKT1, and PTEN sequencing for the affected tissue was negative. Subsequent genetic testing revealed a 16p11.2 duplication along with a heterozygous pathogenic variant in PRRT2 (not causally associated with digit malformation). The clinical management of syndromic macrodactyly is well described by consensus guidelines, but isolated macrodactyly also needs pediatricians' attention and warrants a multidisciplinary approach. After reviewing the literature, a diagnostic algorithm for the approach and differential diagnosis of macrodactyly is provided. Phenotypes associated with PI3K/AKT/mTOR pathway mutations (including PIK3CA-related overgrowth spectrum PROS) are described. Late effects, follow-up schedules, and surveillance for cancer are discussed.

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.

PTEN Hamartoma Tumour Syndrome (PHTS) encompasses diverse clinical phenotypes, including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), Proteus syndrome (PS), and Proteus-like syndrome. This autosomal dominant genetic predisposition with high penetrance arises from heterozygous germline variants in the PTEN tumour suppressor gene, leading to dysregulation of the PI3K/AKT/mTOR signalling pathway, which promotes the overgrowth of multiple and heterogenous tissue types. Clinical presentations of CS range from benign and malignant disorders, affecting nearly every system within the human body. CS is the most diagnosed syndrome among the PHTS group, notwithstanding its weak incidence (1:200,000), for which it is considered rare, and its precise incidence remains unknown among other important factors. The literature is notably inconsistent in reporting the frequencies and occurrences of these disorders, adding an element of bias and uncertainty when looking back at the available research. In this review, we aimed to highlight the significant disparities found in various studies concerning CS and to review the clinical manifestations encountered in CS patients. Furthermore, we intended to emphasize the great significance of early diagnosis as patients will benefit from a longer lifespan while being unceasingly advised and supported by a multidisciplinary team.

PTEN hamartoma tumor syndrome (PHTS) is an umbrella term including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), PTEN-related Proteus syndrome (PS), and PTEN-related Proteus-like syndrome. One of the disorders in PHTS spectrum, CS is characterized by macrocephaly, mucocutaneous findings, gastrointestinal system (GIS) polyposis and an increased lifetime risk of GIS, breast, thyroid and other cancers. In this study, we report an adolescent patient presenting with recurrent life-threatening upper GIS bleeding as a result of hamartomatous polyposis. Genetic studies revealed a known pathogenic nonsense mutation confirming the initial diagnosis of CS. Additionally, we describe our therapeutic intervention to improve the patient`s clinical symptoms with sirolimus, which its use is infrequently addressed in the literature for pediatric age group harboring PTEN mutations.

The phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a collection of diseases stemming from mutations in the PTEN tumor suppressor gene and is characterized by variable expressivity and abnormal overgrowth in multiple body systems. Its clinical manifestations include, but are not limited to, lipomas, limb overgrowth, dermatologic lesions, and malignancy. The infrequency of occurrence and broadness of clinical presentation has made the diagnosis and differentiation of different subtypes of PHTS challenging. This case report describes a five-year-old patient with a history of autism and macrocephaly who presented to the emergency department with right lower quadrant (RLQ) pain concerning for appendicitis. A physical exam was significant for right leg hemihypertrophy. Imaging ruled out appendicitis but diagnosed two large right-sided abdominal lipomas. The patient was discharged with the recommendation to pursue genetic testing given the physical exam findings and history. Following confirmation of a PTEN tumor suppressor gene mutation, the patient continued to have increased frequency of abdominal pain, developed vision changes, and was diagnosed with a benign follicular thyroid nodule. Hemihypertrophy, recurrent unilateral lipomas, and a confirmed PTEN mutation are consistent with a diagnosis of Proteus-like syndrome, a rare subtype of PHTS.