To provide a comprehensive bibliometric and visualized analysis of global macrodactyly research from 2005 to 2025, identify publication trends, leading contributors, research hotspots, and emerging directions in this rare congenital disorder. Publications from January 1,2005 to November 31,2025 were retrieved from the Web of Science Core Collection. English-language articles and reviews were included using the search terms "macrodactyly," "megalodactyly," "digital gigantism," and "giant digit." After removing duplicates, retracted items, and non-relevant records, eligible studies were analyzed. Microsoft Excel, VOSviewer, and CiteSpace were used to evaluate publication trends, geographic distribution, collaboration networks, and keyword co-occurrence patterns. A total of 162 publications met the inclusion criteria. Annual output increased steadily, with peaks in 2014 and 2020, and a strong upward cumulative trend (R2 = 0.9933). Research was mainly concentrated in the USA, China, and Europe, with limited intercontinental collaboration. Author and institutional analyses revealed several distinct collaboration clusters. Keyword co-occurrence and temporal mapping demonstrated a shift from early clinical and surgical topics toward molecular and genetic research, particularly involving PIK3CA-related mechanisms. Macrodactyly research has expanded over the past 2 decades, evolving from clinical descriptions to mechanistic studies driven by advances in molecular genetics. The identification of PIK3CA mutations has reshaped the field and introduced opportunities for targeted therapy. Despite increasing output, international collaboration remains limited. Future work should focus on multicenter studies, precision medicine approaches, and the development of evidence-based treatment strategies.

Isolated congenital muscular pseudohypertrophy of the upper limb is a very rare anomaly. With our case series spanning twenty years, we aim to illustrate the pathological anatomy associated with this rare disorder and present a surgical framework in the operative treatment of this elusive condition. Patients presenting at two institutions were retrospectively reviewed. Exclusion criteria include syndromes (e.g. CLOVES) or isolated macrodactyly. Patients who presented with worsening deformities such as increasing metacarpophalangeal joint ulnar deviation, hyperabduction of thumb with widening of webspace affecting grasp or wrist deformities were recommended surgery. Surgical procedures include removal of aberrant muscles, rebalancing procedures or osteotomies. A total of 25 patients were reviewed, of which 18 underwent surgery and 13 attended postoperative review. The median age was 7.5 years, and mean follow-up period was 42 months. Radial abduction improved from 54° to 36°, and ulnar deviation improved from 39° to 13°. All patients regained postoperative thumb opposition to the little finger, a function that had been previously lost. However, only 8/13 could oppose the thumb to the index finger postoperatively. Surgical findings revealed interesting additional layers of muscles which are unnamed, with some of these accounting for the deformities and others for bulk. The predominant finding was that of extra muscles rather than hypertrophied muscles. This is one of the largest reported series of congenital muscular pseudohypertrophy of the upper limb. We developed a scoring system for severity and an accompanying algorithm to guide when to offer surgery for moderate or severe deformities. These new muscle morphologies may shed light on evolutionary developmental biology pathways, allowing their safe removal during surgery.Level of evidence: IV.

Macrodactyly of the hand is an uncommon anomaly. There are few studies looking at late presentation or adults with macrodactyly. This study specifically aims to describe the presentation and surgical management of adult macrodactyly and to compare these findings with those in children, highlighting the distinct challenges associated with late presentation. This is a retrospective study of 13 adults (18 years or older) and 19 children with macrodactyly of the upper limb who underwent surgery in a 13 year period. Clinical features including radiographic findings, number and types of surgeries were compared between adults and children. Common reasons for presentation in adulthood were carpal tunnel syndrome and functional impairment. Radiographs of adults showed exostoses, arthritis, bony fusions and angulation deformities. The mean number of surgeries that children underwent was almost double that of adults. The average number of debulking procedures per patient was significantly more in children including soft tissue resection, osteotomy and reconstructive surgeries. Amputations were slightly more common in adults. Carpal tunnel syndrome or trigger fingers were seen only in adults. Adults and paediatric patients with macrodactyly seek treatment for different reasons. Presentation in childhood often results in multiple debulking stages or reconstructive attempts. In adults, surgery is often for improving function and usually single staged. Untreated, long-term progression of joint changes can lead to pain and disability. Recognition of these symptoms can guide treatment in older patients or prevent age-related changes in younger populations. IV.

Excessive proliferation and lipid accumulation of adipose tissue are the main pathological alterations in macrodactyly. Our previous studies found that macrodactyly exhibits abnormal lipid metabolism and inhibited autophagy, but the underlying mechanisms remain unclear. This study aims to investigate the regulatory mechanisms of autophagy in macrodactyly. The therapeutic impact and underlying mechanisms of autophagy on lipid accumulation, induced by a gain-of-function mutation of PIK3CA in macrodactyly, were assessed with respect to autophagy, lipid metabolism, oxidative stress, and deubiquitination. Autophagy deficiency resulting from PIK3CA mutation in macrodactyly led to excessive accumulation of adipose tissue. Lipid accumulation can be mitigated by inducing lipophagy of lipid droplets (LDs) in adipose derived stem cells of macrodactyly (Mac-ADSCs). The subsequent increase in free fatty acids (FFA) led to mitochondrial oxidative stress in Mac-ADSCs. Inducing autophagy exacerbated mitochondrial oxidative stress in Mac-ADSCs, thereby contributing to apoptosis. Additionally, the ablation of the deubiquitinase USP15 facilitated the degradation of LDs in Mac-ADSCs, through ubiquitin-dependent macrolipophagy. USP15 inhibitor reduced lipid accumulation in macrodactyly adipose tissue xenografts. In conclusion, activating PIK3CA mutation promotes excessive proliferation and lipid accumulation of Mac-ADSCs by inhibiting lipophagy. Targeted inhibition of USP15 may serve as a promising therapeutic approach for treating macrodactyly. A schematic illustrates that activating PIK3CA mutation promotes overgrowth of adipose tissue via inhibiting lipophagy in macrodactyly.

To conduct a visualization analysis of macrodactyly research from 2005 to 2024, providing a comprehensive overview of research trends, key contributors, and emerging topics. A visual analysis of macrodactyly related publications from 2005 to 2024 was conducted using the Web of Science Core Collection database. Publication trends, country and institutional contributions, author collaboration networks, and keyword co-occurrences were analyzed. Statistical analysis and visualization were performed using Microsoft Excel, R, VOSviewer, and CiteSpace. One hundred and fifty-three publications were included. Annual publication trends showed fluctuations but an overall growth in interest over time, with notable growth from 2011 to 2014 peaking at 15 publications in 2014. The United States led with 128 publications, followed by China (60), Italy (40), Japan (36), and Turkey (27), with prominent institutions such as Mayo Clinic and Harvard University playing pivotal roles. Key authors like Dr. Marybeth Ezaki, working with the team at Texas Scottish Rite Hospital for Children, made substantial contributions to establishing diagnostic frameworks. Most importantly, keyword analysis revealed a fundamental shift in research focus from clinical and surgical themes (represented by keywords such as "foot," "hand," and "osteotomy" in early periods) to molecular and genetic investigations (characterized by "PIK3CA," "activating mutations," and "overgrowth" in recent years). The strongest citation burst was "overgrowth" (2016-2020), followed by genetic-related terms, with "activating mutations" representing the most recent trend (2020-2024), indicating increasing emphasis on PIK3CA mutations as the current research hotspot. This study highlights the evolution of macrodactyly research and reveals fluctuating publication trends and substantial contributions from key countries, authors, and institutions. The transition from clinical and surgical approaches to molecular and genetic investigations underscores advancements in the field. Future research should prioritize integrating genetic findings with clinical applications and advancing diagnostics and treatment strategies.