Authors: Siham Nasri, Asmae Oulad Amer, Narjisse Aichouni...

Real macrodactylia is a rare congenital abnormality of unknown etiology, characterized by excessive growth of the anatomical structures of one or several rays of the hand. It is usually isolated and causes a fibrofatty infiltration mainly involving the palm. It can be caused by embryonic or neurogenic abnormalities with or without nerve involvement according to whether macrodactylia has led to an increase in the volume of a major nerve, more often the median. From an evolutionary point of view, it is necessary to distinguish between static macrodactylia (present at birth and remaining stable during growth) and progressive macrodactylia (with a disproportionate growths). Some other syndromes, tumors or abnormalities can cause an increase in finger volume. This abnormality results in functional disability but also in disfigurement. Treatment is based on surgery and rehabilitation.

Topics: Female; Fingers; Hand; Humans; Infant; Limb Deformities, Congenital

PubMed: 31007808
DOI: 10.11604/pamj.2018.31.61.15303

Authors: E C Warner

PubMed: 19989474
DOI: No ID Found

Authors: Jingheng Wu, Guanglei Tian, Yuan Ji...

PURPOSE

Macrodactyly is a rare, nonhereditary congenital deformity. Digital enlargement in macrodactyly involves all tissue types and presents alone or as part of a congenital deformity syndromes. Macrodactyly treatment largely depends on surgeons' experience and knowledge. Because there is a paucity of large cohort studies of macrodactyly in the literature, our goal was to retrospectively analyze macrodactyly cases in order to define a better system for diagnosis, classification, and prognosis.

METHODS

Medical records of 90 Chinese macrodactyly patients, including demographic characteristics, clinical presentations, anatomical distributions, x-rays, pathological findings, and treatments, were reviewed. Genetic analyses of 12 patients were also reviewed.

RESULTS

Disease incidence was similar across sex and geographical regions. Multiple-digit involvement was 2.6 times more frequent than single-digit involvement. The index finger, middle finger, and thumb were most commonly involved. Two digits were affected more often than 3, with the affected digits adjacent in most cases. The affected digit was in the median nerve innervation distribution in 79% of cases and was accompanied by enlargement and fat infiltration of the median nerve. Seven cases had syndactyly. Ten of the 12 cases subjected to PIK3CA mutation analysis were positive.

CONCLUSIONS

Macrodactyly represents a heterogeneous group of conditions, without significant sex or geographical predilection, which is usually present at birth. A high PIK3CA mutation-positive rate in affected tissues suggests a similar cellular mechanism for overgrowth in patients with various clinical presentations.

TYPE OF STUDY/LEVEL OF EVIDENCE

Prognostic IV.

Topics: Fingers; Humans; Infant, Newborn; Limb Deformities, Congenital; Retrospective Studies; Syndactyly

PubMed: 32299688
DOI: 10.1016/j.jhsa.2020.03.002

Work-Up and Treatment Strategies for Individuals with -Related Disorders: A Consensus of Experts from the Scientific Committee of the Italian Macrodactyly and PROS Association.

Authors: Andrea Gazzin, Chiara Leoni, Germana Viscogliosi...

-related disorders encompass many rare and ultra-rare conditions caused by somatic genetic variants that hyperactivate the PI3K-AKT-mTOR signaling pathway, which is essential for cell cycle control. -related disorders include -related overgrowth spectrum (PROS), -related vascular malformations and -related non-vascular lesions. Phenotypes are extremely heterogeneous and overlapping. Therefore, diagnosis and management frequently involve various health specialists. Given the rarity of these disorders and the limited number of centers offering optimal care, the Scientific Committee of the Italian Macrodactyly and PROS Association has proposed a revision of the most recent recommendations for the diagnosis, molecular testing, clinical management, follow-up, and treatment strategies. These recommendations give insight on molecular diagnosis, eligible samples, preferable sequencing, and validation methods and management of negative results. The purpose of this paper is to promote collaboration between health care centers and clinicians with a joint shared approach. Finally, we suggest the direction of present and future research studies, including new systemic target therapies, which are currently under evaluation in several clinical trials, such as specific inhibitors that can be employed to downregulate the signaling pathway.

Topics: Limb Deformities, Congenital; Italy; Mutation; Fingers; Humans; Consensus; Phosphatidylinositol 3-Kinases; Class I Phosphatidylinositol 3-Kinases

PubMed: 38136956
DOI: 10.3390/genes14122134

Authors: Mouna Ejjiyar, Saloua Ettalbi

Macrodactylia is a rare congenital malformation of unknown origin that can affect the fingers or the toes. It is characterized by an increase in the size of all the elements of one or more rays, recognizable at birth or occurring in a progressive manner. Social, aesthetic as well as functional impact imposes early surgical management or even amputations in advanced forms. We report the case of a 18-year old unmarried, left handed patient without a profession, admitted to the Department of Burns, Plastic and Aesthetic Surgery at the University Hospital Mohammed VI in Marrakech, with progressive acrodactylia involving the first and the second ray of the right hand. Clinical examination showed hypertrophy of the first two rays of the right hand associated with predominant fibro-fatty infiltration of the palmar as well as phalanx deviation 90 degrees at the level of the second finger. Given the severity of the macrodactylia, amputation of the second ray associated with reduction of the fatty infiltration of the palmar was proposed to the patient, allowing him to maintain pollici-digital pinch and to return to a social life as close as possible to normal life.

Topics: Adolescent; Amputation, Surgical; Fingers; Humans; Limb Deformities, Congenital; Male; Severity of Illness Index

PubMed: 30197736
DOI: 10.11604/pamj.2018.30.45.15118

Review

Authors: Gozde Akgumus, Fengqi Chang, Marilyn M Li...

Somatic variants have been well described in tumorigenesis; however, they are only recently appreciated in other human disorders, such as mosaic overgrowth syndromes. Although overgrowth is a manifestation in many genetic syndromes, not all overgrowth syndromes are inherited. Mosaic somatic variants have been lately described in several overgrowth disorders, such as Proteus syndrome, CLOVES (congenital, lipomatous, overgrowth, vascular malformations, epidermal nevi, and spinal/skeletal anomalies and/or scoliosis) syndrome, and megalencephalyepolymicrogyria-polydactyly-hydrocephalus syndrome. These syndromes are caused by somatic variants in the genes associated with the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway, resulting in a spectrum of overgrowth syndromes with overlapping features that could be difficult to distinguish based on phenotypic presentations alone. In addition, Sanger sequencing is ineffective for the detection of a causal variant because of the mosaic nature of these variants, whereas targeted next-generation sequencing technology offers a deeper sequencing coverage and allows the detection of low-level mosaicism. Recent studies have shown that the causal variants are only present in the affected tissues in most cases, and can be enriched by in vitro tissue culture. In this review, we describe several mosaic somatic overgrowth syndromes caused by variants in genes of the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway, their phenotypic and molecular spectrum, and the clinical utility of next-generation sequencing technology in the diagnosis of these disorders.

Topics: Animals; Clinical Trials as Topic; Female; Fingers; Genetic Testing; Genetic Variation; High-Throughput Nucleotide Sequencing; Humans; Hydrocephalus; Hypoglycemia; Limb Deformities, Congenital; Lipoma; Malformations of Cortical Development; Mosaicism; Musculoskeletal Abnormalities; Nevus; Phosphatidylinositol 3-Kinase; Polydactyly; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases; Vascular Malformations

PubMed: 28502730
DOI: 10.1016/j.jmoldx.2017.04.001

Authors: Lu Chen, Wei Huang, Wei Chen...

The purpose of the study was to produce an algorithm and surgical procedure for optimum treatment of pedal macrodactyly. Surgery was performed on 27 feet of 26 patients with a mean age of 33 months at the time of surgery (range: 7-108 months). A multi-technique procedure based on the involved elements of the foot (soft tissue, phalanx, or metatarsal, or a combination of these) was adopted. The intermetatarsal width ratio, phalanx spread angle, and metatarsal spread angle was used to evaluate the severity of the macrodactyly and the effect of treatment. The Oxford Ankle Foot Questionnaire for Children and the Questionnaire for Foot Macrodactyly were employed to evaluate the clinical results. Under the guidelines of the treatment algorithm, all patients were successfully operated on using the multi-technique procedure; the sizes of the affected feet decreased significantly. After a mean of 33 months (range: 18-42 months) follow-up, the intermetatarsal width ratio decreased from 1.13 to 0.93 ( < 0.05), the phalanx spread angle decreased from 31.3° to 17.9° ( < 0.05), the metatarsal spread angle decreased from 33.2° to 15.8° ( < 0.05), and the mean score for the Oxford Ankle Foot Questionnaire for Children improved from 42 to 47 ( < 0.05) after surgery. The mean score for the Questionnaire for Foot Macrodactyly was 9.35 at the time of follow-up. The goal of the treatment of pedal macrodactyly is to obtain a functional and cosmetically acceptable foot. This treatment algorithm and multi-technique procedure could fully satisfy this goal.

Topics: Lower Extremity; Child; Limb Deformities, Congenital; Child, Preschool; Foot Deformities, Congenital; Fingers; Humans; Foot

PubMed: 36849126
DOI: 10.1080/2000656X.2021.2017293

Authors: Xi Yang, Yongkang Jiang, Gang Han...

Macrodactyly is a congenital disease characterized by aggressive overgrowth of adipose tissue in digits or limbs frequently accompanied with hyperostosis and nerve enlargement; its pathological mechanism is poorly understood. Adipose-derived stem cells (ASCs) have been extensively studied in tissue engineering and regenerative medicine as an ideal alternative substitute for bone marrow-derived mesenchymal stem cells (BM-MSCs), but their pathological role is largely unknown. In this study, ASCs from macrodactyly adipose tissues (Mac-ASCs) were isolated and compared to ASCs derived from the normal abdominal subcutaneous adipose tissue (Sat-ASCs) for cell morphology, surface marker expression, proliferation rate, and tri-lineage differentiation potential. Despite similar cell morphology and cell surface marker expression, Mac-ASCs showed higher cell proportion in the S phase and increased proliferation compared with Sat-ASCs. Moreover, osteogenic and chondrogenic differentiation capacities were enhanced in Mac-ASCs, with reduced adipogenic potential. In addition, the expression levels of adipogenic genes were lower in undifferentiated Mac-ASCs than in Sat-ASCs. These findings unraveled enhanced proliferation activity, a regression in the differentiation stage, and greater potentiality of ASCs in macrodactyly, which could contribute to hyperostosis and nerve enlargement in addition to adipose tissue overgrowth in patients.

Topics: Adipocytes; Adipogenesis; Adipose Tissue; Biomarkers; Cell Differentiation; Cell Proliferation; Fingers; Gene Expression Profiling; Gene Expression Regulation; Humans; Immunophenotyping; Limb Deformities, Congenital; Phenotype; Stem Cells

PubMed: 28894288
DOI: 10.1038/s41598-017-11666-3

Authors: Gregoire Rougereau, Franck Fitoussi, Thibault Marty-Diloy...

BACKGROUND

Amputation of the abnormal segment seems to be the reference standard treatment for the surgical management of macrodactyly of the foot in children. Our objectives here were to detail the surgical strategies according to the cause, anatomical characteristics, and static or progressive nature of the macrodactyly and to evaluate the long-term clinical outcomes.

HYPOTHESIS

Conservative treatment can be an option in the management of static macrodactyly of the foot in children.

MATERIAL AND METHODS

We retrospectively included 24 feet in 19 patients seen consecutively. There were 12 primary and 12 secondary types. The macrodactyly was static in 9 cases and progressive in 15 cases. The treatment consisted in either conservative procedures or amputation of the segment. All patients completed the Oxford Ankle Foot Questionnaire for Children (OxAFQ-C) to evaluate their quality of life, shoe wear issues, and satisfaction with their treatment.

RESULTS

Mean age at first surgery was 5.8 years (range, 0.5-11.5) and the mean interval between two procedures was 2.3 years (range, 0.3-5.5). Mean number of procedures per foot was 2.2 par pied (range, 0-7). All 9 static forms were managed conservatively. Amputation was performed in 11 of the 15 progressive forms. The mean number of procedures was significantly higher in the progressive forms (4.1 vs. 1.5/pied; p=0.006). Two patients died during follow-up. The remaining 17 patients, with 22 affected feet (primary and secondary in 11 cases; progressive in 14 cases and static in 8 cases) were re-evaluated. Mean follow-up was 9.4 years (range, 2.7-20.6). The final OxAFQ-C score was 46/60 (range, 18-58). Of the 17 patients, 86% would be willing to repeat the same surgical procedures and 77% were satisfied with their treatment at last follow-up. We found no differences between the groups managed with amputation and with conservative treatment regarding quality of life, satisfaction, or shoe size difference.

CONCLUSIONS

Conservative treatment deserves a place in the treatment of static macrodactyly of the foot in children. Regarding amputation of the segment in progressive forms, it is important to reassure the patients and parents about the expected results but also to inform them about the risk of requiring repeat surgical procedures.

LEVEL OF EVIDENCE

IV, retrospective study.

Topics: Humans; Child; Infant; Child, Preschool; Retrospective Studies; Quality of Life; Foot

PubMed: 34648998
DOI: 10.1016/j.otsr.2021.103109

Authors: J H Wu, G L Tian, M M Tian...

OBJECTIVE

To analyze the clinical characteristics of 170 cases of macrodactyly.

METHODS

Medical records of 170 macrodactyly patients at Beijing Jishuitan Hospital between March 2006 and October 2019, including demographic characteristics, clinical presentations, anatomical distributions, X-rays, pathological findings, and treatments, were reviewed. PIK3CA mutation analyses of 12 patients were also reviewed.

RESULTS

Disease incidence was similar across sex and geographical regions. Multiple-digit involvement was 3.9 times more frequent than single-digit involvement. In upper deformit: ies, the index finger, middle finger and thumb were mostly involved, and the second and third toes were the most affected on the foot. Two digits were affected more often than three digits, with the affected multiple digits were adjacent most time. The cases of progressive macrodactyly, in which the affected digits grew at a faster rate than the unaffected digits, were found more than static type. Most of progressive macrodactyly were noticed at birth. In terms of nerve involvement, affected fingers mostly occurred in the median nerve innervation area (79.4%) accompanied by median nerve and brunches enlargement and fat infiltration, i.e., nerve territory oriented; affected toes mostly occurred in the medial plantar nerve innervation area (89.1%), marked with overgrowth of adipose tissue with a lesser degree of neural overgrowth, i.e., lipomatous. Only 17 cases had comorbid of syndactyly. The metacarpal bones were involved only in progressive type of macrodactyly. Ten of the 12 cases subjected to mutation analysis were positive. Among all tested specimens, mutation levels ranged from 7% to 27%. In terms of tissue sources in which a mutation was found, adipose tissue had the highest mutation detection rate, followed by nerve and skin. All the DNA samples of blood from the 12 mutation-positive patients were negative.

CONCLUSION

Macrodactyly fingers mostly occurred in the median nerve innervation area accompanied by median nerve and brunches enlargement and fat infiltration. The index and middle fingers were mostly involved. Macrodactyly toes mostly occurred in the medial plantar nerve innervation area, marked with overgrowth of adipose tissue with a lesser degree of neural overgrowth. The second and third toes were the most affected on the foot. A high proportion (83%) of isolated macrodactyly patients carry activating PIK3CA mutations. Adipose, nerve, and skin tissues provide the highest PIK3CA mutation detection yield among all types of tissue studied.

Topics: DNA Mutational Analysis; Fingers; Humans; Infant, Newborn; Limb Deformities, Congenital; Mutation; Toes

PubMed: 34145866
DOI: 10.19723/j.issn.1671-167X.2021.03.025