Search

Macrodactyly is a rare congenital limb difference manifesting as an overgrowth of one or more fingers or toes. The pathological process affects all tissues of the ray in the hand or foot. The enlargement can significantly alter the limb's appearance and impair its function. The role of a pediatrician is to distinguish isolated macrodactyly from syndromic conditions (including PIK3CA-Related Overgrowth Spectrum) or mimicking conditions to enable early interdisciplinary consultation and treatment planning. The psychological stigma associated with this often disfiguring condition necessitates support for patients and their family. We present a practical guide for physicians who might be the first to raise suspicion of macrodactyly and initiate further diagnostics to achieve adequate treatment and support for children and caregivers. [ABSTRACT FROM AUTHOR]

Macrodactyly is a rare congenital limb difference manifesting as an overgrowth of one or more fingers or toes. The pathological process affects all tissues of the ray in the hand or foot. The enlargement can significantly alter the limb’s appearance and impair its function. The role of a pediatrician is to distinguish isolated macrodactyly from syndromic conditions (including PIK3CA-Related Overgrowth Spectrum) or mimicking conditions to enable early interdisciplinary consultation and treatment planning. The psychological stigma associated with this often disfiguring condition necessitates support for patients and their family. We present a practical guide for physicians who might be the first to raise suspicion of macrodactyly and initiate further diagnostics to achieve adequate treatment and support for children and caregivers.

PIK3CA-related overgrowth spectrum (PROS) is a heterogeneous group of diseases, with varied clinical presentations ranging from isolated segmental overgrowths to megalencephaly and vascular malformations, all resulting from post-zygotic activating mutations in PIK3CA. Isolated macrodactyly of upper limb is extremely rare, accounting only for 0.9%–1% of all congenital anomalies of the upper limb. This report describes a case of congenital, isolated, nonprogressive macrodactyly of the right index finger and thumb, in an adult patient that was treated with debulking surgery. The microscopic features were compatible with lipomatosis of nerve. Due to the prompt and pertinent molecular testing, which identified a somatic PIK3CA variant, c.3140A > G, p.H1047R., the case was classified as a PROS. The availability of mTOR inhibitors offers additional treatment possibilities in cases with progressive disease. This case report highlights the importance of molecular testing to identify PROS, to further the knowledge of this continually expanding entity. [ABSTRACT FROM AUTHOR]

Macrodystrophia lipomatosa is a rare form of nonhereditary congenital localized gigantism involving upper and lower limbs and is characterized by overgrowth of all the mesenchymal elements predominantly fibro-adipose component, in the distribution of a particular nerve, usually median nerve. It usually presents with progressive painless overgrowth of the involved limb, toe, or digit and is associated with macrodactyly. It might cause limitation of the movement of the involved part. Imaging has an important role in diagnosing this condition and differentiating it from malignant mimics. Imaging findings include hypertrophy of the mesenchymal elements of the involved digits and/or limbs predominantly fibro adipose component with associated overgrowth of the phalanges. In this case report, we present a case of unilateral involvement of index finger and thumb with associated macrodactyly.

Macrodactyly, a often congenital anomaly, entails abnormal enlargement of digits, predominantly affecting hands or feet, either in isolation or as part of a syndromic condition. The authors present a case of Macrodystrophia Lipomatosa (ML), a form of macrodactyly, in a 62-year-old patient, emphasizing macrodactyly manifestations through clinical and radiological assessments. Additionally, the authors explore anatomical aspects related to nerve distribution in affected digits, providing a comprehensive understanding of ML. Teaching Point: Explore macrodactyly, emphasizing digits nerve plexus anatomy, which can reveal crucial clues for diagnosing a specific form of this anomaly.

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 (p < 0.05), the phalanx spread angle decreased from 31.3° to 17.9° (p < 0.05), the metatarsal spread angle decreased from 33.2° to 15.8° (p < 0.05), and the mean score for the Oxford Ankle Foot Questionnaire for Children improved from 42 to 47 (p < 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. [ABSTRACT FROM AUTHOR]

Macrodystrophia Lipomatosa (MDL) of the toe is a rare, congenital, disproportionate overgrowth involving one or more digits in the lower limb. Despite being a benign condition, when left untreated, it may cause physical impairment and interfere with daily activities. This form of localised gigantism is the result of excessive proliferation of fibroadipose tissue within the nerve along with associated macrodactyly. The mainstay of treatment is debulking or amputation to accommodate the patient’s daily activities, as well as for cosmesis. In this case report, the clinical and radiographic findings, anatomical descriptions, and histopathological findings are presented. The difference between MDL, fibrolipomatous hamartoma (FLH) and lipomatosis of the nerve (LON) are also discussed.

Macrodactyly is a very rare congenital difference that affects hands and feet with significant developmental and psychological implications. Macrodactyly is attributed to a somatic mutation in PIK3CA, a component of the mTOR pathway-related overgrowth disorders. Other medical conditions have been associated with macrodactyly (e.g., neurofibromatosis and Proteus syndrome). A thorough investigation of the presence of these conditions should be undertaken by the multidisciplinary team. The aim of this study is to summarize the main clinical characteristics and associated conditions, with an emphasis on diagnosis and surgical treatment options. We present several clinical cases after a retrospective chart review of macrodactyly cases and a comprehensive literature review. The indications for surgery include peripheral compressive neuropathies (e.g., carpal tunnel syndrome), grotesque enlargement interfering with function, psychosocial distress due to the deformity, and macrodystrophic lipomatosis with proximal upper limb involvement. The main surgical treatment options are categorized as follows: digit reduction (e.g., soft tissue debulking, skeletal shortening/ terminalization, Barsky procedure, and Tsuge technique), limitation of growth (digital nerve stripping and epiphysiodesis), and correction of deviation (wedge or angulation osteotomy, arthrodesis, Millesi procedure for thumb macrodactyly correction, toe-to-hand transfer, ray resection, and combination of bony reduction and soft tissue debulking). Macrodactyly correction requires surgical experience and an individualized approach. Treatment is primarily surgical; however, efforts are being made to delineate the root cause of macrodactyly and provide nonoperative management. [ABSTRACT FROM AUTHOR]

Background: Somatic mosaicism for PIK3CA mutations causes various types of growth disorders, which have been summarized under the term PROS (PIK3CA related overgrowth spectrum). Targeted therapy with PI3K inhibitors seems to be a promising alternative for severe PROS cases. Therefore, PIK3CA testing may become more relevant in the future. Methods: We report on 14 PROS patients, who had surgery for macrodactyly in the majority of cases. Clinical data were retrieved from the patient's records. Macroscopic and microscopic findings were retrospectively reviewed. Mutational analysis was performed on formalin-fixed paraffin-embedded (FFPE) material. Results: Patient age ranged from 7 months to 35 years. Five patients showed additional anomalies. One patient had CLOVES syndrome. The majority of the specimens were ray resections characterized by hypertrophic fat tissue. Overall, microscopy was subtle. The abnormal adipose tissue showed lobules exhibiting at least focally fibrous septa. In each case, we could detect a PIK3CA mutation. Conclusion: Histology of affected fat tissue in PROS patients is overall nonspecific. Therefore, mutational analysis represents the key to the diagnosis, especially in unclear clinical cases. We demonstrated that FFPE material is suitable for PIK3CA testing, which can be considered as basis for targeted therapy with PI3K inhibitors. [ABSTRACT FROM AUTHOR]

Background: Macrodactyly is a rare congenital disorder of overgrowth affecting the digits of the upper or lower extremity. Mostly, patients are surgically treated during childhood to reduce the digit or to stop growth. There are no standardized guidelines for the treatment and follow-up of macrodactyly. Consequently, follow-up may not be regularly scheduled into adulthood. Methods: A retrospective, descriptive analysis of patients with the long-term progression of macrodactyly who presented at our tertiary referral hospital between July 2018 and March 2020 was performed. All patients from our local macrodactyly database were screened for progression of macrodactyly since adulthood; this resulted in four patients. The aim of these case series is to highlight the clinical features and disease course at long-term follow-up. Results: All patients were surgically treated during childhood and showed progression of tissue overgrowth during adult life. All patients developed severe secondary degenerative bone changes in macrodactyly affected digits, such as ankyloses of joints, new bone formation, and bony spurs. Subsequently, tissue overgrowth and degenerative bone changes led to functional problems. Conclusion: Patients with macrodactyly may experience growth during adult life, which may progress to deforming changes. Consequently, patients should be informed about the possible growth, and the progressive growth should be monitored.

Klippel–Trenaunay syndrome (KTS) is a congenital, uncommon but a well-recognized disorder, characterized by cutaneous hemangiomas, varicosities, and unilateral bone and soft tissue hypertrophy with different localization. Generally diagnosed at birth or first few years of life. KTS represents a syndrome of interest for those in the field of oral and maxillofacial radiology and pathology because of high incidence of variations seen in the orofacial region in affected patients. A case of a 3-year-old female patient with KTS reported to the Department of Pedodontics and Preventive Dentistry for extraction, and we have documented and tabulated the Orodental manifestation of this patient.

Jian-Feng Li,1 Guang-Lei Tian,2 Hui Pan,3 Wen-Tong Zhang,1 Da-Cun Li,1 Jing-Da Liu,1 Liang Zhao,1 Hai-Lei Li1 1Department of Hand Surgery, Beijing Shunyi District Hospital; Shunyi Teaching Hospital of Capital Medical University, Beijing, 101300, People’s Republic of China; 2Department of Hand Surgery, Beijing Jishuitan Hospital; Peking University Fourth School of Clinical Medicine, Beijing, 100035, People’s Republic of China; 3Department of Pathology, Beijing Shunyi District Hospital; Shunyi Teaching Hospital of Capital Medical University, Beijing, 101300, People’s Republic of ChinaCorrespondence: Jian-Feng LiDepartment of Hand Surgery, Beijing Shunyi District Hospital; Shunyi Teaching Hospital of Capital Medical University, No. 3 Guangming South Street, Shunyi District, Beijing, 101300, People’s Republic of China, Tel +86 10 69423220, Email drlijf27@126.comObjective: This study aimed to explore the pathogenic genes and mutation sites of macrodactyly.Methods: Whole-exome sequencing was performed on the pathological tissue and peripheral blood of 12 patients with macrodactyly who were operated in our hospital between June 2018 and May 2020. In order to conduct comprehensive bioinformatics analysis and screen the pathogenic genes of macrodactyly, the patients were divided into four groups: macrodactyly of finger group, macrodactyly of foot group, macrodactyly and syndactyly of finger group, and macrodactyly and syndactyly of foot group. The results of the whole-exome sequencing were verified using Sanger sequencing in order to clarify the pathogenic genes and mutation sites of macrodactyly, and immunohistochemical analysis of the protein signaling pathways encoded by the pathogenic genes was performed to observe the protein expression and further verify the mutant genes.Results: In the comprehensive bioinformatics analysis and Sanger verification of the whole-exome sequencing, the PIK3CA gene mutation was screened as the pathogenic gene of macrodactyly. The mutation sites were identified as the p.E542K (c.G1624A) and p.E545K (c.G1633A) sites of exon10 and the p.H1047R (c.A3140G) and p.G1049R (c.G3145C) sites of exon21. Among these, the p.G1049R (c.G3145C) locus was found in macrodactyly for the first time. The mutation of the PIK3CA gene was also found to lead to increased expression of serine-threonine kinase (AKT) in adipocytes in the PI3K-AKT-mTOR signaling pathway.Conclusion: Mutation of the PIK3CA gene leads to the enhancement of the PI3K-AKT-mTOR signaling pathway, which is the cause of macrodactyly. There is also some diversity in PIK3CA gene mutation sites.Keywords: hand deformity, foot deformity, macrodactyly, PIK3CA gene

Macrodactyly is a serious and rare disease and considered one of the most difficult pathologies to treat. There is no rule and the treatment for each patient must be tailor-made, depending on the location and degree of macrodactyly. Although amputation is a valid option for adult patients, nail preservation and reconstruction are important and has a direct impact on the treatment outcome, both aesthetically and on the patient's self-esteem. We have used a wide, z-shaped fingertip flap associated with the preservation of a nail quadrant, bone shortening and distal interphalangeal arthrodesis. We have obtained good functional and aesthetic outcomes with this 'quadrant flap' technique. The technique allows decreasing digit size and volume and reconstruction of the nail complex and finger pulp. Level of Evidence: Level V (Therapeutic) [ABSTRACT FROM AUTHOR]

Fibrolipomatous hamartoma is a rare benign congenital overgrowth of fibroadipose tissue in the nerve sheath. While usually affecting the median nerve, the digits of the hands and feet are sometimes affected and may result in macrodactyly, which is referred to as macrodystrophia lipomatosa. We present a rare case of fibrolipomatous hamartoma in a 6-week-old female's foot with macrodactyly and syndactyly and discuss its presentation and radiologic features.

Megadactyly of the foot is uncommon non hereditary congenital anomalies of the extremities and poses a dilemma on treatment however multiple treatment modalities were developed but is not uniform to all patients with megadactyly. The goal of the surgical treatment is to achieve painless and function of the foot. We report a 14 years old male presented with complaints of progressive enlargement 2nd, 3rd, 4th and 5th toes of the right foot since birth, associated with inability to wear shoes. One month prior to admission he experienced gradual onset painful forefoot and toes that was increasing in severity with time associated with inability to walk normally. He is the first born in a family of four children and his other siblings are healthy with no anomalies. On clinical evaluation, he was health with stable vitals, with enlarged 2nd, 3rd, 4th and 5th toes of the right foot with no tenderness with intact neurovascular status. On clinical and radiological evaluation he was diagnosed with congenital megadactyly of the right foot, a multidisciplinary team including orthopedic surgeons and prosthetics team agreed to do trans-metatarsal, then partial foot prosthesis fabrication. He underwent trans-metatarsal amputation of the affected foot and tissue sample was taken for histopathology. The histological findings revealed bone enlargement with increased proliferation of subcutaneous adipose tissues with increased fibrous septae together with thinning of the epidermis, features suggestive of lipomatosis. The wound site healed very well after 14 days stitches were removed and the child was scheduled for follow-up after six weeks, 12 weeks and 6 month post-surgery. On the last visit he was free from pain on his right forefoot and toes, able to wear fabricated partial foot prosthesis and shoes normally, walk with no incapacitation. Our case report is unique due to the involvement of the multiple toes of the right foot with syndactyly at third and fourth toes and its management is challenging because there is no uniformity in its surgical treatment, in our case trans-metatarsal amputation was done and the patient progressed well after six months of follow up. Foot megadactyly is uncommon congenital malformation, most common on the right foot. Regardless of the dilemma on treatment, the trans-metatarsal amputation and a fabricated prosthesis to our patient fulfilled the goals of painless right foot and able to wear shoes and walk normally with no impairment. • Megadactyly of the foot is uncommon non-hereditary congenital anomaly of the extremities. • We report a case of megadactyly involving multiple toes of the right foot with syndactyly at the third and fourth toes. • Surgical treatment is important, to alleviate pain, to achieve foot functioning and cosmetic purposes. [ABSTRACT FROM AUTHOR]

Neural fibrolipoma, also known as fibrolipomatous hamartoma (FLH), is a rare benign tumor that usually affects the upper limb and tends to develop near the n. median. FLH is a rare birth defect defined by the noncancerous growth of fibroadipose tissue around nerve bundles. These conditions are associated with abnormal bone growth, resulting in macrodactyly in about one-third of cases. The illness is medically referred to as macrodystrophia lipomatosa (MDL). A-4 years old girl presents with the index finger and thumb larger than the surrounding fingers and has been present since birth. Over time, the index finger and thumb continue to enlarge. This enlargement is accompanied by pain, a tingling sensation, and occasional bluish discoloration, especially at night. The patient is the third child out of four siblings, with a history of normal birth and no abnormalities in other parts of the body. The patient can grip objects in daily activities, but there is noticeable stiffness in the right hand. FLH with macrodactyly is an uncommon abnormality that can manifest as either a minor lesion or a big mass affecting the entire extremity. Clinically, it is challenging to challenging to diagnose FLH in patient with macrodactyly. It is crucial to possess a thorough understanding of the distinctive histology and radiological findings in order to accurately diagnose and treat the condition. • Neural fibrolipoma with macrodactyly is a rare condition • Diagnosing neural fibrolipoma in patients with macrodactyly is tough • Key histology and imaging insights are essential for accurate diagnosis and treatment [ABSTRACT FROM AUTHOR]

Context Natriuretic peptide receptor-C (NPR-C, encoded by NPR3) belongs to a family of cell membrane–integral proteins implicated in various physiological processes, including longitudinal bone growth. NPR-C acts as a clearance receptor of natriuretic peptides, including C-type natriuretic peptide (CNP), that stimulate the cGMP-forming guanylyl cyclase-coupled receptors NPR-A and NPR-B. Pathogenic variants in CNP , NPR2 , and NPR3 may cause a tall stature phenotype associated with macrodactyly of the halluces and epiphyseal dysplasia. Objective Here we report on a boy with 2 novel biallelic inactivating variants of NPR3. Methods History and clinical characteristics were collected. Biochemical indices of natriuretic peptide clearance and in vitro cellular localization of NPR-C were studied to investigate causality of the identified variants. Results We identified 2 novel compound heterozygous NPR3 variants c.943G>A p.(Ala315Thr) and c.1294A>T p.(Ile432Phe) in a boy with tall stature and macrodactyly of the halluces. In silico analysis indicated decreased stability of NPR-C, presumably resulting in increased degradation or trafficking defects. Compared to other patients with NPR-C loss-of-function, the phenotype seemed to be milder: pseudo-epiphyses in hands and feet were absent, biochemical features were less severe, and there was some co-localization of p.(Ile432Phe) NPR-C with the cell membrane, as opposed to complete cytoplasmic retention. Conclusion With this report on a boy with tall stature and macrodactyly of the halluces we further broaden the genotypic and phenotypic spectrum of NPR-C-related tall stature. [ABSTRACT FROM AUTHOR]

Isolated macrodactyly in adults caused by mosaic pattern PIK3CA mutation can result in significant functional impairment and psychological burden. Due to the rarity of this condition there are no clear treatment guidelines, and those few available are focused on paediatric cases. Reports on surgical management of isolated macrodactyly in adults are lacking. We present here the surgical management through partial amputation of enlarged rays of the right hand in an individual affected by low-grade mosaic PIK3CA mutation.

Abstract Background Isolated macrodactyly is a severe congenital hand anomaly with functional and physiological impact. Known causative genes include PIK3CA, AKT1 and PTEN. The aim of this study is to gain insights into the genetics basis of isolated macrodactyly. Results We enrolled 24 patients with isolated macrodactyly. Four of them were diagnosed with Proteus syndrome based on skin presentations characteristic to this disease. Targeted next-generation sequencing was performed using patients’ blood and affected tissues. Overall, 20 patients carry mosaic PIK3CA pathogenic variants, i.e. p.His1047Arg (N = 7), p.Glu542Lys (N = 6), p.Glu545Lys (N = 2), p.His1047Leu (N = 2), p.Glu453Lys (N = 1), p.Gln546Lys (N = 1) and p.His1047Tyr (N = 1). Four patients who met the diagnostic criteria of Proteus syndrome carry mosaic AKT1 p.Glu17Lys variant. Variant allele frequencies of these mosaic variants obtained through next-generation sequencing range from 10 to 33%. In genotype–phenotype correlation analysis of patients with PIK3CA variant, we found that patients with the macrodactyly of the lower limbs tend to carry PIK3CA variants located in the helical domain (P = 0.005). Conclusions Mosaic PIK3CA and AKT1 variants can be found in all of our samples with isolated macrodactyly. Insights into phenotypic and genetic spectrum of isolated macrodactyly may be helpful in perusing a more precise and effective management of isolated macrodactyly.

This case report presents a lipofibromatous hamartoma of the median nerve in a 31-year-old man who presents local deformity and a sensory deficit in the nerve territory. The tumor was evaluated with magnetic resonance, computed tomography, and plain film radiography, studying the pathognomonic findings of this tumor. The patient did not want surgical treatment because of prior surgical sequelae. A prior surgical biopsy was reported as a peripheral nerve with normal axonal fascicles surrounded by abundant fibroadipose tissue. This tumor has a low incidence with less than 180 cases reported in the literature.

Abnormal huge progressive enlargement and fusion of digits with limitation of joint movements (macrodactyly, syndactyly, and arthrogryposis) are usually part of a syndromic manifestation. When associated with mosaic skeletal overgrowths, vascular malformations and internal organ cysts it could be a part of the very rare Proteus syndrome. Here we are presenting a case with macrodactyly, syndactyly, arthrogyrposis and bilateral ovarian cysts. When clinical criteria remain inconclusive the diagnosis of Proteus syndrome (PS) is established by identification of a heterozygous pathogenic variant in AKT1 gene, which here could not be done because of economical constraints.

Macrodystrophia lipomatosa (ML) is a rare, non-hereditary, developmental anomaly that occurs because of the progressive proliferation of all mesenchymal elements of single or multiple digits or entire extremity, with a disproportionate increase in fibroadipose tissue. Commonly one or few digits of an extremity will be enlarged and present as macrodactyly or as enlarged limb. Lower limb involvement is more common and frequently unilateral. The diagnosis of ML is made by accurate clinical assessment and imaging modalities, such as plain X-ray, computed tomography scan, magnetic resonance imaging, and confirmed by histopathological study. In this case, we described a 10-year-old child who was brought to us with enlarged upper and lower extremities and was diagnosed as a case of ML with the help of clinico-radiological studies and presented here because of focal gigantism involving all four limbs, which is very rare.

Lipofibromatous hamartoma (LFH) is a benign tumor that causes nerve enlargement due to fatty adipose tissue infiltration around bundles of peripheral nerves. It most commonly occurs at the median nerve with associated macrodactyly. We present an uncommon case of LFH that affected a digital branch of the median nerve without macrodactyly. [ABSTRACT FROM AUTHOR]

Abstract Lipofibromatous hamartoma (LFH) is a benign tumor that causes nerve enlargement due to fatty adipose tissue infiltration around bundles of peripheral nerves. It most commonly occurs at the median nerve with associated macrodactyly. We present an uncommon case of LFH that affected a digital branch of the median nerve without macrodactyly.

Acrodysostosis is a rare syndrome of peripheral dysostosis, neurodevelopment delay, and skeletal abnormalities. The most common bone changes are peripheral dysostosis with severe brachydactyly of the lesser toes. The first ray of the feet is often not affected or may present hyperplasia resulting in an unbalanced transverse arch of the forefoot, with potential negative effects on function. Additionally, the insufficiency of the lesser toes may be associated with complex congenital hallux valgus deformities. Surgical approaches include growth plate epiphysiodesis, bulk reduction procedures, bone shortening, osteotomies, or amputation. Here, we report a case of a 14-year-old girl with acrodysostosis and severe discrepancy of the first ray and hallux valgus deformity simultaneously treated by a modified scarf osteotomy. Levels of Evidence: Level V: Case report [ABSTRACT FROM AUTHOR]

Background: Isolated macrodactyly is a severe congenital hand anomaly with functional and physiological impact. Known causative genes include PIK3CA, AKT1 and PTEN. The aim of this study is to gain insights into the genetics basis of isolated macrodactyly.Results: We enrolled 24 patients with isolated macrodactyly. Four of them were diagnosed with Proteus syndrome based on skin presentations characteristic to this disease. Targeted next-generation sequencing was performed using patients' blood and affected tissues. Overall, 20 patients carry mosaic PIK3CA pathogenic variants, i.e. p.His1047Arg (N = 7), p.Glu542Lys (N = 6), p.Glu545Lys (N = 2), p.His1047Leu (N = 2), p.Glu453Lys (N = 1), p.Gln546Lys (N = 1) and p.His1047Tyr (N = 1). Four patients who met the diagnostic criteria of Proteus syndrome carry mosaic AKT1 p.Glu17Lys variant. Variant allele frequencies of these mosaic variants obtained through next-generation sequencing range from 10 to 33%. In genotype-phenotype correlation analysis of patients with PIK3CA variant, we found that patients with the macrodactyly of the lower limbs tend to carry PIK3CA variants located in the helical domain (P = 0.005).Conclusions: Mosaic PIK3CA and AKT1 variants can be found in all of our samples with isolated macrodactyly. Insights into phenotypic and genetic spectrum of isolated macrodactyly may be helpful in perusing a more precise and effective management of isolated macrodactyly. [ABSTRACT FROM AUTHOR]

Macrodystrophia lipomatosa (ML) is a rare, non-hereditary, developmental anomaly that occurs because of the progressive proliferation of all mesenchymal elements of single or multiple digits or entire extremity, with a disproportionate increase in fibroadipose tissue. Commonly one or few digits of an extremity will be enlarged and present as macrodactyly or as enlarged limb. Lower limb involvement is more common and frequently unilateral. The diagnosis of ML is made by accurate clinical assessment and imaging modalities, such as plain X-ray, computed tomography scan, magnetic resonance imaging, and confirmed by histopathological study. In this case, we described a 10-year-old child who was brought to us with enlarged upper and lower extremities and was diagnosed as a case of ML with the help of clinico-radiological studies and presented here because of focal gigantism involving all four limbs, which is very rare. [ABSTRACT FROM AUTHOR]

• Proteus Syndrome is an extremely rare case where only 200 cases has been reported. • Macrodactyly is a striking feature. • Biesker's criteria is a diagnostic tool, which assist in reaching the diagnosis. • Confirmation is by finding genetic variation in AKT1 and/or PTEN gene. • Our case had multiple intestinal lipomatosis which caused him small bowel volvulus. Proteus Syndrome is a very rare syndrome, where only 200 cases has been reported so far. We were presented with a 45 year male with features of chronic Intestinal Obstruction. On Examination he had a giant right middle finger (Fig. 1), giant left forearm, with amputated left hand, and massive abdominal distension with tenderness in upper abdomen. Proteus Syndrome (PS) is a very rare syndrome, diagnosis of which is based on Biescker's criteria, either one finding from Criteria A, or two from B, or three from C. Confirmation of the disease is by finding genetic variation in the AKT1 gene. In addition to the presence to some of the criteria in our patient, he also had numerous intestinal lipomatosis, involving almost most of his small intestine. This in addition to high riding caecum and a narrow long mesentery which contributed to the development of small Bowel volvulus. PS should be suspected whenever we encounter patients with macrodactyly and this should alert us to the possibility of other congenital anomalies. [ABSTRACT FROM AUTHOR]

We describe a case of an adult patient presenting with cubital tunnel syndrome in the setting of previously undiagnosed macrodactyly. Early diagnosis and management of macrodactyly is important to help prevent symptoms associated with compromised peripheral nerves and reduce the likelihood of the permanent motor and sensory sequelae of prolonged nerve compression. [ABSTRACT FROM AUTHOR]

Cavernous lymphangioma is a congenital malformation of lymphatic system causing dilated lymphatic sinuses that involve the skin and subcutaneous tissues. This was an interesting case of dystrophic macrodactyly of the left ring and little finger in a 18-month-old girl who presented with swollen and sausage like fingers deformity which turned out to be an isolated cavernous lymphangioma. This tumor, although rare to occur in the extremeties, must be differentiated from other congenital vascular lesions of the hand that include arteriovenous malformations and hemangiomas. Diagnosis should be solely based on histopathological analysis of the excised tissue mass. Surgical excision is usually necessary for satisfactory functional and cosmetic outcome. [ABSTRACT FROM AUTHOR]

Lipofibromatous Hamartoma (LFH) is a rare tumour affecting the peripheral nerves, mostly the median nerve. It is benign and slowly growing. Less than 100 cases have been reported in the literature, about one quarter of them are associated with macrodactyly in the field of the affected nerve. We reported a case of a 13 years old female with LFH of the median nerve at the level of the wrist associated Macrodactyly of the ipsilateral middle finger treated surgically by decompression only. [ABSTRACT FROM AUTHOR]

Lipofibromatous hamartoma is a rare, slow-growing, benign, fibrofatty tumor-like condition. The upper extremity nerves are commonly involved. It is characterized by thickened axonal bundles with epineural and perineural fibrosis and fatty infiltration around the axonal bundles. Macrodactyly is a characteristic symptom in one-third of cases. Treatment options are differentiated according to the symptomatology. The diagnosis can be made by ultrasonographic and magnetic resonance imaging findings for those obviating diagnostic biopsy. [ABSTRACT FROM AUTHOR]

Macrodystrophia lipomatosa, a hamartomatous enlargement of soft tissues leading to gigantism of a part or a whole extremity, generally affects the territory of distribution of a single nerve. In some cases, this condition may cause an entrapment neuropathy. We report the clinical, radiological, and surgical findings of a patient with isolated non-syndromic macrodactyly and giant median nerve presenting recurrent carpal tunnel syndrome (CTS). In this case, conventional magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) supported the presence of fibrohamartomatous infiltration, determining an enlargement of the median nerve and consequently an increased susceptibility to compression damage. A 57-year-old man presenting macrodactyly of the second and third finger of the right hand showed recent onset of severe hypoesthesia of the first three fingers of the right hand. He also underwent surgery for right CTS 23 years before. The electromyography/electroneurography confirmed the diagnosis of CTS. The ultrasonography showed a massive enlargement of the median nerve within the carpal tunnel, while MRI confirmed the enlargement of the median nerve with thickened hypointense bundles and interposed tissue, with increased mean diffusivity and decreased fractional anisotropy at DTI. We discuss about the use of a relatively novel imaging technique, investigating for the first time an uncommon cause of a very common entrapment neuropathy. [ABSTRACT FROM AUTHOR]

Macrodactylism or macrodactyly is referred to as congenital deformity of fingers or toes, and the corresponding incidence rate is relatively low. In this article, we describe a young male with macrodactylism of the second toe of his right foot. He was suffering from persistent pain, overgrowth, and hyperhidrosis ofthe involved toe. Radiographic examination of the right foot showed a small translucent area surrounded by hyperplasia and sclerotic bone in the second distal phalanx, in addition to increased soft tissue density and volume. Surgical resection of the bone lesion and reduction of the soft tissue bulk were performed. Pathological findings showed osteoblast hyperplasia, which was diagnosed as osteoid osteoma, and noabnormal findings were seen in the skin. Symptoms of pain and hyperhidrosis disappeared postsurgery and did not recur over the subsequent 2-year follow-up. As far as we know, this was a rare case of osteoid osteoma occurring in the toe that resulted in macrodactylism, which was also associated with localized hyperhidrosis. [ABSTRACT FROM AUTHOR]

Macrodactyly is a rare condition in which fingers, hands or limb growth is unregulated, resulting in overgrowth of tissues in the affected extremities. It is critical to properly assess these extremities for signalling pathway, psychological impact and potential surgical intervention, to achieve the best possible outcome for each patient. Treatment approaches can vary, and patient and family expectations weigh heavily on care complexity. Common surgical procedures may include epiphysiodeses, osteotomies, debulking procedures, carpal tunnel releases, toe transfers and amputations. The selection and timing of these surgeries is a vital component of the approach, as delayed healing and excessive scarring may occur. The purpose of this review is to assist in the navigation of decision-making and surgical timing for patients presenting with overgrowth manifesting itself as macrodactyly. [ABSTRACT FROM AUTHOR]

Mirror-image symmetry in limbs is normal in the vertebrate phenotype. Genetic and epigenetic factors regulate the differentiation, patterning, and development of the embryo and foetus. Growth after birth is influenced by hormonal and environmental factors such as nutrition. Limb size asymmetry in a child should trigger a search for associated pathology that may include neoplastic conditions, sequelae of injury, vascular, and neurogenic factors. Macrodactyly, part of the PIK3CA Related Overgrowth Spectrum, offers the physician a clinical challenge, while at the same time an opportunity to study morphology, histology, and more recently the molecular mechanisms from which the conditions arise. Collaboration between clinicians and basic scientists offers an exceptional opportunity for coordinated study and the potential for improved patient outcomes. [ABSTRACT FROM AUTHOR]

The PI3K/AKT/mTOR signaling pathway is significantly activated in rheumatoid arthritis. In addition, somatic activating mutations of the PI3K/AKT/mTOR pathway may result in PIK3CA-related overgrowth spectrum diseases, including CLOVES (Congenital Lipomatous Overgrowth, Vascular malformation, Epidermal nevi, Skeletal abnormalities/Scoliosis) syndrome. We describe the case of a young female patient, with anti-citrullinated peptide antibodies-positive rheumatoid arthritis, referred for persistent finger pain and stiffness. Examination revealed discrete macrodactyly involving two fingers, scoliosis, asymmetrical calves, venectasias, a shoulder nevus and triangular feet with a “sandal gap” between two toes. These mild dysmorphic features with early-onset and the history of surgeries for thoracic lipoma and venous malformation were strongly suggestive of CLOVES syndrome. Confirmatory mutation analysis was not performed, as blood or saliva testing is not contributive for tissue-specific localized effects in the PIK3CA-related overgrowth spectrum. Nevertheless, lack of detection of a PIK3CA mutation does not exclude the diagnosis in patients fulfilling clinical criteria. Due to the patient’s wish to plan a pregnancy, therapy consisted in sulfasalazine and hydroxychloroquine, along with orthotic correction of leg length discrepancy. Overgrowth syndromes and arthritis may share common pathways. Mild macrodactyly should be differentiated from dactylitis. Diagnosing patients with minimal dysmorphic features within the PI3K-related overgrowth spectrum may help design better care strategies, in the quest for personalized medicine.

Macrodactyly of the foot is an extremely rare congenital malformation characterized by an increase in the size of all the elements or structures of a digit or digits. Most sources indicate that macrodactyly affects the hand more often than the foot. This rare medical condition usually requires surgical intervention with a precise preoperative plan and postoperative rehabilitation. We present a case of macrodactyly of the right foot in which surgical reduction of the foot under assistance of 3-dimensional image technology was performed with satisfying cosmetic and functional outcomes. [ABSTRACT FROM AUTHOR]

Somatic PIK3CA mutations may relate to pathogenesis of isolated macrodactyly. We set up to test the association between PIK3CA mutations with isolated macrodactyly in order to establish a more accurate and molecular mechanism-based diagnosis and classification. DNA extracted from affected tissues in 12 individuals with isolated macrodactyly was tested for PIK3CA mutation using targeted Sanger DNA sequencing. Ten patients had macrodactyly in the foot and two in the hand. Nine of the 12 patients were found to carry a low-level, mosaic PIK3CA mutation. The mutations identified, p.His1047Arg, p.His1047Leu, p.Glu545Lys, and p.Glu542Lys, are codons frequently mutated in cancers. Among all tissues tested, adipose had the highest mutation detection rate, followed by nerve and skin. Our results indicate that a high proportion of isolated macrodactyly patients carry a pathogenic PIK3CA mutation. Affected adipose, nerve and skin tissues are ideal for PIK3CA mutation analysis. [ABSTRACT FROM AUTHOR]