Limb Hypertrophy Research Articles

Isolated Lateralized Overgrowth - Phenotypic Spectrum and Molecular Alterations.

To evaluate the molecular aberrations at 11p15.5 locus in thirty-two patients with isolated lateralized overgrowth (ILO). Among selected 32 cases of ILO, methylation-sensitive multiplex ligation-dependent probe amplification (MS-MLPA) was performed initially followed by short tandem repeats (STR) marker analysis to confirm uniparental disomy (UPD). In those patients with normal MLPA reports, cyclin dependent kinase inhibitor 1C (CDKN1C) gene and whole exome sequencing was performed. Molecular analysis by MS-MLPA showed methylation aberrations in 28% (9/32) of patients. Gain of methylation at IC1 imprinting center (H4, H7) and loss of methylation at IC2 (H6, H9) was observed in 2 patients each. Uniparental disomy was observed in 9% cases. Except one, all patients with methylation aberration had more than one limb hypertrophy. Two patients (H22/H29) also had loss of methylation at IC1. Though this molecular alteration is specifically associated with Silver Russel syndrome (SRS), but the affected children did not completely fulfill the diagnostic criteria for SRS. In a recent study, a discrepancy was reported between the diagnosis of Beckwith-Wiedemann syndrome (BWS)/SRS and the molecular findings in the patients. Many times, it is very difficult to differentiate between hemi hypertrophy/hemi hypotrophy. Patients, in whom no aberrations were detected on MS-MLPA, whole exome sequencing (WES) was performed and no pathogenic variant was identified. Thus, ILO may be considered as a mild presentation on the extreme edge of BWS spectrum with methylation aberration and UPDin one thirdof cases which has implications in follow up.

Body morphology and handgrip strength parameters of the female canoe slalom paddlers.

Introduction: Canoe slalom is a physically very demanding discipline, in which body constitution, body composition, and relative strength are significant factors in high performance. Although anthropometric and strength parameters are relatively well-studied in male athletes, there is a lack of evidence for any conclusions in women. Therefore, the objective of this study was to determine the morphology and upper-limb strength parameters of female canoe slalom paddlers and identify whether morphological differences exist between performance groups. Methods: Altogether, 63 female competitors of the 2023 ICF Canoe Slalom World Cup (n = 29) and 2023 ICF Canoe Slalom World Ranking Competition (n = 34) in Prague (Czech Republic) were examined with a battery of anthropometric tests, segmental bioimpedance analysis, and handgrip strength test. The athletes were divided into groups according to age and performance: elite athletes belonging to the world top 10 according to the ICF World Ranking (WORLD, n = 7), international-level athletes competing during the World Cup (ELITE, n = 22), international-level junior athletes competing in the World Ranking Race (JUNIOR, n = 17), and other lower performance-level athletes competing in the World Ranking Race (REST, n = 17). Results: Female slalom paddlers are, in general, of average body height (∼165cm), lower body mass (∼60kg), BMI (∼22kg/m2), and body fat (∼20%) and without exceptional anthropometric dimensions and proportions. However, differences were detected when performance was factored in. Female paddlers belonging to the world TOP 10 have the largest circumferences of arms and forearms, and their somatotype is more mesomorphic, with a lower proportion of total body fat and a higher proportion of muscle mass. In addition, the WORLD group differs significantly in upper-limb strength. Discussion: The results shows the significance of muscular strength and power for canoe slalom athletes and the importance of well-developed musculature in operating the boat in the unstable environment. Being a successful female canoe slalom athlete requires a well-developed musculature, maximizing strength capabilities while maintaining a low body weight through limited hypertrophy of the lower limbs and a low level of body fat.

Recurrent hematuria involving urinary system with Klippel-Trenaunay syndrome: A case report.

Klippel-Trenaunay syndrome (KTS) is a rare congenital venous malformation, it had been found to be caused by mutations of the phosphatidylinositol 4, 5-diphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. Currently KTS is defined as a triad of skin wine pigmented spots, varicose veins and malformations of the lower extremities, and hypertrophy of bone and soft tissue, involving urinary system up to 6% to 30%. When the urinary system is involved, KTS is often presented as painless massive gross hematuria. This article describes a woman who was hospitalized with painless massive gross hematuria. Physical examination revealed significant hypertrophy of the right lower limb with varicose veins, port-wine stains in the skin, and right perineal hemangiomatous changes with swelling. The patient was admitted to hospital 4 times for repeated hematuria and infection. By physical examination, CT urography, ureteroscopy and cystoscopy, the patient was diagnosed to have Klippel-Trenaunay syndrome, involving the urinary system. The patient hematuria improved after multiple indwelling D-J tubes and anti-inflammatory treatment. The final symptoms of hematuria improved significantly, follow-up so far has not recurred. This case presents the possibility of painless gross hematuria with KTS. Most of patients can be improved by conservative treatment. Cystoscopic laser therapy is the preferred treatment for poor bleeding control. Cystectomy and nephrectomy should be considered when life-threatening.

A rare presentation of pupillary block glaucoma and persistent tunica vasculosa lentis in Klippel–Trenaunay syndrome

Phacomatoses are a group of neurocutaneous disorders characterized by vascular and pigmentary birthmarks, often involving multiple organ systems. Klippel–Trenaunay syndrome (KTS), a rare phacomatosis, is characterized by the classical triad of cutaneous capillary hemangiomas, venous malformations, and soft tissue overgrowth. Glaucoma secondary to angle dysgenesis, raised episcleral venous pressure, or excess angle pigmentation is observed. We report a case of KTS that presented with cutaneous capillary hemangiomas and limb hypertrophy along with unilateral buphthalmos. This eye was noted to have persistent tunica vasculosa lentis and persistent pupillary membrane with pupillary block glaucoma that was treated with pupilloplasty. To the best of our knowledge, this mechanism of glaucoma in KTS has not been reported before. The purpose of this article is to document this rare presentation as well as highlight the importance of detecting the underlying mechanism for appropriate management.

Hoffmann’s syndrome in the differential work-up of myopathic complaints: a case report

BackgroundHoffmann’s syndrome is a rare form of hypothyroid myopathy in adults, which is mainly characterized by muscular weakness and muscular pseudohypertrophy.Case presentationWe report about a 61-year-old Western European man with myalgia, myxedema and pseudohypertrophy of the calf muscles. Laboratory tests revealed significantly elevated thyroid stimulating hormone (TSH) and creatine kinase (CK). Muscle MRI showed muscular hypertrophy of the lower limbs, but no signs of myositis or myopathy (no gadolinium enhancement, no edema, no fatty degeneration). In addition, electromyography (EMG) detected spontaneous activity. After the beginning of thyroxin-therapy it took six months until the muscle weakness improved and the myalgia regressed.ConclusionsHere, we focus on diagnostic routines and typical findings to differentiate Hoffmann’s syndrome from other myopathies. Clinical hallmarks of Hoffmann’s syndrome are pseudohypertrophy and weakness of the calf muscles in combination with elevated CK and elevated TSH. EMG is well suited to detect the involvement of the muscles and muscle MRI helps to differentiate it from other myopathies. Hoffmann’s syndrome is a rare myopathy due to hypothyroidism and plays a role in the differential diagnosis of myopathic complaints even if hypothyroidism has not been detected before.

Morphological and radiological features of congenital muscular hypertrophy of the upper limb: experience from a tertiary institution.

Congenital muscular hypertrophy is a rare overgrowth disorder in the phosphatidylinositol-3-kinase related spectrum. In the past 3 years, ten patients with 11 limbs involved were treated in our centre. The aim of the study was to describe the clinical and radiological deformities of these patients. We documented the characteristic clinical morphological changes, such as hypertrophy, loss of wrist flexion, thumb hyperabduction, finger deviation and skin crease changes in the palm. Radiologically, the mean first metacarpal radial deviation angle of the affected side measured 55° (range 34 to 67) compared to the normal contralateral side 42° (range 32 to 53). The mean intermetacarpal space ratio was 1.2 (range 1.1 to 1.4) and the mean palm width ratio was 1.2 (range 1.1 to 1.3). In this study, we were able to further characterize the radiological and morphological changes of congenital muscular hypertrophy of upper limbs, which would be helpful for establishing the diagnosis and monitor treatment of this rare condition.Level of evidence: IV.

Targeted next-generation sequencing for detection of PIK3CA mutations in archival tissues from patients with Klippel–Trenaunay syndrome in an Asian population

BackgroundKlippel–Trenaunay syndrome (KTS) is a rare slow-flow combined vascular malformation with limb hypertrophy. KTS is thought to lie on the PIK3CA-related overgrowth spectrum, but reports are limited. PIK3CA encodes p110α, a catalytic subunit of phosphatidylinositol 3-kinase (PI3K) that plays an essential role in the PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway. We aimed to demonstrate the clinical utility of targeted next-generation sequencing (NGS) in identifying PIK3CA mosaicism in archival formalin-fixed paraffin-embedded (FFPE) tissues from patients with KTS.ResultsParticipants were 9 female and 5 male patients with KTS diagnosed as capillaro-venous malformation (CVM) or capillaro-lymphatico-venous malformation (CLVM). Median age at resection was 14 years (range, 5–57 years). Median archival period before DNA extraction from FFPE tissues was 5.4 years (range, 3–7 years). NGS-based sequencing of PIK3CA achieved an amplicon mean coverage of 119,000x. PIK3CA missense mutations were found in 12 of 14 patients (85.7%; 6/8 CVM and 6/6 CLVM), with 8 patients showing the hotspot variants E542K, E545K, H1047R, and H1047L. The non-hotspot PIK3CA variants C420R, Q546K, and Q546R were identified in 4 patients. Overall, the mean variant allele frequency for identified PIK3CA variants was 6.9% (range, 1.6–17.4%). All patients with geographic capillary malformation, histopathological lymphatic malformation or macrodactyly of the foot had PIK3CA variants. No genotype–phenotype association between hotspot and non-hotspot PIK3CA variants was found. Histologically, the vessels and adipose tissues of the lesions showed phosphorylation of the proteins in the PI3K/AKT/mTOR signaling pathway, including p-AKT, p-mTOR, and p-4EBP1.ConclusionsThe PI3K/AKT/mTOR pathway in mesenchymal tissues was activated in patients with KTS. Amplicon-based targeted NGS could identify low-level mosaicism from low-input DNA extracted from FFPE tissues, potentially providing a diagnostic option for personalized medicine with inhibitors of the PI3K/AKT/mTOR signaling pathway.

Congenital hypertrophy and lymphedema of the right upper limb in a child

The aim of the present study was to report a case of congenital upper limb hypertrophy associated with lymphedema in a child. An eight-year-old girl presented with a history of right upper limb oedema since birth, which was more significant in the hand. Volumetry was performed, revealing 1,838 grams in the right arm and 1,483 grams in the left arm. Intensive treatment with the Godoy method® was proposed. Treatment involved five hours per day using the RAGodoy® device, 15 minutes of cervical lymphatic therapy, and three hours of manual lymphatic therapy per day. With treatment, the volume of the right arm was reduced to 1,663 grams (reduction of 205 grams). After treatment, hypertrophy of the limb was noticed, which had been aggravated by the lymphedema. Congenital hypertrophy of the upper limb is rare in children. Its association with lymphedema has not previously been reported in the literature and could cause diagnostic difficulties.

Klippel-Trenaunay Syndrome, Segmental/Focal Overgrowth Malformations: A Review.

Klippel-Trenaunay syndrome is an uncommon, infrequent, congenital disorder characterized by a triad of capillary malformation, varicosities, and tissue and bone hypertrophy. The presence of two of these three signs is enough to obtain the diagnosis. Capillary malformations are usually present at birth, whereas venous varicosities and limb hypertrophy become more evident later. The syndrome has usually a benign course, but serious complications involving various organs, such as gastrointestinal and genitourinary organs, as well as the central nervous system, may be observed. Recently, Klippel-Trenaunay syndrome has been included in the group of PIK3CA-related overgrowth spectrum (PROS) disorders. In terms of this disorder, new results in etiopathogenesis and in modalities of treatment have been advanced. We report here a review of the recent genetic findings, the main clinical characteristics and related severe complications, differential diagnoses with a similar disorder, and the management of patients with this complex and uncommon syndrome.

Muscle power and muscle hypertrophy of the lower limbs among practitioners of functional fitness training and strength training

Muscle power and muscle hypertrophy of the lower limbs among practitioners of functional fitness training and strength training

Muscle Hypertrophy Responses to Changes in Training Volume: A Retrospective Analysis.

This study assessed associations between changes in the weekly number of sets performed and the percentage change in muscle thickness of the biceps (MTBB) and triceps (MTTB) brachii muscles. Through a retrospective analysis, sixty-eight resistance-trained subjects that participated in previous studies had their previous training volumes analyzed and compared to the volume imposed during each individual study. The relationship between variables was determined through Spearman correlation and a k-cluster analysis was performed to subdivide the participants into three groups and classified as:<0%; 0-50%, and >50% increase in the number of sets for both muscle groups. Moderate and weak correlations were observed between the alterations in training volume and changes in MTBB (rs=0.44, p=0.001) and MTTB (rs=0.35, p=0.002), respectively. A significant difference was noted between<0% to >50% for MTBB and MTTB (p=0.017; p=0.042, respectively), while no significant difference was observed between<0% to 0-50% and 0-50% to >50% (both p >0.05) for both muscle groups. In conclusion, muscle hypertrophy of the upper limbs is only weakly to moderately associated with changes in training volume of trained subjects.

Prenatal detection of Kaposiform Hemangioendothelioma with Kasabach–Merritt phenomenon: a case report

BackgroundKaposiform Hemangioendothelioma is a rare vascular neoplasm that typically presents in neonates and infancy. Most of the cases of Kaposiform Hemangioendothelioma are reported in neonates (60%) and infancy (93%), and very few cases have been reported prenatally. We describe here a case which was diagnosed prenatally in the 3rd trimester with rapid growth of upper limb and appearance of non-immune hydrops.Case presentationA 25-year-old primigravida, an antenatally booked case, presented for routine third trimester level III scan at 34-week gestation. Level I scan for nasal bone and nuchal translucency at 12 weeks and level II anomaly scan at 20 weeks were normal. Level III ultrasound scan revealed increased echogenicity and hypertrophy of soft tissues of right upper limb and trunk involving both the subcutaneous and muscular compartments. Fetal middle cerebral artery Doppler, echocardiography and magnetic resonance imaging revealed fetal anemia, cardiac failure, and non-immune hydrops. These findings with hemodynamic changes and rapid evolution were suggestive of Kaposiform Hemangioendothelioma with Kasabach–Merritt phenomenon.ConclusionThe diagnosis of Kaposiform Hemangioendothelioma should be suspected in prenatal period if there is unilateral hypertrophy of limb which has evolved rapidly over a short interval of time and shows findings suggestive of Kasabach–Merritt Phenomenon. Prenatal presentation is life threatening if it is associated with poor fetal hemodynamics. Prenatal counseling in such cases should include advice on termination of pregnancy with emphasis on neonatal management.

Limb Hypertrophy—An Uncommon Presentation Yet a Common Link among Neurocutaneous Syndromes: A Series of Three Cases

AbstractLimb hypertrophy is an unusual presentation associated with neurocutaneous syndromes. The mechanism behind this presentation may vary from case to case. Here, we describe a case series of three different syndromes linked by a common clinical finding of limb hypertrophy.

Research status of the effects of natural oligosaccharides on glucose metabolism

AbstractDiabetes is a common and frequently occurring endocrine and metabolic disease characterized by hyperglycemia with genetic tendency. At present, the drugs for diabetes include metformin, glimepiride, and acarbose. Although these drugs are effective, long‐term usage will produce secondary symptoms, such as Cushing's syndrome, limb hypertrophy, and even the risk of hypoglycemia. Many natural products have been found to treat diabetes, among which oligosaccharides are the most valuable. Oligosaccharides are low‐level oligosaccharides formed by the linkage of 2–10 monosaccharides through glycosidic bonds. Common oligosaccharides include chitosan oligosaccharides, xylooligosaccharides, konjac glucomannan, and brown algae oligosaccharides. It has the effects of reducing blood glucose, blood pressure, antioxidant, anti‐inflammatory, immune regulation, antiallergy, promoting the growth of bifidobacteria, and improving body health. With the continuous exploration of the medicinal value of natural oligosaccharides, more and more attention has been paid to their research. This review introduces some representative oligosaccharides with hypoglycemic effects, including their structural characteristics and hypoglycemic mechanism, as well as the application status and future development trend of oligosaccharides.

A case of chyluria with nephrotic-range proteinuria caused by lymphatic malformation, leading to a diagnosis of Klippel-Trenaunay syndrome.

Klippel-Trenaunay syndrome (KTS) is a rare syndrome, which is clinically diagnosed by the presence of unilateral limb hypertrophy with vascular malformation including cutaneous capillaries, veins and lymphatic vessels. Most cases typically exhibit cutaneous manifestations such as port-wine stains and limb hypertrophy from infancy, but cases with mild manifestations may remain undiagnosed. We here report a case of KTS who was diagnosed by chance chyluria. A 15-year-old girl who exhibited hematochyluria with nephrotic-range proteinuria was referred to our hospital. She had been diagnosed as idiopathic scoliosis accompanied by left lower limb hypertrophy in the past. She noticed her milky urine for the first time two months before. Immediately thereafter, she noticed edema of her left leg. Hematochyluria with nephrotic-range proteinuria was found by our initial urine examination. Magnetic resonance imaging suggested venous or lymphatic malformation along the left common iliac vein at the retroperitoneal side. Lymphoscintigraphy showed congestion of radioisotope around backside of the pancreas to the left renal hilus, suggesting an existence of lymphostasis. Based on the findings, we diagnosed the patient as KTS. After admission, hematochyluria and proteinuria were decreased and became insignificant by three days with bed rest. Her left leg edema was reduced. After taking a guidance to avoid intensive exercise, she was discharged in two weeks. Because the present case exhibited mild manifestations, diagnosis was made by urine abnormalities for the first time. The case suggests that we should be aware of the presence of undiagnosed patients of KTS due to relatively mild manifestations.

Peptide Tyrosine-Tyrosine Triggers GLP-2-Mediated Intestinal Hypertrophy After Roux-en-Y Gastric Bypass

Purpose Intestinal remodeling and adaptation of the alimentary limb after Roux-en-Y gastric bypass (RYGB) play an important role in the pathophysiological events that lead to type 2 diabetes mellitus (T2DM) improvement. Intestinal absorptive loop hypertrophy and growth following surgery have been related to GLP-2 secretion by ileal L-cells. The secretion of peptide tyrosine-tyrosine (PYY) enterohormone after a meal has been proposed as a trigger for ileal secretion of GLP-1. Our aim is to determine the role of PYY as a GLP-2 secretion modulator as an adaptation result in the alimentary limb after RYGB.MethodWe used a non-obese euglycemic rodent model. Circulating glucose, insulin, PYY, and GLP-2 were measured in the experimental and control groups. We used four groups: fasting control, Sham-operated, RYGB-operated (RYGB), and RYGB-operated and treated with BIIE0246 (RYGB + BII). BIIE0246 is a NPY2 receptor antagonist in L-cells. Intestinal glucose transporters and GLP-1 and PYY gut expression and hypertrophy were analyzed after 12 weeks of surgery.ResultsRYGB increased PYY3-36 plasma levels in rats with or without BII treatment. A high-insulin response was observed in the RYGB group but not in the control or RYGB + BII groups. BIIE0246 treatment limited plasma GLP-2 levels. In the alimentary intestinal limb, hypertrophy and SGLT1 and GLUT1 expression appeared to be reduced after RYGB compared to controls.ConclusionThe postprandial ileal PYY secretion is enhanced after RYGB. This increase mediates GLP-2 release through its binding to the Y2 receptor on L-cells. This mechanism plays a role in alimentary limb hypertrophy after surgery.Graphical abstract

Polydactyly and Single Umbilical Artery

Background: Beckwith–Wiedemann syndrome (BWS) is the most common genetic overgrowth syndrome characterized by the triad of macroglossia, macrosomia, and abdominal wall defects. Clinical Description: We report the case of a term baby girl who was born with mesoaxial polydactyly of her left foot. There were no significant antenatal events or exposure to teratogens, although a single umbilical artery (SUA) had been detected on antenatal ultrasonography. There was no evidence of in utero growth retardation. The birth weight was 3.3 kg and the perinatal transition was uneventful. The general physical and systemic examination was otherwise remarkable. Targeted search for concealed major anomalies was negative and the baby was discharged as nonsyndromic polydactyly, emphasizing the need for regular vigilant surveillance on follow-up. At 6 weeks, significant hypertrophy of the left lower limb was noted. This led the direction of evaluation toward lateralized overgrowth syndromes. Management: The application of the diagnostic algorithm prompted us to order first-tier genetic testing by methylation-specific multiplex ligation-dependent probe amplification assay. This identified aberrant DNA methylation in the chromosome 11p15 region, establishing the diagnosis of BWS. SUA and polydactyly have not been reported in combination in BWS earlier. Conclusions: Neonates with minor anomalies should always have a detailed physical examination at birth and be actively evaluated for major concealed anomalies. Since many clinical manifestations become apparent with age, it is vital that affected babies be kept under close surveillance. A rationale, individualized, step-wise approach with multidisciplinary teamwork helps in establishing the diagnosis in infants with dysmorphic features.

313 Management of pregnant woman with klippel trenaunay syndrome and severe pelvic capillary angioma: A case report

Introduction: Klippel–Trenaunay Syndrome (KTS) is a rare congenital vascular disorder characterized by the association of capillary malformations, venous varicosities, and limb hypertrophy. Pregnant women with KTS are exposed to an increased risk of aggravation of KTS symptoms, venous thromboembolic events and severe postpartum haemorrhage partly due to the physiological increase in venous pressure, venous stasis and increased cardiac output during pregnancy. Literature review reports few cases but numerous obstetrical complications.

Klippel-trenaunay syndrome with congenital heart disease and bony abnormalities: A rare case report

Although Klippel-Trenaunay syndrome (KTS) is an infrequently seen dermatological disorder with plethora of associations. It is largely a clinical diagnosis made by the presence of at least two of the three classic findings. We are reporting a 16-year-old male child who presented to us with the limb hypertrophy, portwine stains, congenital heart disease, and bony abnormality. Multiple associations of KTS make it an interesting case.

Effect of different eccentric tempos on hypertrophy and strength of the lower limbs.

The purpose of this study was to evaluate the effects of altering the duration of the eccentric phase in isotonic contractions on muscle hypertrophy and strength of the quadriceps femoris. Ten healthy young adults (8 men and 2 women: Height: 173.3 ± 9.6 cm: Body mass: 69.84 ± 10.88 kg; Body fat: 19.47 ± 8.42%; Age: 25.3 ± 4.8 years) performed unilateral isotonic knee extension exercise, whereby each leg was randomly allocated to perform the eccentric phase of movement with a duration of either 2 seconds (G2S) or 4 seconds (G4S). Both conditions carried out the concentric phase of each repetition at a 1 second duration with no rest in the transition phases. Each condition performed 5 sets using 70% of 1 repetition maximum until muscle failure with 3 minutes of rest between sets for 8 weeks. The change in muscle strength was assessed by 1RM knee extension and muscle thickness was assessed by A-mode ultrasound. For each outcome variable, linear mixed-effects models were fit using restricted maximum likelihood. Hedges’ g effect sizes were calculated to provide insights into the magnitude of effects. Results showed all muscles increased in size over time; mean effects were similar in all muscles except for the vastus medialis, which favored the G4S condition. Conversely, only a trivial and highly variable effect was observed between interventions for strength gain. Our results suggest different eccentric durations produce similar increases in hypertrophy of the vastus lateralis and rectus femoris; however, the vastus medialis showed greater growth from the slower eccentric duration. Eccentric duration did not differentially affect strength-related adaptations.