Myofibrillar myopathy (MFM) type 8, caused by PYROXD1 gene variants, has recently been identified and has been rarely reported to date. Our aim was to report the first case of MFM type 8 from Tunisia with delayed diagnosis due to a non-specific clinical presentation. Results:A 36-year-old North-African male presented to our neurology department with a 15-year history of progressive muscle weakness leading to difficulty in walking and standing without dysphagia or facial weakness. His family history was unremarkable, with no similar cases reported. His medical history was insignificant, with no previous or current medication. Neurological examination noted symmetrical proximal motor deficit in all four limbs with calf pseudohypertrophy and hyporeflexia in lower limbs. Proximal muscular dystrophy was suspected. Normal levels of blood creatine kinase (CK) and lactate dehydrogenase were noted, and the immunological work-up was negative. A muscle biopsy of the anterior tibialis was performed, revealing a histopathological pattern consistent with proximal muscle dystrophy suggestive of Limb-Girdle Muscle Dystrophy (LGMD). Whole exome sequencing (WES) was performed, revealing a homozygous variant NM_024854.3: c.464A > G on the PYROXD1 gene. The diagnosis of MFM type 8 was retained, and physical therapy was prescribed. At 2-year follow-up, a slight worsening of motor deficit was observed, but his modified Rankin's scale remained stable at 3. Conclusions:We reported the first Tunisian case of MFM type 8 associated with a well-known pathogenic variant in the PYROXD1 gene. This case mimics LGMD with a moderate deficit and slow progression. MFM type 8 can present with different phenotypes, making the diagnosis difficult.
Introduction:Dysferlinopathies are a spectrum of autosomal recessive muscular dystrophies caused by mutations in the dysferlin gene (DYSF), leading to heterogeneous phenotypes, mainly limb-girdle muscular dystrophy type 2R (LGMDR2) and Miyoshi distal myopathy (MMD1). In Morocco, dysferlinopathies accounted for 18% of all limb-girdle muscular dystrophies, ranking second after sarcoglycanopathies. Methods:We retrospectively analyzed 28 confirmed cases, diagnosed either by dysferlin deficiency or DYSF mutation. Results:The median age at examination was 25,5 years (21-33). Twelve patients (43%) were female, and 19 (68%) had consanguineous parents. The proximodistal phenotype was predominant (50%), followed by LGMDR2 (39%) and MMD1 (11%). Selective biceps brachii involvement was observed in 68% of patients. Seven patients (25%) showed hypertrophy of the extensor digitorum brevis muscle, and two (7%) presented with severe genu recurvatum. In addition to dystrophic lesions, muscle biopsy revealed inflammatory infiltrates in 15 cases (58%), leading to an initial misdiagnosis of inflammatory myopathy in two cases. Dysferlin deficiency confirmed the diagnosis in 26 cases, while two others had homozygous DYSF variants. Four patients received corticosteroids, with clear improvement in only one. Overall, disease progression was slow, although two patients lost ambulation at the ages of 26 and 32. Regular physical activity appeared to have a beneficial effect in most patients.
Periodic paralyses (PPs) are rare skeletal muscle ion channelopathies caused by mutations in skeletal muscle sodium, calcium, and potassium channel genes. PPs can be divided into primary periodic paralyses (PPPs) and secondary PPs by the aetiology. Secondary PPs are common in hyperthyroidism, primary aldosteronism, renal tubular acidosis, or be related to other causes such as medication intake or potassium loss from the digestive or renal systems. Both conditions are characterized by episodic flaccid muscle weakness. Primary PPs are classified as Hypokalemic Periodic Paralyse, (HypoPP), normokalemic periodic paralysis (NormoPP), Hyperkalemic Periodic Paralyses (HyperPP), and Andersen-Tawil Syndrome (ATS). Common features are autosomal dominant inheritance, typical onset in the first or second decades, and episodic attacks of flaccid weakness often triggered by diet or rest after exercise. The article focuses on the key role of potassium in promoting and/or preventing paralytic attacks and in avoiding them through appropriate dietary measures.
Introduction:Treatment with Risdiplam has been recently extended to adult patients with Spinal Muscular Atrophy (SMA). We describe the experience of a single neuromuscular centre in Italy in treating adult SMA patients with risdiplam and analyze motor function during a follow-up period of 24 months. Patients and methods:Twelve patients with type 2 or 3 SMA (three with SMA type 3, five with SMA type 3a and four with type 3b, age range: 24-61) were included. Of them, nine were "sitter" and three were "walker"patients. The Revised Upper Limb Module (RULM) and the Hammersmith Functional Motor Scale Expanded (HFMSE) were recorded at baseline and every six months. Treatment adverse events were collected at every follow-up visit. Results:All the patients reached the 24-month follow-up. Based on the HFMSE score, 50% showed an improvement compared to the baseline total scores, 41,7% remained stable, and 8.3% experienced slight clinical worsening. Based on the RULM scores, the percentages were comparable: 50% demonstrated an improvement compared to the baseline total scores, 41,7% remained stable and 8,3% slight clinical worsening. The best results were observed in the patient "walker" group. The most common adverse events were transient gastro-intestinal problems and headache. Conclusions:Our study confirms that risdiplam is well tolerated. Half of the patients improved after risdiplam initiation and about 42% remained stable. Most patients stated to be satisfied with the medication. Longitudinal studies are needed to better understand the long-term effects of risdiplam in adult SMA.
Hypokalemic periodic paralysis (HypoPP) is a rare disease that consists of attacks of flaccid paralysis that often occur at night or early in the morning. Some patients with HypoPP may develop permanent muscle weakness and permanent myopathy. Four phenotypes of disease have been described: 1) no symptoms; 2) periodic paralysis and absence of permanent weakness; 3) periodic paralysis and permanent paralysis; 4) permanent weakness and absence of periodic paralysis. Vacuolar alterations are present in the muscles of all patients affected by HypoPP. In general, vacuoles are heterogeneous in size and content. Vacuoles are present in both fiber types and are not exclusive to any muscle fiber type, age, or phenotype. Generally, vacuoles contain glycogen but may also contain autophagosomes, fibrillar proteins, central nuclei, and myofiber invaginations. Magnetic resonance shows that fat accumulation of various extension is present in the muscle of patients with HypoPP. Water accumulation may also be present whereas atrophy is limited. Fat accumulation tends to increase with time together with a decrease of muscle strength. Permanent weakness and myopathy impairs significantly the quality of life. No treatment is currently available. The aim of this review is to define the characteristics and outcome of permanent weakness and myopathy in patients with HypoPP.
Introduction:Focal myositis is a rare inflammatory disease characterised by localised involvement of a single muscle or muscle group. Involvement of the sternocleidomastoid muscle represents an extremely rare localisation. Materials and methods:We report the case of a 78-year-old woman who developed progressive left laterocervical swelling and pain following a respiratory infection. Extensive clinical and radiological investigations were performed; however, a definitive diagnosis was achieved only after muscle biopsy. Results:The patient initially responded to corticosteroid therapy but subsequently developed steroid dependence. For long-term disease control, methotrexate was introduced as a steroid-sparing agent. The clinical course was notable for recurrent disease exacerbations associated with fever. Discussion:This case presents several distinctive features, including occurrence in an elderly patient, the presence of fever during disease flares, and a steroid-dependent course requiring second-line immunosuppressive therapy. These aspects contribute to the diagnostic and therapeutic complexity of focal myositis, particularly in atypical localisations. Conclusion:Our experience highlights the diagnostic challenges associated with this rare entity and suggests that prolonged immunosuppressive treatment may be necessary in selected patients with focal myositis.
Introduction:Muscular diseases (MDs) are rare genetic conditions marked by progressive motor, cardiac, and respiratory decline, often accompanied by significant psychological and social challenges. Anxiety, depression and reduced quality of life (QoL) are common among individuals with MDs, highlighting the importance of integrating psychological assessment and support into multidisciplinary care. Although evidence on psychosocial interventions remains limited, emerging research suggests that nature-based therapeutic activities -particularly adapted sailing - can reduce anxiety and enhance psychological well-being in people with various disabilities. Recent studies indicate improvements in state anxiety, QoL, and respiratory perception associated with exposure to the marine environment. Patients and methods:Based on this evidence, the multidisciplinary team of the Naples NeMO Clinical Center developed the "Anima Libera" project, a sailing-based therapeutic program aimed at evaluating the psychological and clinical effects of an integrated intervention for individuals with muscular diseases. The project included 12 patients with different types of muscular dystrophies aged between 28 and 55 years. Results:All patients showed an improvement in psychological well-being and respiratory parameters. Discussion and conclusions:These data, although preliminary indicate that sailing could act as a complementary therapeutic tool within psychological support and rehabilitation programs for patients with muscle diseases.
Pathogenic variants in SPG7 cause autosomal dominant progressive muscular atrophy. SPG7 encodes an inner mitochondrial membrane protein, paraplegin. Burgeoning lines of evidence have continued to suggest important roles for paraplegin in mitochondria function. Here we report elevated levels of biochemical markers of mitochondria dysfunction [3-methylglutaconic acid and 3-methylglutaric acid (in urine and blood) as well as plasma Growth Differentiation Factor 15 (GDF 15)] in a 65-year-old woman with a heterozygous pathogenic SPG7 variant [c.1529C > T (p.Ala510Val)], and evidence of muscle disease as well as chronic cerebral vasculopathy.
Introduction:Fat embolism syndrome (FES) is a rare but potentially life-threatening complication of long bone fractures, typically described in high-energy trauma. In patients with Duchenne Muscular Dystrophy (DMD), even minor trauma can result in FES, owing to long-standing osteoporosis and prolonged corticosteroid therapy, and the recognition can be challenging. Materials and methods:We report a case series of three non-ambulatory patients with DMD who developed fat embolism syndrome following traumatic events. Clinical presentation, diagnostic challenges, and management strategies were retrospectively analyzed. Results:All three patients presented with features consistent with FES, with diagnostic difficulties related to atypical mechanisms of injury and overlapping neuromuscular symptoms. Timely supportive management led to favorable clinical outcomes in all cases. Discussion:These cases illustrate the critical need to closely consider FES in DMD patients who experience unexplained respiratory or neurological decline following trauma. Conclusion:Prompt recognition and a multidisciplinary approach are critical to minimizing morbidity and supporting recovery.
Giant Cell Myositis (GCMm) is an exceptionally rare inflammatory myopathy, historically reported in association with Myasthenia Gravis (MG), Thymoma, or Giant Cell Myocarditis (GCMc). The prognosis is often dictated by the frequently co-occurring, highly lethal GCMc. We describe the case of a 31-year-old male presenting with a three-month history of progressive, painful, and diffuse pseudohypertrophy of the lower extremities. Laboratory findings, including normal creatine kinase, were largely unremarkable, but a muscle biopsy demonstrated the pathognomonic infiltration by multinucleated giant cells. Extensive work-up, including cardiac magnetic resonance imaging and a full autoantibody panel, showed no evidence of cardiac, ocular, or associated thymic disease or MG. This is, to our knowledge, the first reported case of GCMm presenting as an isolated skeletal muscle disease without any known associated systemic conditions, underscoring the importance of considering GCMm in the differential diagnosis for unexplained limb pseudohypertrophy, even in the absence of typical comorbidities or profound muscle weakness.
Objective:Thymidine kinase 2 (TK2) deficiency is a rare mitochondrial disease with variable phenotypes and emerging treatments. Prompt diagnosis is essential to optimize patient outcomes and management. To assess the current awareness, diagnostic approaches, and readiness to include TK2 screening in Italian neuromuscular clinical practice. Methods:A nationwide survey was distributed to AIM-affiliated clinicians. The questionnaire assessed TK2 awareness, diagnostic pathways, gene panel content, and attitudes towards screening in unresolved cases. Results:while awareness of TK2 deficiency was almost universal, inclusion of TK2 in genetic panels varied: 85% in metabolic myopathy panels, 56% in LGMD panels. Screening for TK2 in genetically unsolved SMA, FSHD, and OPMD phenotypes was inconsistent. Conclusions:Although awareness of TK2 deficiency is widespread, diagnostic strategies are inconsistent. Standardizing TK2 inclusion in NGS panels and promoting differential screening are key steps toward earlier diagnosis in the view of future treatment options.
Objectives:This case report explores the feasibility and effects of long-term physical exercise (PE) in a patient with TRPV4-related scapuloperoneal spinal muscular atrophy (SPSMA). Methods:We describe a 26-year-old male who regularly engaged in supervised PE since age 21. He underwent annual clinical evaluations and laboratory assessments every 25 months to monitor maximal oxygen consumption (V̇O2max), muscle strength, body composition, and emotional well-being. Results:Over five years, the clinical condition remained stable. The patient showed V̇O2max and handgrip strength values comparable to athletic cohorts; body composition aligned with reference values for age- and sex-matched healthy individuals; and limb muscle strength was preserved over time. Additionally, he maintained an active working life and consistently reported positive emotional well-being throughout the follow-up period. Conclusions:This report provides preliminary data supporting the feasibility and potential benefits of long-term PE in the management of TRPV4-related SPSMA.
Congenital myopathies are a heterogeneous group of rare inherited muscle disorders. Despite the good sensitivity of whole-exome sequencing in detecting pathogenic variants, many cases remain molecularly unsolved. Here, we present the case of a woman with congenital myopathy that remained unsolved for many years, in which the application of whole-genome sequencing enabled the identification of a novel deep intronic mutation in the MYH7 gene. A 22-year-old woman developed muscle weakness since infancy, with frequent falls, toe-walking, and difficulty climbing stairs. Muscle biopsy revealed atrophy of type 1 fibers relative to type 2, consistent with fiber-type disproportion. After a long "molecular odyssey," whole-genome sequencing performed on the patient-parents trio identified a de novo deep intronic variant in MYH7. This case further underscores the importance of pursuing the search for the causative gene to enable more accurate clinical monitoring and tailored health care.
Objectives:Collagen 6-related Bethlem myopathy and LDLR-related familial hypercholesterolemia are presumed to be quite rare in the general population. Case report:Here, we present the clinical findings from a 65-year-old man with comorbid Bethlem myopathy and familial hypercholesterolemia to highlight some important molecular diagnostic considerations and clinical management implications.
Background:Xp21 contiguous gene deletion syndrome is a rare X-linked disorder involving deletions of DMD, GK, and NR0B1 (DAX1), leading to a combination of Duchenne muscular dystrophy, glycerol kinase deficiency, and congenital adrenal hypoplasia. Diagnosis can be delayed due to overlapping symptoms, especially in critically ill infants. Case Reports:We describe two male infants presenting in early life with adrenal insufficiency, electrolyte imbalance, hyperpigmentation, and hypotonia. Biochemical findings included elevated ACTH, low cortisol, high CK, and pseudo-hypertriglyceridemia. In the first case, delayed diagnosis led to sudden death at 7 months. In the second case, early clinical suspicion enabled timely genetic testing and family screening. MLPA revealed DMD gene deletion in both cases. In the second case, molecular karyotyping confirmed deletion at Xp21.3-p21.1; the mother and sister were also carriers. Conclusion:Clinicians should consider Xp21 syndromes in male infants with adrenal insufficiency and neuromuscular or metabolic signs. Early recognition and genetic testing are crucial for accurate diagnosis, effective management, and informed family counseling.
Introduction:Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease linked to the X chromosome caused by the lack of functional dystrophin. About 10-15% of cases are caused by nonsense mutations, and their natural history is thought to be similar to DMD by other causes. Ataluren is a new therapeutic option that promotes the readthrough of nonsense mutations leading to the production of functional dystrophin proteins. Objective:To describe the natural history of patients with nonsense mutations DMD (nmDMD) and evaluate the impact of corticosteroids and ataluren on disease progression. Methods:It is a retrospective, longitudinal case-series study of all male patients with nmDMD treated at Sant Joan de Déu Hospital in Barcelona, Spain, since 2007. Results:28 patients from 3.7 to 22 years old were included. The mean age at symptom onset was 3.5 years, and at genetic diagnosis was 4.5 years. All patients were treated with corticosteroids, and 17 patients also received ataluren. Patients treated with ataluren delayed the loss of ambulation by three years (14 vs 10.9 years). No patients treated with ataluren required non-invasive ventilation. Conclusions:Patients with DMD caused by nonsense mutations present a similar phenotype to those with DMD with other types of mutations. Patients treated with ataluren delayed the loss of ambulation and appeared to maintain upper limb and respiratory function better than those not treated with ataluren.
Objectives:Some muscular dystrophies, such as myotonic dystrophy type 1 and 2 (DM1 and DM2), facioscapulohumeral muscular dystrophy (FSHD), and oculopharyngeal muscular dystrophy (OPMD), are caused by genetic mutations that may affect the expression and function of various cancer-related genes. We assessed the frequency and type of cancers and benign tumors in patients with DM1, DM2, FSHD, and OPMD. Methods:We conducted a single-center, retrospective, cross-sectional study on patients with DM1, DM2, FSHD, and OPMD at our institution from January 2000 to September 2023. Results:Seventy seven (46 female) DM1, 20 (15 female) DM2, 40 (18 female) FSHD, and 46 (22 female) OPMD patients were included, among which 22 (28.57%), 9 (45%), 7 (17.5%), and 15 (32.61%) patients had at least one cancer, respectively. Median age (range) of patients where presence or absence of cancer was ascertained was 65 (18-87), 63.5 (45-86), 61 (27-83), and 71.5 (40-82) years, respectively (P < 0.0001). Overall, non-sex-related cancers were more frequent than sex-related cancers among all patients together. Independent to sex and age, DM1 patients had an increased risk of non-sex-related cancers compared to non-DM cases. Melanoma (P < 0.01) and testicular (P < 0.05) cancers were significantly more frequent in DM2 and OMPD patients, respectively. DM patients had also increased risk of non-sex related benign tumors (including skin and thyroid benign tumors) compared to non-DM patients. Conclusions:Our study highlights the differences in the prevalence of cancers and benign tumors among patients with DM1, DM2, FSHD, and OPMD, underscoring the potential need for regular screening for specific cancers.
