Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively. Results: Among the 9 children, 6 were boys and 3 were girls. The age of last visit or follow-up was 5.0 (2.7,6.8) years. The main clinical manifestations included motor retardation, mental retardation, multiple malformations, and skeletal deformity. Cases 1-4 were all all boys, showed myopathic gait, poor running and jumping, and significantly increased level of serum creatine kinase. Disease-causing variations in Duchenne muscular dystrophy (DMD) gene were confirmed by genetic testing. The 4 children were diagnosed with DMD or Becker muscular dystrophy combined with a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, and cerebral cavernous malformations type 3, respectively. Cases 5-9 were clinically and genetically diagnosed as COL9A1 gene-related multiple epiphyseal dysplasia type 6 combined with NF1 gene-related neurofibromatosis type 1, COL6A3 gene-related Bethlem myopathy with WNT1 gene-related osteogenesis imperfecta type XV, Turner syndrome (45, X0/46, XX chimera) with TH gene-related Segawa syndrome, Chromosome 22q11.2 microduplication syndrome with DYNC1H1 gene-related autosomal dominant lower extremity-predominant spinal muscular atrophy-1, and ANKRD11 gene-related KBG syndrome combined with IRF2BPL gene-related neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy. DMD was the most common, and there were 6 autosomal dominant diseases caused by de novo heterozygous pathogenic variations. Conclusions: Pediatric patients with coexistence of double genetic diagnoses show complex phenotypes. When the clinical manifestations and progression are not fully consistent with the diagnosed rare genetic disease, a second rare genetic disease should be considered, and autosomal dominant diseases caused by de novo heterozygous pathogenic variation should be paid attention to. Trio-based whole-exome sequencing combining a variety of molecular genetic tests would be helpful for precise diagnosis.
Humans ; Abnormalities, Multiple ; Retrospective Studies ; Intellectual Disability/genetics* ; Bone Diseases, Developmental/complications* ; Tooth Abnormalities/complications* ; Facies ; Muscular Dystrophy, Duchenne/complications* ; Muscular Atrophy, Spinal/complications* ; Carrier Proteins ; Nuclear Proteins

Aged ; Creatine Kinase ; blood ; Female ; Humans ; Hypothyroidism ; complications ; Muscular Diseases ; etiology ; Rhabdomyolysis ; etiology ; Thyrotropin ; blood

BackgroundFacioscapulohumeral muscular dystrophy (FSHD) is characterized by asymmetric muscular deficit of facial, shoulder-girdle muscles, and descending to lower limb muscles, but it exists in several extramuscular manifestations or overlapping syndromes. Herein, we report a "complex disease plus" patient with FSHD1, accompanied by peripheral neuropathy and myoclonic epilepsy.

MethodsStandard clinical assessments, particular auxiliary examination, histological analysis, and molecular analysis were performed through the new Comprehensive Clinical Evaluation Form, pulsed-field gel electrophoresis-based Southern blot, Multiplex Ligation-dependent Probe Amplification (MLPA), whole exome sequencing (WES), and targeted methylation sequencing.

ResultsThe patient presented with mild facial weakness, humeral poly-hill sign, scapular winging, peroneal weakness, drop foot, pes cavus, and myoclonic epilepsy. Furthermore, electrophysiology revealed severely demyelinated and axonal injury. The muscle and nerve biopsy revealed broadly fiber Type II grouping atrophy and myelinated nerve fibers that significantly decreased with thin myelinated fibers and onion bulbs changes. Generalized sharp and sharp-slow wave complexes on electroencephalography support the diagnosis toward myoclonic epilepsy. In addition, molecular testing demonstrated a co-segregated 20-kb 4q35-EcoRI fragment and permissive allele A, which corresponded with D4Z4 hypomethylation status in the family. Both the patient's mother and brother only presented the typical FSHD but lacked overlapping syndromes. However, no mutations for hereditary peripheral neuropathy and myoclonic epilepsy were discovered by MLPA and WES.

ConclusionsThe present study described a "tripe trouble" with FSHD, peripheral neuropathy, and myoclonic epilepsy, adding the spectrum of overlapping syndromes and contributing to the credible diagnosis of atypical phenotype. It would provide a direct clue on medical care and genetic counseling.

Adult ; Child ; Epilepsies, Myoclonic ; complications ; Evoked Potentials, Visual ; Humans ; Male ; Muscle, Skeletal ; Muscular Dystrophy, Facioscapulohumeral ; complications ; Peripheral Nervous System Diseases ; complications

Although it is well known that the respiratory failure is a major cause of death in most patients with chronic neuromuscular disease, predominant respiratory dysfunction without severe involvement of limb muscles is an unusual complication of mitochondrial myopathy in adult age. We experienced two cases of mitochondrial myopathy with severe involvement of respiratory function and only mild involvement of limb muscles. One is a 16 year old female and another is a 22 year old male. The diagnosis is based on morphologic characteristics of "ragged red fibers" under the light microscope and abnormal mitochondrias on the electron microscope in the muscle biopsy.
Adolescent ; Adult ; Electromyography ; Female ; Human ; *Mitochondria, Muscle/ultrastructure ; Muscular Diseases/*complications ; Respiration, Artificial ; Respiratory Insufficiency/*etiology/therapy

Colchicine plays an important role in the treatment of gout and some other diseases. Besides gastrointestinal symptoms, myopathy has been reported as a rare side effect of colchicine in some patients. We report a case of myopathy in a patient with chronic kidney disease caused by high-dose colchicine, and then review literature on colchicine-induced myopathy, so as to provide some experience for the clinical diagnosis, treatment and medication safety. A 51-year-old male patient with 10 years of gout and 5 years of chronic kidney disease history and irregular treatment was admitted to the hospital with complaint of recurrent left wrist arthralgia and emerging lower extremities myalgia after intake of 40-50 mg colchicine in total within 20 days. Laboratory examinations showed significantly increased creatine kinase (CK) and then colchicine-induced myopathy was diagnosed preliminarily. After withdrawl of colchicine and implementation of hydration, alkalization and intramuscular injection of compound betamethasone, the symptoms of arthralgia and myalgia were relieved within 3 days and CK decreased to normal range gradually. According to literature reports, colchicine related myopathy was mostly characterized by proximal myasthenia and myalgia, accompanied by elevated CK level, which usually occurred days to weeks after initial administration of colchicine at the usual dosage in patients with renal impairment or a change in the underlying disease state in those receiving long-term therapy, and the features might remit within three to four weeks after the drug was discontinued. Electromyography of proximal muscles showed myopathy marked by abnormal spontaneous activity and muscle pathology waa marked by accumulation of lysosomes and autophagic vacuoles. Chronic kidney disease, liver cirrhosis, higher colchicine dose and concomitant cytochrome P450 3A4 (CYP3A4) inhibitors were associated with increased risk of myo-pathy. Based on the similar efficacy and lower adverse reaction rate compared with larger dosage, small dose of colchicine was recommended by many important current guidelines and recommendations in the treatment of gout. In consideration of potential risks, colchicine should be used with caution in patients with kidney or liver impairment, and in those taking CYP3A4 or P-glycoprotein inhibitors. For those patients, the drug dose should be adjusted and the latent adverse reactions should be monitored carefully.
Colchicine/adverse effects* ; Gout/drug therapy* ; Humans ; Kidney ; Male ; Middle Aged ; Muscular Diseases/chemically induced* ; Renal Insufficiency, Chronic/complications*

OBJECTIVETo analyze the clinical characteristics and effects of rehabilitation treatment on hemophiliacs with iliopsoas hemorrage.

METHODSThe hemophilia patients with iliopsoas bleeding treated in Peking Union Medical College Hospital between January 2006 to December 2010 were enrolled. The clinical characteristics including symptoms, signs, complications, and rehabilitation treatment were analyzed retrospectively.

RESULTSAll of the forty-one hemophiliacs with iliopsoas bleeding were male, 20 cases wee the left bleeding, 18 the right, and 3 the bilateral. The median median age was 18 (6 - 61) years old(y). The median age of the iliopsoas bleeding for the first time was 17 (6 - 20) y. 34 patients accompanied with femoral nerve injury, 19 of them had secondary knee bleeding on the same side. 20 patents had quadriceps atrophy. Pelvic pseudotumor developed in 2 patients and permanent abnormal posture in 2 patients. The main finding of the ultrasound image was low-echo mass in iliopsoas muscles or inguinal region. 34 patients received rehabilitation therapy for 8 - 12 weeks under the support of factor replacement, complete hematomas absorption in 33 of them, with hip range of motion recovering back to baseline. 27 of 32 (84.4%) cases with femoral nerve injury got quadriceps strength above 4/5 grade, 20 cases of femoral nerve injury (62.5%) still had numbness on front of their thigh after treatment.

CONCLUSIONSIn this cohort of iliopsoas bleeding, most of the patients are adolescent. High prevalence of the femoral nerve injury and the secondary knee bleeding are found. Rehabilitation treatment under the support of factor replacement is safe and effective on hematoma absorption and neurological function recovery.

Adolescent ; Adult ; Child ; Hematoma ; etiology ; rehabilitation ; Hemophilia A ; complications ; rehabilitation ; Hemorrhage ; etiology ; rehabilitation ; Humans ; Male ; Middle Aged ; Muscular Diseases ; diagnosis ; etiology ; rehabilitation ; Psoas Muscles ; physiopathology ; Retrospective Studies ; Young Adult

PURPOSE: To evaluate the results of levator resection in patients with myopathic ptosis. METHODS: The medical records of consecutive patients who underwent levator resection surgery performed for myopathic ptosis between October 2009 and March 2013 were reviewed. Indications for surgery were ptosis obscuring the visual axis and margin-reflex distance < or =2 mm. Surgical success was defined as clear pupillary axis when the patient voluntarily opened his eye and margin-reflex distance > or =3 mm. We analyzed the effect of levator function and Bell's phenomenon on the rates of success and corneal complication. RESULTS: This series included six male and six female patients. Levator function was between 4 and 12 mm. We performed bilateral levator resection surgery in all patients. The mean follow-up time was 14.8 months (range, 6 to 36 months). No patient was overcorrected. Adequate lid elevation was achieved after the operation in 20 eyes. Ptosis recurred in three out of 20 eyes after adequate lid elevation was achieved. Our overall success rate was 70.8%. In three eyes with poor Bell's phenomenon, corneal irritation and punctate epitheliopathy that required artificial eye drops and ointments developed in the early postoperative period, although symptoms resolved completely within 2 months of the resection surgery. No patients required levator recession or any other revision surgery for lagophthalmos or corneal exposure after levator resection. CONCLUSIONS: Levator resection seems to be a safe and effective procedure in myopathic patients with moderate or good Bell's phenomenon and levator function greater than 5 mm.
Adult ; Aged ; Blepharoptosis/*surgery ; Blinking/physiology ; Female ; Humans ; Male ; Middle Aged ; Muscular Diseases/*surgery ; Oculomotor Muscles/*surgery ; *Ophthalmologic Surgical Procedures ; Postoperative Complications

Calcific myonecrosis is a rare late post-traumatic condition, in which a single muscle is replaced by a fusiform mass with central liquefaction and peripheral calcification. Compartment syndrome is suggested to be the underlying cause. The resulting mass may expand with time due to recurrent intralesional hemorrhage into the chronic calcified mass. A diagnosis may be difficult due to the long time between the original trauma and the symptoms of calcific myonecrosis. We encountered a 53-year-old male patient diagnosed with calcific myonecrosis in the lower leg. We report the case with a review of the relevant literature.
Calcinosis/*diagnosis/etiology/pathology ; Compartment Syndromes/complications ; Humans ; *Leg ; Male ; Middle Aged ; Muscle, Skeletal/pathology ; Muscular Diseases/*diagnosis/etiology/surgery ; Necrosis

Hypothyroidism can cause a variety of signs and symptoms of the neuromuscular system. However, ptosis in a patient with hypothyroidism is very rare. We report here on a case of central hypothyroidism that was due to Sheehan's syndrome and it manifested as bilateral ptosis in a 51-yr-old woman. She complained of exertional dyspnea and weakness. About 25-yr ago, she had a history of severe postpartum vaginal bleeding. The laboratory studies demonstrated hypopituitarism with secondary hypothyroidism. The ptosis was improved by replacement of thyroid hormone. Hypothyroidism should be considered in the differential diagnosis of patients who manifest with ptosis and that prompt replacement of hormone can lead to a complete recovery.
Blepharoptosis/complications/*diagnosis/drug therapy ; Electromyography ; Female ; Glucocorticoids/therapeutic use ; Humans ; Hypopituitarism/complications/*diagnosis/drug therapy ; Hypothyroidism/complications ; Magnetic Resonance Imaging ; Middle Aged ; Muscular Diseases/etiology ; Neuromuscular Junction/physiopathology ; Prednisolone/therapeutic use ; Thyroxine/therapeutic use

A 51-year old man presented with vertical and torsional diplopia after reduction of a blowout fracture at another hospital one year ago. He had no anormalies of head position and 14 prism diopters (PD) right hypertropia (RHT) in the primary position. In upgaze no vertical deviation was found, and hyperdeviation on downgaze was 35PD. Bielschowsky head tilt test showed a negative response. Distinct superior oblique (SO) and inferior rectus (IR) underaction of the right eye was noted but IO overaction was mild on the ocular version test. Double Maddox rod test (DMRT) revealed 10-degree extorsion, but fundus extorsion was minimal in the right eye.Thin-section coronal CT scan showed that there was no fracture line on the anterior orbital floor, but a fracture remained on the posterior orbital floor. Also, the anterior part of the right inferior oblique muscle was vertically reoriented and the medial portion of the inferior oblique muscle was not traced on the coronal CT scan. The patient underwent 14 mm right IO recession and 3 mm right IR resection. One month after the surgery, his vertical and torsional diplopia were eliminated in the primary position.
Constriction, Pathologic/complications/etiology/physiopathology/radiography ; Diplopia/etiology ; Humans ; Male ; Middle Aged ; Muscular Diseases/complications/etiology/*physiopathology/*radiography ; Oculomotor Muscles/*physiopathology/*radiography/surgery ; Orbital Fractures/*complications ; *Tomography, X-Ray Computed