Successful treatment of respiratory failure in Hirayama disease.

Hirayama disease is a self-limiting cervical motor neuron disease, usually affecting the spinal cord at level C7-T1. We share an unusual case of Hirayama disease in a young man affecting roots C4-C6. He presented in coma due to diaphragm weakness and hypercapnic respiratory failure. Diagnosis was achieved via clinical presentation, neurophysiological examination, ultrasonography of the diaphragm and dynamic MR-imaging. Conservative treatment with a cervical collar resulted in remarkable improvement in respiratory and motor function.

Anterior cervical discectomy and fusion for the treatment of pediatric Hirayama disease.

PURPOSE: Hirayama disease, a rare cervical myelopathy in children and young adults, leads to progressive upper limb weakness and muscle loss. Non-invasive external cervical orthosis has been shown to prevent further neurologic decline; however, this treatment modality has not been successful at restoring neurologic and motor function, especially in long standing cases with significant weakness. The pathophysiology remains not entirely understood, complicating standardized operative guidelines; however, some studies report favorable outcomes with internal fixation. We report a successful surgically treated case of pediatric Hirayama disease, supplemented by a systematic review and collation of reported cases in the literature. METHODS: A review of the literature was performed by searching PubMed, Embase, and Web of Science. Full-length articles were included if they reported clinical data regarding the treatment of at least one patient with Hirayama disease and the neurologic outcome of that treatment. Articles were excluded if they did not provide information on treatment outcomes, were abstract-only publications, or were published in languages other than English. RESULTS: Of the fifteen articles reviewed, 63 patients were described, with 59 undergoing surgery. This encompassed both anterior and posterior spinal procedures and 1 hand tendon transfer. Fifty-five patients, including one from our institution, showed improvement post-treatment. Eleven of these patients were under 18 years old. CONCLUSION: Hirayama disease is an infrequent yet impactful cervical myelopathy with limited high-quality evidence available for optimal treatment. The current literature supports surgical decompression and stabilization as promising interventions. However, comprehensive research is crucial for evolving diagnosis and treatment paradigms.

Laminoplasty with tented duraplasty for Hirayama disease.

BACKGROUND: Hirayama disease (HD) is a characterized by progressive amyotrophy of the upper limbs due to a forward displacement of the cervical dura during neck flexion. METHODS: Unlike other treatment options aiming at preventing cervical flexion (e.g., collar or arthrodesis), laminoplasty with tented duraplasty addresses dural dysplasia. Technically, the procedure consists in enlarging the dural sac by performing an expansile duraplasty that is secured to the yellow ligaments, in association with an open-book laminoplasty. CONCLUSION: Laminoplasty with tented duraplasty is a surgical option addressing the cause of HD to prevent further neurological deterioration while preserving cervical motion.

Hirayama's disease associated with cervical deformity and spinal cord compression: a case report from Sweden.

BACKGROUND: Hirayama's disease (HD) is most common in young males, and previous studies are predominantly from Asian countries. The cause of HD is unknown but the most common theory about the pathology speculates on forward bending that causes a compression of the dura mater and the anterior horn of the spinal cord against the vertebra during an overstretch flexion that may result in myelopathy. Both anterior and posterior cervical surgical approaches have been shown to be effective in stopping the disease and improving function; however, HD is also reported to be a self-limited disease, and treatment with a cervical collar may be an alternative for these patients. CASE REPORT: We report HD in a 17-year-old male from Sweden who underwent surgical treatment with a 2 level anterior cervical discectomy and fusion (ACDF) due to neurological progression from HD after conservative treatment. CONCLUSION: HD is rare and is easily overlooked. Surgical intervention shows promising results for neurological progression, but HD is also reported to be a self-limited disease.

Hirayama Disease: Surgical Restoration of Hand Function.

PURPOSE: Hirayama disease (HD) is a rare, nonfamilial, self-limiting, progressive lower cervical myelopathy, resulting in debilitating distal upper-extremity motor deficits, mimicking high ulnar neuropathy, lower trunk brachial plexopathy, or C8-T1 radiculopathy. Although most literature focuses on pathophysiology and prevention of disease progression, there remains limited discussion regarding treatment to improve upper-extremity function in patients with stable disease. The upper-extremity manifestations of HD are reviewed along with surgical options for restoring hand function. METHODS: A retrospective review of patients with HD who underwent reconstruction to improve hand function was undertaken. Demographic data, preoperative electrodiagnostic and electromyographic, and physical examination findings were collected. Outcome data involved postoperative grip, pinch, and functional assessment documented on clinical visits. Qualitative descriptions of the surgical techniques are described. RESULTS: Among six patients identified, four met the inclusion criteria and underwent tendon transfers and selected joint arthrodeses. All patients were diagnosed as teenagers, were right hand-dominant, and three were male. Unilateral symptoms were present in one patient and were bilateral in the rest. All patients were treated with tendon transfers for thumb opposition, grasp, anticlaw, and thumb interphalangeal joint arthrodesis. All patients had postoperative grip strength improvement. The average follow-up was 3.2 years. CONCLUSIONS: Hirayama disease is a rare disease often managed by spine surgeons and neurologists who may be unaware of options for restoring hand function deficits. Technical strategies and outcomes of improving hand function in HD have not been adequately described. Surgical options to improve hand function are tailored to the deficits and include tendon transfers, select joint arthrodeses, and/or tenodeses. Risk of disease progression and expectations following hand reconstruction must be managed carefully. TYPE OF STUDY LEVEL OF EVIDENCE: Therapeutic V.

Association of joint hypermobility with range of cervical motion and its impact on the motor unit loss in patients with Hirayama disease.

INTRODUCTION/AIMS: Some patients with Hirayama disease (HD) may have generalized joint hypermobility (GJH), which may excessively increase cervical range of motion (ROM) and then worsen the HD. The purpose of this study was to identify the frequency of GJH in HD patients and to analyze the effect of GJH on cervical ROM and the severity of HD. METHODS: The Beighton scoring system (≥4) was used to diagnose GJH in 84 HD patients. All patients underwent assessments of cervical-flexion/extension ROM; motor unit number estimation in bilateral abductor pollicis brevis (APB) muscles; handgrip strength; and the disabilities of the arm, shoulder, and hand assessments. RESULTS: Concomitant GJH was identified in 20 (23.8%) HD patients. The HD patients with GJH exhibited greater cervical-flexion (P < .001) and cervical-extension (P = .033) ROM than those without GJH. Both greater single motor unit potential amplitudes (symptomatic side: P = .005; less-symptomatic side: P = .011) and lower motor unit numbers (symptomatic side: P = .008; less-symptomatic side: P = .013) in bilateral APB, along with lower compound muscle action potential amplitudes on the symptomatic-side APB (P = .039), were observed in patients with GJH than those without GJH. There was a mild negative correlation between motor unit number and cervical-flexion ROM in HD patients (symptomatic side: r = -0.239, P = .028; less-symptomatic side: r = -0.242, P = .027). DISCUSSION: The frequency of GJH in HD patients may be higher than in the general population. Importantly, GJH may exacerbate excessive cervical-flexion ROM, thereby worsening motor unit loss in HD patients. A cautious approach should be taken when treating HD due to possible comorbid GJH.

Loss of cervical sagittal alignment worsens the cervical spinal lesions in patients with Hirayama disease.

OBJECTIVE: To quantify the cervical sagittal alignment in patients with Hirayama disease (HD) and to investigate the effect of loss of cervical sagittal alignment upon the cervical spinal lesions in HD. METHODS: Cervical sagittal alignments were measured in 253 HD patients and 63 healthy subjects by C2-C7 Cobb and a modified method of Toyama et al. Motor unit number estimation (MUNE) was performed in bilateral abductor pollicis brevis (APB) in all HD patients, and 31 patients further underwent cervical diffusion tensor imaging (DTI). RESULTS: Compared with healthy subjects, HD patients showed lower C2-C7 Cobb (P < 0.05), and 83.4% patients showed loss of cervical lordosis (cervical straight or kyphosis), which was greater than healthy subjects (55.6%, P < 0.05). Compared with lordotic/straight group, patients with cervical kyphosis showed lower MUNE values and greater single motor unit potential (SMUP) in bilateral APB, and higher apparent dispersion coefficient (ADC) and lower fractional anisotropy were observed at C4/C5 level in the latter than the former (P < 0.05). C2-C7 Cobb was associated with both C4/C5 ADC and bilateral SMUP (P < 0.05). CONCLUSIONS: Most HD patients showed loss of cervical sagittal alignments, and both MUNE and DTI detections demonstrated a positive correlation between loss of cervical sagittal alignments and cervical spinal lesions in HD. These findings supported that loss of cervical sagittal alignments may worsen motor impairments in HD. Therefore, it is necessary for clinicians to be aware of restoring cervical sagittal alignments during HD treatment.

The role of leisure-time physical activity in maintaining cervical lordosis after anterior cervical fusion and its impact on the motor function in patients with hirayama disease: a retrospective cohort analysis.

BACKGROUND: Surgical treatment has been increasingly performed in Hirayama disease (HD) patients to limit excessive neck flexion and restore cervical lordosis. However, postoperative recurrence of cervical lordosis loss may restart the progress of HD. Many studies have demonstrated a relationship between neck muscle strength and cervical lordosis, and it is widely accepted that leisure-time physical activity (LTPA) can increase muscle strength. However, there are few reports about the correlation between LTPA and maintenance of postoperative cervical curvature. OBJECTIVE: To quantify the cervical lordosis and motor function before and after operation in HD patients and to analyze the impact of postoperative LTPA levels on the changes in these measurements. METHODS: C2-7 Cobb were measured in 91 HD patients before, 2-5 days and approximately 2 years after operation. Motor unit number estimation (MUNE) and handgrip strength (HGS) were performed in all patients before and approximately 2 years after operation, and both cross-sectional area and fatty infiltration of posterior cervical muscles were measured in 62 patients. Long-form international Physical Activity Questionnaire and its different domains was administered to all patients at postoperative 2-year assessments. RESULTS: The C2-7 Cobb was larger immediately and approximately 2 years after operation than that at preoperative assessment (P < 0.05). The preoperative to postoperative change in C2-7 Cobb was associated with postoperative changes in the symptomatic-side HGS and bilateral MUNE measurements (P < 0.05). Importantly, the patients performing LTPA had greater improvements in C2-7 Cobb from immediate to approximately 2 years after operation and greater C2-7 Cobb at last follow-up than those without LTPA, and postoperative improvements in both symptomatic-side MUNE measurements and symptomatic-side HGS were also greater in the former than in the latter (P < 0.05). CONCLUSIONS: Postoperative LTPA has a positive effect on recovery/maintenance of cervical lordosis after operation, which may alleviate the motor unit loss of distal upper limbs in HD patients. Therefore, postoperative LTPA may be beneficial for postoperative rehabilitation or early conservative treatment of HD patients.

Outcome of Tendon Transfer for Monomelic Amyotrophy (Hirayama Disease).

Hirayama disease is a motor neuron disease predominantly affecting adolescent males. The identifying feature of Hirayama disease is unilateral forearm and intrinsic muscle weakness that spares the brachioradialis, termed "oblique atrophy." Hirayama disease progresses slowly over several years, followed by an abrupt arrest. The pathognomonic finding is the anterior displacement of the cervical spinal cord with the detachment of the posterior dura. Systematic clinical evaluation and appropriate diagnostic studies are crucial to rule out a variety of compressive, immune-mediated, and genetic disorders. We present a patient with Hirayama disease whose hand function was improved dramatically by a tendon transfer after nearly 3 years without a definitive diagnosis and call attention to the hand surgeon's role in identifying this rare disease to enable timely functional restoration.

Hirayama disease: neutral and flexion magnetic resonance imaging and utility of inter-segmental angle of flexion.

Purpose: Hirayama disease (HD) is a rare disease that was commonly mis-diagnosed in the past. The importance of neutral and flexion magnetic resonance imaging (MRI) in its accurate diagnosis has been emphasized along with utility of the inter-segmental angle of flexion. Aim of the study was to observe MRI findings of HD in neutral and flexion position and measure the inter-segmental angle of flexion. Material and methods: Cervical MR images of 17 patients of suspected HD were evaluated retrospectively for loss of attachment (LOA) of posterior dura, lower cervical cord atrophy, T2 hyperintensity, loss of cervical lordosis, enhancement of posterior epidural venous plexus, and inter-segmental angle of flexion on neutral and flexion MRIs. Results: Flexion MRI showed LOA of posterior dura (most commonly and maximum at C6 vertebral level) and intense enhancement in posterior epidural space in almost all patients. The mean inter-segmental angle of flexion at C5-C6 was 9.2°, and at C6-C7 it was 6°. Neutral MRI revealed LOA in 64.7%, lower cervical cord atrophy in all patients, T2 hyperintensity in the lower cervical cord in 35.2% of patients, and loss of cervical lordosis in 58.8% of patients. Conclusions: Flexion MRI is the gold standard for diagnosis of HD; however, certain imaging attributes, i.e. loss of attachment of posterior dura, asymmetrical lower cervical cord atrophy, T2 hyperintensity, and loss of cervical lordosis, can be seen on neutral MRI as well, which subsequently prompts the radiologist to include flexion MRI for confirmation. The inter-segmental angle of flexion is increased in patients with HD, which plays a role in planning timely surgical intervention.

Impact of various cervical surgical interventions in patients with Hirayama's disease-a narrative review and meta-analysis.

Hirayama disease (HD) is a relatively uncommon cause of lower cervical myelopathy. A number of surgical approaches have been described in patients with HD in literature. We reviewed the literature and did a systematic review and meta-analysis of the studies which presented the clinical outcome following surgical intervention in HD. A systematic search of literature was performed with the keywords "Surgical treatment in Hirayama Disease", "Surgical approach in Hirayama Disease" and "Hirayama disease surgery". Data related to clinical outcome following surgery was pooled to calculate the pooled proportion of clinical improvement following anterior and posterior surgical approach. Thirty-four articles met the inclusion criteria and were included in the final review. Altogether, there were 10 types of surgical procedures performed for Hirayama disease. The most commonly described surgical technique was anterior cervical discectomy and fusion with cervical plating. The pooled proportion of patients experiencing clinical improvement following all cervical approaches was 80% (95% confidence interval 76 to 84%). Pooled proportion was maximum for anterior cervical plating (96% (95% confidence interval 62 to 100%)) and minimum for ACDF without plating (57% (95% confidence interval 20 to 88%)). Subgroup analysis based on different surgical approaches was not significant (p value = 0.61). The pooled proportion of patients experiencing clinical improvement following anterior and posterior cervical approach was 80% (95% confidence interval 76 to 84%) and 81% (95% confidence interval 66 to 91%). The indications of surgical treatment in patients with HD include poor patient compliance for neck collar or rapidly progressing severe disease. Good results with more than 80% chances of clinical improvement have been reported following various anterior and posterior surgical approaches. However, there was no significant difference in the pooled outcome of different surgical approaches. Most common technique used in literature is anterior cervical discectomy and fusion with plating.

Hirayama Disease in a Patient with a History of Late-Onset Symptomatic Vein of Galen Aneurysmal Malformation.

INTRODUCTION: The purpose of this report is to present a rare case of Hirayama disease (HD) in a patient with a history of late-onset symptomatic vein of Galen aneurysmal malformation (VGAM). This report may provide new insights into the pathophysiology of HD, a rare disorder consisting of insidious onset of unilateral weakness and atrophy of the forearm and intrinsic hand muscles. These symptoms are believed to result from cervical myelopathy affecting the anterior horn cells due to abnormal compressive forces on the spinal cord from adjacent anatomical structures (i.e., dura and/or epidural veins), but this has not been proven. VGAM is a rare congenital cerebral vascular malformation, consisting of high-flow arteriovenous shunting between a persistent median prosencephalic vein and arterial feeders, which most frequently presents in the early neonatal period with congestive heart failure. CASE PRESENTATION: We report the case of an otherwise healthy boy who presented with heart failure due to VGAM at 7 years and subsequently presented at 14 years with left-sided HD. His cervical MRI with neck flexion revealed enlarged epidural veins at the C5-C6 spinal level with anterior, leftward displacement of the posterior dura and spinal cord as well as left hemicord flattening and/or atrophy at this level. He underwent successful surgical treatment by C5-C6-C7 osteoplastic laminotomies and tenting and expansile autologous duraplasty, during which enlarged, engorged epidural veins were confirmed and coagulated. This halted the progression of his left hand weakness and atrophy and allowed significant functional improvement. Postoperative catheter angiogram showed no anatomical connection between the persistent VGAM and the engorged epidural veins, and genetic testing revealed no genetic predisposition of vascular malformations. DISCUSSION/CONCLUSION: In this patient, a combined surgical technique was performed that included epidural venous plexus coagulation with posterior autologous duraplasty and dural fixation using tenting sutures. This combined approach led to a favorable clinical and radiographic outcome with no complications or limitations and has not been previously proposed in the literature, to our knowledge. Although not completely ruled out, we found no angiographic connection or genetic predisposition to suggest there is a pathophysiological link between HD and VGAM.

Polymyoclonus aggravated by neck flexion as the isolated presenting symptom of Hirayama disease: case report.

BACKGROUND: We report a rare case of an 18-year-old male with unilateral hand tremor who was finally diagnosed with Hirayama disease (HD). CASE PRESENTATION: An 18-year-old male presented with unilateral polymyoclonus that aggravated with neck flexion. The patient did not complain of muscle weakness or muscle atrophy. The needle electromyography showed giant motor unit potentials in right cervical 7 and 8 innervated muscles. The cervical magnetic resonance imaging on supine and flexion state showed prominent forward effacement of posterior dural sac that was compatible with HD. CONCLUSIONS: HD usually presents with unilateral distal hand weakness, muscle atrophy and tremor. Although it is a benign and self-limiting disease, early diagnosis may lead to less clinical deterioration. Moreover, electromyography should be completed in the differentiation of young male patients who present with polymyoclonus without hand weakness or atrophy.

Is there cervical spine muscle weakness in patients with Hirayama disease? A morphological study about cross-sectional areas of muscles on MRI.

PURPOSE: Patients with Hirayama disease (HD) present with a larger range of neck flexion and show signs of cervical spine instability. Cervical spine stability largely relies on cervical spine muscles. The purpose of this study was to compare the cross-sectional areas (CSAs) of cervical spine muscles between patients with HD and healthy controls, providing some insights into whether there is cervical spine muscle weakness and incongruence in HD patients. METHODS: In this retrospective study, cervical spine muscles CSAs of 44 HD patients, as well as that of 44 age- and sex-matched healthy counterparts, were measured on the T2-weighted axial MR images. The ratios of cervical spine muscles CSA to the corresponding vertebral body areas, defined as R-CSAs, and the flexor/extensor CSA ratios were computed and compared between two groups. RESULTS: Compared with healthy counterparts, R-CSAs of total cervical spine muscles, total extensors, superficial extensors, and deep flexors were significantly lower in HD patients. HD patients also demonstrated a significantly greater superficial flexor/superficial extensor CSA ratio than the healthy counterparts, indicating a mismatch between superficial flexors CSA and superficial extensors CSA in HD patients. CONCLUSIONS: In this pioneering study, HD patients had decreased size in most cervical spine muscles and a mismatch between CSAs of superficial flexor and that of superficial extensors. These results indicate generalized weakness and incongruence of cervical spine muscles, which may predispose cervical spine of HD patients to a less stable situation. These slides can be retrieved under Electronic Supplementary Material.

Hirayama disease: analysis of cases in Russia.

The fourteen cases of Hirayama disease (HD) are presented in this article. HD is seldom disease characterized by juvenile muscular atrophy of upper extremities and benign course. All cases were diagnosed in the Research Center of Neurology (Moscow, Russia) during the year 2015-2017. Such methods as MRI (magnetic resonance imaging), EMG (electromyography), and NCS (nerve conduction studies) have been used to confirm diagnosis of HD. Transcranial magnetic stimulation was used to exclude upper motor neuron involvement in two cases. The original scale of neurological disturbances in HD has been proposed by authors to reveal correlations of HD severity with age of patients and duration of disease.Most of patients with HD are young males with common clinical signs. Detected MRI and EMG data were also comparable with previous publications. Independence of HD severity from age and duration of the disease may be the result of individual physical characteristics of dura mater and other structures of the cervical vertebra. In some our cases, amyotrophic lateral sclerosis and other neurological disorders were misdiagnosed before. In view of different prognosis in these pathologies and possible correction of HD, early diagnosis is very important.

The evaluation on neural status of cervical spinal cord in normal and Hirayama disease using diffusion tensor imaging.

PURPOSE: To explore the changes in diffusion tensor imaging (DTI) parameters in cervical spinal cord in Hirayama disease (HD) patients and healthy volunteers and to compare these parameters between cervical flexion and neutral positions in HD patients. METHODS: Seventeen male patients with HD and eleven healthy young males were included to receive DTI scans in cervical flexion and neutral positions. The FA and ADC values of different levels were measured based on the region of interest drawn on the mid-sagittal plane. The dynamic compressed level's parameters were defined as the lowest and the second lowest FA and the highest and the second highest ADC, respectively. The clinical assessment of patients was obtained using their disabilities of the arm, shoulder and hand (DASH) scores. RESULTS: For the HD patients, the FA values in the cervical flexion position were lower and the ADC values were much higher than those in the cervical neutral position. Compared with the controls, the ADC values were significantly higher in the lower levels (C5/6-C7/T1) and the FA values obviously lower at C7/T1 in HD patients in cervical neutral position. The FA and ADC values of the dynamic compressed level in HD patients deviated significantly from the average of the lower levels in controls. Both the FA and ADC values of the dynamic compressed level correlated with the DASH scores (FA, R2 = 0.520, P = 0.001; ADC, R2 = 0.421, P = 0.005). CONCLUSIONS: DTI parameters can support a hypothesis of dynamic cervical flexion compression and noninvasively reveal the neural status of HD patients. These slides can be retrieved under Electronic Supplementary Material.

Hirayama disease/cervical flexion-induced myelopathy progressing to spastic paraparesis: A report on three cases with literature review.

Hirayama disease (HD)/cervical flexion-induced myelopathy (CFIM) is a lower motor neuron disease conventionally affecting a single upper extremity. We describe three men progressing after a long stable period to develop severe spastic paraparesis and bladder disturbances as a protracted implication of HD. The age at onset was 20, 24, and 15 years, while the age at presentation was 27, 41, and 57 years, respectively. The second phase of disease progression occurred after 4, 13, and 28 years of stationary period. All had CFIM with characteristic magnetic resonance imaging features as observed during progressive stages. The anterior dural shift extended variably from C4 to D4 levels with a median value of 5 mm and was maximum at C6 to C7 levels, pushing the cord anteriorly causing compression. This study emphasizes the need to recognize this unusual subgroup of HD and mandates long-term follow-up with timely intervention in arresting the progression/improving the deficits.

Atypical type of Hirayama disease: Onset of proximal upper extremity.

Hirayama disease is a rare, benign motor neuron disease. It has been proposed that the dura mater's posterior wall lacks sufficient elasticity in the lower cervical region and this causes the tense dura part to displace anteriorly upon flexion. The disease is described as involving unilateral upper extremity with a distal-onset. We reported weakness and atrophy of the proximal part of an extremity in a 45-year-old man who is diagnosed with Hirayama disease. Proximal onset is a rare type of Hirayama Disease. Clinicians must be alert of proximal involvement and the diagnosis should be confirmed with electrophysiological and flexion MRI studies.

Benign focal amyotrophy.

Within lower motor neuron diseases, benign focal amyotrophy is a rare syndrome characterized by insidious neurogenic asymmetric atrophy restricted to upper or lower limbs with a good prognosis over time. Described under several terms, the nosology is probably heterogeneous. In juvenile distal upper-limbs forms, specific MRI signs with in particular a compression of the spinal cord by forward displacement of dura, lead to evoke a mechanical process. In other forms, occurring later in the life, affecting proximal part of upper limbs or lower limbs, the physiopathology is still unknown and a focal spinal muscular atrophy is suspected. In this review, we will discuss the clinical, electrophysiological and radiological features of each presentation.

Juvenile muscular atrophy of the distal upper extremities associated with x-linked periventricular heterotopia with features of Ehlers-Danlos syndrome.

INTRODUCTION: Juvenile muscular atrophy of the distal upper extremities (JMADUE) is a rare, sporadic disorder that affects adolescent males and is characterized by progressive but self-limited weakness of the distal upper extremities. The etiology is unknown, but cervical hyperflexion has been hypothesized. METHODS: We report a case of an adolescent male who presented with typical JMADUE but also had joint hypermobility and multiple congenital anomalies, including periventricular heterotopias, suggesting a multisystem syndrome. RESULTS: Subsequent diagnostic testing confirmed a diagnosis of JMADUE, and sequencing of the filamin-A gene showed a novel, pathogenic mutation that confirmed an additional diagnosis of X-linked periventricular heterotopias with features of Ehlers-Danlos syndrome (XLPH-EDS). CONCLUSIONS: The concurrent diagnosis of these 2 rare conditions suggests a pathogenic connection. It is likely that the joint hypermobility from XLPH-EDS predisposed this patient to developing JMADUE. This supports the cervical hyperflexion theory of pathogenesis. This case also expands the phenotype associated with FLNA mutations. Muscle Nerve 54: 794-797, 2016.