Family History Of Similar Symptoms Research Articles

Clinical diagnosis and management of spinocerebellar Ataxia in a resource-constrained setting: a case report from Eastern Nepal

Introduction: Spinocerebellar ataxias (SCA) are a diverse group of neurodegenerative disorders with autosomal dominant inheritance, primarily affecting the cerebellum and its connections. Diagnosis typically involves genetic testing, but in resource-limited settings, clinical and neuroimaging assessments become critical. This case report highlights the role of non-genetic methods in diagnosing SCA and outlines management strategies in such settings. Case Presentation: A 41-year-old male presented with a two-year history of progressive gait imbalance, headache, and abnormal speech. He had a family history of similar symptoms in two siblings, but no significant past medical history. Clinical examination revealed scanning speech, dysmetria, and a broad-based gait. Clinical and neuroimaging findings, including cerebellar atrophy, led to a diagnosis of SCA in the absence of genetic testing. Patient management with speech, occupational, and physical therapies, showed gradual improvement. Discussion: SCA, characterized by cerebellar atrophy and a range of clinical symptoms, is typically diagnosed through genetic testing, but clinical and imaging assessments are crucial when genetic resources are limited. This case illustrates that a comprehensive clinical evaluation, including neuroimaging, can support the diagnosis of SCA even without genetic testing. Strategic management emphasizing symptomatic relief and functional improvement through a multidisciplinary approach, including regular follow-up and personalized therapy, are crucial, as evidenced by the timely improvement observed in our case. Conclusion: In resource-limited settings, a comprehensive clinical and neuroimaging assessment is essential for diagnosing Spinocerebellar Ataxia when genetic testing is not feasible. Effective management through multidisciplinary therapies can improve patient outcomes, underscoring the need for innovative strategies to enhance diagnostic and treatment capabilities in such environments.

Novel SGCE Mutation in a Patient With Myoclonus-Dystonia: A Case Report.

Characterize the presentation, workup, and management of SGCE myoclonus-dystonia, a rare genetic condition, in a patient with atypical presenting symptoms and no family history of movement abnormalities. A woman with myoclonus and dystonia was identified based on clinical history and physical examination. Workup was conducted to determine the cause of her symptoms, including whole-exome sequencing. Myoclonus-dystonia is associated with more than 100 distinct mutations in MYC/DYT-SGCE that account for only half of the total myoclonus-dystonia patients. As such, this case required intensive genetic analyses rather than screening only for a small subset of well-characterized mutations. Childhood onset myoclonus and worsening dystonia with age were identified in a young woman. She underwent screening for common causes of twitching movements, followed by whole-exome sequencing which identified a de novo novel variant in the SGCE gene, resulting in a diagnosis of SGCE myoclonus-dystonia. Myoclonus-dystonia should be considered in patients with symptoms of head and upper extremity myoclonus early in life, especially with co-occurring dystonia, even in the absence of a family history of similar symptoms. Diagnosis of this condition should take place using sequencing, as new mutations continue to be discovered.

Genetic Myelopathies.

This article provides an overview of genetic myelopathies, a diverse group of inherited, degenerative conditions that may be broadly categorized as motor neuron disorders, disorders of spinocerebellar degeneration, leukodystrophies, and hereditary spastic paraplegia. Clinical examples from each category are provided to illustrate the spectrum of genetic myelopathies and their distinguishing features that aid in differentiating genetic myelopathies from potentially treatable acquired causes of myelopathy. Advances in genetic testing have vastly enhanced current knowledge of genetic myelopathies and the ability to diagnose and provide appropriate counseling to patients and their families. However, potential health care disparities in access to genetic testing is a topic that must be further explored. Although treatment for most of these conditions is typically supportive, there have been recent therapeutic breakthroughs in treatments for amyotrophic lateral sclerosis, spinal muscular atrophy, and Friedreich ataxia. Genetic myelopathies may present with chronic and progressive symptoms, a family history of similar symptoms, and involvement of other structures outside of the spinal cord. Imaging often shows spinal cord atrophy, but cord signal change is rare. Exclusion of reversible causes of myelopathy is a key step in the diagnosis. There are many different causes of genetic myelopathies, and in some cases, symptoms may overlap, which underscores the utility of genetic testing in confirming the precise underlying neurologic condition.

Pediatric Charcot-Marie-Tooth disease: A case report and diagnostic challenges

Charcot-Marie-Tooth (CMT) disease is a hereditary motor sensory neuropathy affecting about one in 2500 individuals that is characterized by progressive weakness and loss of touch sensation affecting different parts of the body. Despite its significant genetic heterogeneity, CMT is rarely reported in the Indian literature. We report a 10-year-old boy with CMT presented with severe calf pain, bilateral pes cavus deformity, and areflexia. His mother also had similar symptoms, and the diagnosis was confirmed by neuroimaging and nerve conduction studies. This highlights the importance of considering CMT disease in patients with progressive muscle weakness and deformities, especially with a family history of similar symptoms.

The phenotype and genotype of Chinese adult patients with NLRP3-associated autoinflammatory disease.

NLRP3-associated autoinflammatory disease (NLRP3-AID) is a spectrum of autosomal dominant inherited diseases associated with NLRP3 gene mutations. Reports of Chinese NLRP3-AID cases are limited to date. In the present study, we aim to describe the phenotype and genotype of a cohort of Chinese adult NLRP3-AID patients METHODS: This single-center study included sixteen adult patients diagnosed with NLRP3-AID at Department of Rheumatology, Peking Union Medical College Hospital from April 2015 to September 2021. Whole-exome sequencing using next-generation sequencing was performed in each patient. Clinical data and mutational information were compared with a European cohort. The median age of disease onset was 16 (0-46) years old, and adult-onset was observed in 4 patients (25%). The median time of diagnosis delay was 20 (0-39) years. Five patients (31.3%) had family history of similar symptoms. The most common clinical manifestations were recurrent fever (93.8%), arthralgia/arthritis (81.3%), skin rash (75%), myalgia (62.5%), and central nervous system manifestations (50%). Heterozygous NLRP3 variants detected in these patients were p.T348M (n = 4, 25%), Q703K, V70M, K129R, M116I, P38S, V442I, D303G, G326E, A439V, K829T, L632F and V198M (n = 1, separately). All the variants were missense mutations. We reported the largest case series of Chinese adult NLRP3-AID patients. The distinct symptoms of NLRP3-AID patients suggest the heterogeneity of disease. P38S, M116I, K129R, V442I and K829T were identified as novel NLRP3 variants. These data expand the clinical phenotypic and genotypic profiles of NLRP3-AID. Key Points • We characterized the clinical and genetic features of sixteen Chinese adult NLRP3-AID patients. • Thirteen NLRP3 gene variants were confirmed in this cohort, and P38S, M116I, K129R, V442I and K829T were identified as novel variants. • Clinical data and mutation information were compared with a European cohort. • We hope these data would expand the phenotypic and genotypic profile of NLRP3-AID and raise the awareness of early diagnosis and accurate treatment among rheumatologists.

Clinical and Electrophysiological Presentation of a Patient with Multisystem Proteinopathy Associated with Valosin-Containing Protein Mutation (P5-8.005)

<h3>Objective:</h3> Present a rare case of multisystem proteinopathy (MSP) of apparently unrelated multisystem conditions caused by mutation in valosin-containing protein (VCP). <h3>Background:</h3> Multisystem proteinopathy (MSP) is a dominantly inherited disorder causing bone, muscle, central and peripheral nervous systems disease. Mutations within the gene encoding valosin-containing protein (VCP) cause MSP. Such mutations present with a vast phenotypical variability and are associated with inclusion body myopathy, Paget’s disease of bone, frontotemporal dementia, and amyotrophic lateral sclerosis. We present a case of MSP caused by c.464G&gt;A, p. arg155his mutation in VCP. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 65-year-old woman presented with proximal muscle weakness and unsteady gait. The symptoms started four years ago when she experienced progressive weakness of the upper and lower extremities leading to recurrent falls. She has no family history of similar symptoms or genetic disease. Examination revealed dropped head, scapular winging, inability to raise the arms above her shoulders, hand weakness, and bilateral foot drop. Her gait was unsteady with a mix of waddling and steppage. Creatine kinase and alkaline phosphatase levels were normal. MRI of spine revealed mild degenerative disc disease from C4–C7 and disc bulges at L3–L4 through L5–S1. The nerve conduction studies showed mixed myopathic and neurogenic changes with ongoing denervation in cervical and lumbar segments suggestive of motor neuronopathy. Genetic testing was remarkable for a heterozygous pathogenic mutation in VCP (c.464G&gt;A, p. arg155his). <h3>Conclusions:</h3> This case highlights the need to consider MSP in patients with a complex neurological presentation and combined myopathic and neurogenic electrodiagnostic findings. The absence of MSP-related symptoms in the patient’s family may indicate the variable severity associated with the same VCP mutation, interaction with environmental factors as well as presence of genetic modifiers.. <b>Disclosure:</b> Mr. Halber has nothing to disclose. Sabrina Bulancea has nothing to disclose. Dr. Treidler has nothing to disclose.

Recurrent hemorrhagic bullae of the oral mucosa

Recurrent hemorrhagic bullae of the oral mucosa

Sifrim-Hitz-Weiss/CHD4-related syndrome: A new case report.

Sifrim-Hitz-Weiss/CHD4-related syndrome: A new case report.

258 A case of two brothers: should we look beyond a diagnosis of cerebral palsy?

BackgroundPelizaeus-Merzbacher Disease (PMD) is an X-linked leukodystrophy with variable phenotypes often overlapping with cerebral palsy (CP).Case DescriptionsWe describe 2 brothers, presenting at the same time.Case1: 34 years old with a 2-year history of hand tremor, cognitive decline and deteriorating mobility. He required neonatal ICU following a prolonged delivery, was slow to walk and subsequently misdiagnosed at age 4. Examination revealed a left torticollis, intention tremor and spastic paraparesis.Case 2: 29 years old with progressive hand tremor and cognitive decline. He had nystagmus, titubation and late crawling and was diagnosed with CP within his first year of life; becoming wheelchair-bound by age 9. Examination revealed titubation, action tremor, nystagmus and spastic quadriparesis.There were no other family history of similar symptoms or genetic disorder prior to their births.Results of InvestigationsMRI Brain suggested leukodystrophy in both cases. Genetic analysis revealed pathogenic mutation in the PLP1 gene(c454–322G&gt;A;P?) confiriming a diagnosis of Pelizaeus Merzbacher Disease.ConclusionThe phenotypic similarities between PMD and CP especially in early childhood and the delayed progression of symptoms contributed to their misdiagnosis. We should look beyond Cerebral Palsy and consider PLP-related diseases in males with cerebral-palsy-like features regardless of a lack of family history.ihedinachindukwe@gmail.com

Low vision management in heredomacular degeneration: a case report

&lt;p class="abstract"&gt;Low vision devices are used to improve the visual performance of patient with low vision, hence allowing them to carry out their daily activities. The objective was to provide best low vision correct to a patient with heredomacular degeneration. A 10 year old girl came to our OPD in September 2015. The patient had history of reduced vision in both eyes since, 1 year. She was now unable to distinguish writing on the school blackboard. Her mother had observed over the last 6 months that she held reading matter very close to his face. Her mother also reported that she preferred to study in dim illumination. The patient had no known precipitating factor and no family history of similar symptoms. The patient had history of using glasses. The patient was diagnosed to have adult onset heredomacular degeneration and explained that the visual prognosis is guarded. In view of no definite treatment for this condition, the patient was prescribed spectacles. Heredomacular degenerations tend to be progressive and a long-term follow up is required.&lt;/p&gt;

EARLY SECONDARY SPONTANEOUS PNEUMOTHORAX IN A CAUCASIAN FEMALE WITH PAST PRIMARY SPONTANEOUS PNEUMOTHORAX

TOPIC: Lung Pathology TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pneumothorax is the trapping of air between the visceral and parietal pleura of the lungs.it is a well-established condition associated with smoking, vaping, Marfans syndrome, tall build and familial diseases like alpha 1 antitrypsin deficiency. CASE PRESENTATION: 45 y/o Caucasian lady who presented to the ER with sudden left sided pleuritic chest pain and Shortness of breath She denied palpitations, nausea or vomiting Past medical history was significant for right spontaneous pneumothorax for which she Video-assisted thoracoscopic surgery at the age of 31 and COPD She has smoked about 1.5 packs per day for over 20 years, 3-year history of vaping.She had no family history of similar symptoms On presentation, Her vitals were unremarkable except for O2 Saturation of 92 on room air which increased to 98 with 2L of O2Physical examination was remarkable for a tall, slender appearing lady with diminished breath sounds on the left lung base. Her laboratory investigations were unremarkable including troponin and EKG. Chest Xray showed bullous changes bilaterally with compressive atelectasis in both lungs with 20% left-sided pneumothorax, follow up CT scan of the chest showed Severe lung parenchymal disease with multiple cystic spaces all over the lungs and approximately 40% left-sided pneumothorax. Cardio-thoracic surgery was consulted following which she had Pig tail catheter inserted and connected to an underwater seal, however her pneumothorax was not resolving hence she had thoracotomy with blebectomy. Lung biopsy showed severe bullous emphysema with blebs, chronic inflammation, perilesional fibrosis and dystrophic calcificationPatient was strongly advised against smoking and she was scheduled to follow up in pulmonology clinic to rule out alpha 1 anti-trypsin deficiency, results of which were pending DISCUSSION: Secondary Spontaneous Pneumothorax is defined as pneumothorax that occurs in the presence of lung disease as with this patient who had underlying bullous disease.It is commonly found in male patients with an age preponderance of greater than 55 years, our patient however is a lady and less than 50 years Primary Spontaneous pneumothorax is pneumothorax occurring in the absence of lung disease. It is commonly found in males usually between ages 10-30 years It is very likely our patient initially had a primary spontaneous pneumothorax given her slender tall build which then progressed to secondary pneumothorax given her significant smoking, vaping history and severe bullous lung disease raising suspicious for underlying Alpha 1 antitrypsin deficiency. CONCLUSIONS: It is important to investigate further for individuals like this who present which such severe lung disease with unusual demographics REFERENCE #1: 1. Gupta D, Hansell A, Nichols T, Duong T, Ayres JG, Strachan D. Epidemiology of pneumothorax in England. Thorax. 2000 Aug;55(8):666-71. doi: 10.1136/thorax.55.8.666. PMID: 10899243; PMCID: PMC1745823. REFERENCE #2: Melton LJ 3rd, Hepper NG, Offord KP. Influence of height on the risk of spontaneous pneumothorax. Mayo Clin Proc. 1981 Nov;56(11):678-82. PMID: 7300447 DISCLOSURES: No relevant relationships by Karishma Kadariya, source=Web Response No relevant relationships by Evans Kyei-Nimako, source=Admin input No relevant relationships by Utibe Ndebbio, source=Web Response No relevant relationships by Demilade Soji-Ayoade, source=Web Response

When Your Thyroid Causes Muscle Paralysis

Background: Periodic paralysis represents a spectrum of disorders characterized by ion channel dysfunction, mainly Na-K-ATPase channels. Thyrotoxic periodic paralysis (TTP) is defined by the presence of hypokalemia and diffuse muscular paralysis in a pre-existing hyperthyroid state. Diagnosis can be challenging, especially in cases of undiagnosed hyperthyroidism due to the non-specific presentation of this illness. We present a case of a young male who presented with recurrent, spontaneous paralysis found to have Graves’ disease. Clinical Case: A 38-year-old Asian male presented with sudden onset diffuse weakness, numbness, and tingling. The weakness was so severe that he could barely walk more than a few steps. However, his symptoms resolved in less than 24 hours without any intervention. Five months later, the patient experienced a recurrent episode of this similar constellation of diffuse muscle weakness and paresthesia. The patient was taken to a nearby hospital, where he was provided with intravenous fluid resuscitation. Initial laboratory workup was notable for hypokalemia to 1.4 mmol/L (n: 3.6 - 5.3 mmol/L), hypophosphatemia to 0.6 mmol/L (n: 2.4 – 4.8 mmol/L), and elevated creatinine kinase to 807 U/L (n: 22 – 198 U/L). Additionally, TSH was <0.001 mU/L (n: 0.45 – 4.5 mU/L) along with free T4 3.4 ng/dL (n: 0.80 – 1.70 ng/dL. The patient denied any other symptoms or a family history of similar symptoms. Lumbar puncture and brain/spine MRIs were unremarkable. Symptoms gradually improved throughout hospitalization with fluid and electrolyte repletion. Hyperthyroidism was treated with methimazole 5mg twice daily, later changed to PTU 50mg every eight hours due to recurrent headaches. Thyroid uptake scan showed diffuse bilateral uptake to 39.11% at 4 hours and 61.8% at 24 hours. Follow up labs revealed: TSH 0.3 mU/L, free T4 1.44 ng/dL, free T3 3.5 pg/mL (n: 2.3 – 4.1 pg/mL). Patient denied recurrent episodes of weakness or paresthesia. Definitive hyperthyroidism treatment with RAI was planned. Conclusions: The prevalence of TPP is higher in Asian males compared to other ethnic groups. TPP manifests as a sporadic onset of muscle weakness ranging from mild weakness to flaccid paralysis. It has been described that thyroid hormone itself augments the activity of the Na-K-ATPase channel and increases its responsiveness to beta-adrenergic stimulation. In addition, hyperthyroidism is associated with insulin resistance leading to hyperinsulinemia. Both beta-agonism and insulin promote potassium to be driven into cells resulting in hypokalemia. As such, activities which increase beta adrenergic stimulation, like stress and exercise, and promote the secretion of insulin, such as heavy carbohydrate intake, are well described triggers of TPP. Treatment revolves around acutely treating hypokalemia followed by preventing subsequent attacks via regulation of the altered thyroid state.

AUTOPHAGIC MYOPATHIES / MYOFIBRILLAR MYOPATHIES / DISTAL MYOPATHIES / POMPE DISEASE: P.10 Distal myopathy associated with two novel variants in SPTAN1

The phenotypic spectrum associated with autosomal dominant SPTAN1 variants has evolved since the initial 2008 description of infantile epileptic encephalopathy due to non-truncating mutations. Loss of function variants were reported in association with a central nervous system phenotype without epilepsy in 2018, and with a juvenile onset hereditary motor neuropathy in 2019. Here we report novel SPTAN1 variants in two patients seen in our clinic. The first presented at 9 years old with a history of mild motor and cognitive delays, dysmorphic features and abnormal gait. Examination showed distal leg muscle atrophy and weakness most significant in the ankles. Serum CK was normal; limited EMG was unremarkable but showed no evidence for neuropathy. His family history was non-contributory, and standard genetic testing was non-diagnostic. Whole exome sequencing (WES) at age 11 identified a SPTAN1 variant (c.6657delC/p.Asn2220ThrfsTer44) that was not maternally inherited (father unavailable to test). The second presented to our clinic at age 15, with reported first symptoms of abnormal standing posture and delayed motor milestones noted at 20 months. Based on symptoms of bilateral distal atrophy, pes cavus and foot drop, he was thought to have a distal motor neuropathy. An EMG at age 15 years showed evidence of distal myopathy without evidence of neuropathy; serum CK was normal. There was no family history of similar symptoms, and genetic testing including MYH7 sequencing, FSHD testing and a neuromuscular gene panel, was all negative. Examination at age 22 showed distal weakness with preserved EDB bulk, and WES identified a de novo pathogenic truncating SPTAN1 variant (c.2613delG; p.Lys871AsnfsTer5). Additional follow-up studies (including more extensive EMG and muscle biopsy) are planned, and will be reported. These patients suggest that SPTAN1 variants may be associated with a distal myopathy, expanding the clinical heterogeneity associated with mutations in this gene.

Sporadic Hemiplegic Migraine with SCN1A Gene Mutation—A Case Report

Sporadic hemiplegic migraine (SHM) is a subtype of hemiplegic migraine, characterized by episodes of migraine with a reversible motor aura, without a positive family history, and is a mimicker of an atypical severe form of migraine, stroke, epilepsy, multiple sclerosis, metabolic disorders, or conversion disorder.Case presentation:We present the case of a young 28-year-old female, who had a history of recurrent reversible attacks of headache with sensory aura accompanied with left hemiparesis for the past 5 years, with no positive family history of similar symptoms. The work-up ruled out differential diagnoses and genetic work-up found a novelSCN1Agene missense variation in exon 26 (c.4855A&gt;G; p.Met1619Val) in a case of SHM. She was discharged on flunarizine for prophylaxis.Conclusions:We describe, for the first time, a case of SHM with a mutation in theSCN1Agene.

A rare hereditary disease: Muckle-Wells syndrome

Cryopyrin associated periodic syndrome (CAPS) is a dominantly-inherited autoinflammatory disease, which is included in the group of periodic fever syndromes. It is caused by a defect in the regulation of inflammatory cytokines, particularly interleukin-1β. CAPS encompasses a spectrum of three phenotypes of increasing severity: familial cold autoinflammatory syndrome, Muckle-Wells syndrome (MWS) and neonatal onset multisystem inflammatory disease. We report the case of a 58-year-old male, who had migratory joint pains, daily urticaria, chills, and episodic conjunctivitis since childhood and hearing loss in his 20s with a family history of similar symptoms. He was diagnosed with MWS after being found to have a &lt;em&gt;R262W&lt;/em&gt; gene mutation in &lt;em&gt;NLRP3&lt;/em&gt; gene and successfully treated with canakinumab. After his discovery, other 1&lt;sup&gt;st&lt;/sup&gt; and 2&lt;sup&gt;nd&lt;/sup&gt; degree family members with similar complaints were found to have the same genetic mutation and were also successfully treated with canakinumab.

Familial fatal insomnia with atypical clinical features in a patient with D178N mutation and homozygosity for Met at codon 129 of the prion protein gene

ABSTRACT. Familial fatal insomnia (FFI) is fatal disorder characterized by damage to select thalamic nuclei, together with progressive insomnia and dysautonomia. In subjects carrying the D178N prion protein (PRNP) mutation, distinct phenotypes can be observed, depending on the methionine (Met) /valine (Val) codon 129 polymorphism. We report here a Chinese case of FFI with a D178N/Met129 genotype of the PRNP gene, who exhibited rapidly progressive dementia combined with behavioral disturbances and paroxysmal limb myoclonus. Our patient did not show refractory insomnia early in the disease course, nor demonstrate typical MRI and EEG alterations. There was remarkable family history of similar symptoms.

Case Series of all three types of Ushers Syndrome of varying severity in the same family

Introduction: Ushers syndrome is an autosomal recessive disorder characterized by hearing loss and visual impairment due to retinitis pigmentosa. There are three types of Ushers syndrome with decreasing order of severity. Type 1 has onset of illness at birth with rapid progression of symptoms. Type 2 has gradual onset of symptoms with moderate hearing loss and later onset of night vision problems. Type 3 is the least severe form with onset of symptoms at late teenage. Case Series: We report here four siblings with Ushers. The first and second child had clinical symptoms suggestive of type1 Ushers. Third child has clinical features of Type 3 Ushers. Fourth child who had presented to us was having clinical features supportive of type 2 Ushers. There was a family history of similar symptoms in their cousin brother. All the four siblings were product of consanguineous marriage. Their mother was suffering from discoid lupus erythematosus. Conclusion: Timely diagnosis of Ushers could have decreased the morbidity of these children. Universal Screening for newborn hearing at birth will help in early detection of children with hearing loss and associated syndromes. Cochlear implantation is the only treatment in Ushers and earlier the implantation better is the prognosis. Hence in developing countries like India where genetic diagnosis is not possible most of the times due to financial constraints we can at least implement programs like hearing screening at birth.

Rare V180I mutation in PRNP gene of a Chinese patient with Creutzfeldt-Jakob disease

Here, we reported a Chinese case of Creutzfeldt-Jakob disease (CJD) with a rare mutation in the prion protein gene (PRNP) leading to an exchange of amino acid from valine (V) to isoleucine (I) at codon 180 (V180I). The 72 year-old Chinese women started with gradual memory loss. On admission, she did not present special abnormality during clinical examinations except bradykinesia in her lower extremities. Myoclonic jerks and increased muscle tone were noticed 3 months after the onset. No periodic activity was recorded at electroencephalography (EEG) and 14-3-3 protein was negative in the cerebrospinal fluid (CSF) sample. Brain diffusion weighted images (DWI) demonstrated high signal intensities in bilateral frontal, parietal, temporal and occipital cortices, especially on the left hemisphere, and high signal intensities were also seen in the left caudate nucleus and the putamen. The patient had no family history of similar symptoms. Her general condition was gradually deteriorative, but the patient was still alive when we performed the follow-up 12 months after onset.

Two cases of Degos disease with different prognosis.

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Li Z, Jin P, Wang B, Feng S. Letter to the EditorTwo cases of Degos disease with different prognosis. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii. 2014;31(6):425-427. doi:10.5114/pdia.2014.44020. APA Li, Z., Jin, P., Wang, B., & Feng, S. (2014). Letter to the EditorTwo cases of Degos disease with different prognosis. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii, 31(6), 425-427. https://doi.org/10.5114/pdia.2014.44020 Chicago Li, Zhiliang, Peiying Jin, Baoxi Wang, and Suying Feng. 2014. "Letter to the EditorTwo cases of Degos disease with different prognosis". Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii 31 (6): 425-427. doi:10.5114/pdia.2014.44020. Harvard Li, Z., Jin, P., Wang, B., and Feng, S. (2014). Letter to the EditorTwo cases of Degos disease with different prognosis. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii, 31(6), pp.425-427. https://doi.org/10.5114/pdia.2014.44020 MLA Li, Zhiliang et al. "Letter to the EditorTwo cases of Degos disease with different prognosis." Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii, vol. 31, no. 6, 2014, pp. 425-427. doi:10.5114/pdia.2014.44020. Vancouver Li Z, Jin P, Wang B, Feng S. Letter to the EditorTwo cases of Degos disease with different prognosis. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii. 2014;31(6):425-427. doi:10.5114/pdia.2014.44020.

Delayed diagnosis of oculopharyngeal muscular dystrophy in Denmark: from initial ptosis to genetic testing

Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset dominantly inherited myopathy. Its genetic basis has been identified as a trinucleotide repeat expansion ranging from (GCG)8 to (GCG)13 in the N-terminus polyalanine domain of the PABPN1 gene on chromosome 14q11. Affected members present with progressive ptosis and ophthalmoplegia, swallowing difficulties and proximal limb weakness in a context of a family history with dominant transmission (Brais et al. 1999). This condition is commonly described in French and Canadian families, but some sporadic cases have been reported in various countries (Müller et al. 2006; Rodriguez et al. 2005, Hill et al. 2001). There does not appear to be differences in the clinical course of OPMD based on regions; however, delay in the diagnosis may occur because of the slow progression of symptoms, low prevalence and lack of awareness among ophthalmologists. Our cross-sectional study reports the clinical presentations and treatment of 14 patients from 8 unrelated Danish families with genetically confirmed OPMD. The study was conducted in accordance with the International Conference of Harmonization Good Clinical Practice guidelines and the declaration of Helsinki. The study protocol was approved by the ethics committee for the Capital Region. Written informed consent was obtained for all subjects. Patients were followed at the reference centre for neuromuscular diseases at Rigshospitalet in Copenhagen. Demographic data about sequence of symptoms, diagnosis and treatment were collected. A complete oculo-palpebral examination was performed. DNA was isolated from an EDTA blood sample by standard methods. The GCG repeats were determined by PCR. Onset of symptoms occurred at a mean age of 51 years (range 37–60). Only six patients could report a family history of ptosis and/or other neurological symptoms. A pathogenic trinucleotide expansion was identified and sequenced in all eight families. In 10 patients (77%), ptosis was the initial symptom, occurring at a mean age of 52 years (range 41–64). In three patients, limb weakness was the initial symptom, followed by ptosis. The frequency of ptosis-associated dysphagia, dysarthria and ophthalmoplegia increased with age and disease duration. Table 1 summarizes the clinical findings at inclusion. The mean delay between the presenting signs and genetic confirmation was 8 years (range 5–15). Thirteen patients were operated for ptosis, with an average of 3.5 procedures per patient. Among those, 9 (69%) were operated several times, before referral for genetic testing. As a first procedure, 11 patients underwent aponeurosis surgery and 2 had brow suspension. Six patients (55%), who underwent aponeurosis surgery with immediate insufficient results, had the procedure repeated at least once (range 1–3) before being diagnosed with OPMD. Frontal brow suspension always resulted in good functional and cosmetic results. Sporadic and familial cases of OPMD have been reported in many countries (Hill et al. 2001; Müller et al. 2006; Mihaylova et al. 2008). However, the disease has been poorly investigated in Northern Europe and has never been described in Denmark. The clinical evolution of OPMD is slow, its treatment is symptomatic, and life span is usually normal. In our series, an appropriate OPMD diagnosis at presentation was often missed, and patients were offered an aponeurotic surgery without further investigations. Repeated ptosis interventions were therefore not uncommon. Subsequent success was obtained by frontal brow suspension, which is the appropriate surgery for myopathic ptosis, in which levator palpebrae muscle function is poor (Wong et al. 2002). In conclusion, ptosis is the most common presenting sign of OPMD. An appropriate work-up of bilateral and progressive ptosis in middle-aged adults with dysphagia and/or limb weakness should include genetic screening for OPMD, especially if there is a first-degree family history of similar symptoms.