Letter to the Editor
Camptocormia as the main manifestation of a mutation in the POLG gene
Camptocormia como principal manifestación de mutación en el gen POLG
A. Sancho Saldaña
, A. Lázaro Romero, J.L. Capablo Liesa, R. Alarcia Alejos
Corresponding author
Servicio de Neurología, Hospital Universitario Miguel Servet, Zaragoza, Spain
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Sancho Saldaña, A. Lázaro Romero, J.L. Capablo Liesa, R. Alarcia Alejos" "autores" => array:4 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Sancho Saldaña" "email" => array:1 [ 0 => "agustinsanchosaldana@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Lázaro Romero" ] 2 => array:2 [ "nombre" => "J.L." "apellidos" => "Capablo Liesa" ] 3 => array:2 [ "nombre" => "R." "apellidos" => "Alarcia Alejos" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Neurología, Hospital Universitario Miguel Servet, Zaragoza, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Camptocormia como principal manifestación de mutación en el gen <span class="elsevierStyleItalic">POLG</span>" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 888 "Ancho" => 1300 "Tamanyo" => 93284 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The patient before (A) and one hour after (B) a 350 mg dose of levodopa, showing a clear improvement in the anteroflexion of the trunk.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The term camptocormia refers to marked flexion of the thoracolumbar spine, which resolves with supine positions, in the absence of fixed deformity.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> This symptom may have multiple aetiologies, including parkinsonian syndromes, paraspinal myopathies, dystonia, motor neuron diseases, and functional disorders.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3</span></a> In exceptional cases, it can also be associated with <span class="elsevierStyleItalic">POLG</span> mutations.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 52-year-old man with history of mild psychomotor retardation since childhood; his father had late-onset Parkinson’s disease and his mother had essential tremor. His 2 older siblings were asymptomatic. The patient was referred to our department due to progressive anteroflexion of the trunk of 4 years’ progression, which hindered walking and was associated with poor coordination and slow movement, mainly affecting the right side; these symptoms were highly disabling. He displayed no signs of dysautonomia, with the exception of constipation.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Neurological examination revealed hypomimia, moderate bilateral bradykinesia, mainly affecting the right side, and low-amplitude right-sided resting tremor. Eye movement was not restricted. When standing, the patient displayed forced anteroflexion of the trunk, with the waist at an angle of approximately 70° (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). In the decubitus position, he was able to correct his posture, lying flat on the bed.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">A complete blood analysis including copper metabolism, muscle enzymes, and lactate detected no abnormalities; serology results for syphilis and HIV were negative. A brain MRI study detected no relevant alterations. A DaTSCAN study revealed dopamine transporter inactivity in both putamina and reduced uptake in the left caudate nucleus.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In the light of these findings, treatment was started with levodopa at increasing doses of up to 250 mg/6 hours, with a suboptimal response. After a 350 mg loading dose, he presented an improvement of over 30% on the UPDRS part III motor examination, with his posture improving and stabilising. The extreme anteroflexion of the trunk (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) resolved, and he was able to carefully walk over 20 metres unassisted.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Given the history of psychomotor delay and the atypical parkinsonian symptoms, we requested an exome sequencing study, which identified a heterozygous missense mutation in exon 20 of the <span class="elsevierStyleItalic">POLG</span> gene (C.3218c > T; p [Pro1073Leu]), located on chromosome 15. The mutation is listed on the ClinVar and HGMD databases as a pathogenic variant. Functional studies have shown that this variant also affects mitochondrial DNA replication.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Despite the lack of clear symptoms, we performed further diagnostic testing. An electromyoneurography study yielded normal results, and a multidisciplinary evaluation identified mild bilateral cataracts and predominantly sensorineural mixed hearing loss.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">POLG</span> gene encodes the catalytic subunit of DNA polymerase gamma, which is responsible for the replication of the mitochondrial genome.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Mutations of the gene are associated with a broad spectrum of neurological syndromes, with age of onset ranging from infancy to adulthood; manifestations include epilepsy, psychiatric disorders, polyneuropathy, myopathy, ataxia, and progressive external ophthalmoplegia, and may be associated with such non-neurological conditions as cataracts, sensorineural hearing loss, and premature ovarian failure.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">More rarely, <span class="elsevierStyleItalic">POLG</span> mutations may be associated with parkinsonism,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> often preceded for several years by classical phenotypes: usually progressive external ophthalmoplegia,<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> but also sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO).<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> In these patients, parkinsonism tends to be asymmetrical, with onset occurring around the age of 40 years and good response to levodopa.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,10</span></a> Our patient developed an atypical parkinsonian syndrome, with no evidence of other neurological characteristics associated with <span class="elsevierStyleItalic">POLG</span> mutations; prominent camptocormia was the most striking symptom. Additional tests performed after diagnosis identified bilateral cataracts and mild sensorineural hearing loss; these findings are associated with the mutation. This form of presentation, in which the parkinsonian syndrome is not preceded by ophthalmoparesis, has only been described in 2 patients also presenting peripheral neuropathy<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> and in a patient with another pathogenic mutation in the <span class="elsevierStyleItalic">GBA</span> gene.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> We believe that the cause of camptocormia in our patient was parkinsonism itself, as he presented severe anteroflexion of the trunk and absence of abnormal postures in the head and neck (as would be the case for dystonic camptocormia), and posture improved (albeit suboptimally) with levodopa. Furthermore, the electromyography study showed no myopathic changes.</p><p id="par0050" class="elsevierStylePara elsevierViewall">In conclusion, our patient presented a unique phenotype of <span class="elsevierStyleItalic">POLG</span> mutation, presenting with camptocormia secondary to atypical parkinsonism not preceded by SANDO or progressive external ophthalmoplegia, which has rarely been described in the literature.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleItalic">POLG</span> mutations should be considered in the differential diagnosis of atypical parkinsonism, even in patients without ophthalmoparesis or polyneuropathy.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-03-19" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Sancho Saldaña A, et al. Camptocormia como principal manifestación de mutación en el gen <span class="elsevierStyleItalic">POLG</span>. Neurología. 2021;36:390–392.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 888 "Ancho" => 1300 "Tamanyo" => 93284 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The patient before (A) and one hour after (B) a 350 mg dose of levodopa, showing a clear improvement in the anteroflexion of the trunk.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:13 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Camptocormia: etiology, diagnosis, and treatment response" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "F. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 3 | 9 |
| 2024 October | 40 | 13 | 53 |
| 2024 September | 36 | 17 | 53 |
| 2024 August | 55 | 16 | 71 |
| 2024 July | 36 | 9 | 45 |
| 2024 June | 36 | 3 | 39 |
| 2024 May | 33 | 3 | 36 |
| 2024 April | 25 | 6 | 31 |
| 2024 March | 39 | 10 | 49 |
| 2024 February | 63 | 6 | 69 |
| 2024 January | 58 | 3 | 61 |
| 2023 December | 45 | 9 | 54 |
| 2023 November | 62 | 11 | 73 |
| 2023 October | 67 | 10 | 77 |
| 2023 September | 35 | 7 | 42 |
| 2023 August | 20 | 5 | 25 |
| 2023 July | 38 | 5 | 43 |
| 2023 June | 38 | 6 | 44 |
| 2023 May | 58 | 12 | 70 |
| 2023 April | 40 | 3 | 43 |
| 2023 March | 28 | 12 | 40 |
| 2023 February | 21 | 0 | 21 |
| 2023 January | 36 | 3 | 39 |
| 2022 December | 41 | 13 | 54 |
| 2022 November | 40 | 18 | 58 |
| 2022 October | 36 | 16 | 52 |
| 2022 September | 33 | 5 | 38 |
| 2022 August | 46 | 19 | 65 |
| 2022 July | 24 | 8 | 32 |
| 2022 June | 40 | 7 | 47 |
| 2022 May | 38 | 10 | 48 |
| 2022 April | 40 | 10 | 50 |
| 2022 March | 43 | 14 | 57 |
| 2022 February | 32 | 8 | 40 |
| 2022 January | 45 | 6 | 51 |
| 2021 December | 51 | 14 | 65 |
| 2021 November | 45 | 13 | 58 |
| 2021 October | 85 | 14 | 99 |
| 2021 September | 33 | 18 | 51 |
| 2021 August | 51 | 9 | 60 |
| 2021 July | 30 | 17 | 47 |
| 2021 June | 19 | 6 | 25 |
| 2021 May | 14 | 15 | 29 |
| 2021 April | 16 | 22 | 38 |
| 2021 March | 13 | 1 | 14 |
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