Abstract
Heimler syndrome is a rare syndrome associating sensorineural hearing loss with retinal dystrophy and amelogenesis imperfecta due to PEX1 or PEX6 biallelic pathogenic variations. This syndrome is one of the less severe forms of peroxisome biogenesis disorders. In this chapter, we will review clinical, biological, and genetic knowledges about the Heimler syndrome.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Heimler A, Fox JE, Hershey JE, Crespi P (1991) Sensorineural hearing loss, enamel hypoplasia, and nail abnormalities in sibs. Am J Med Genet 39:192–195
Acharya BS, Ritwik P, Velasquez GM, Fenton SJ (2012) Medical-dental findings and management of a child with infantile Refsum disease: a case report: infantile refsum disease-dental management. Spec Care Dentist 32:112–117
Zaki MS, Heller R, Thoenes M, Nürnberg G, Stern-Schneider G, Nürnberg P, Karnati S, Swan D, Fateen E, Nagel-Wolfrum K et al (2016) PEX6 is expressed in photoreceptor cilia and mutated in deafblindness with enamel dysplasia and microcephaly: human mutation. Hum Mutat 37:170–174
Dure-Molla M, Fournier BP, Manzanares MC, Acevedo AC, Hennekam RC, Friedlander L, Boy-Lefèvre M, Kerner S, Toupenay S, Garrec P et al (2019) Elements of morphology: standard terminology for the teeth and classifying genetic dental disorders. Am J Med Genet A 179:1913–1981
Ong KR, Visram S, McKaig S, Brueton LA (2006) Sensorineural deafness, enamel abnormalities and nail abnormalities: a case report of Heimler syndrome in identical twin girls. Eur J Med Genet 49:187–193
Pollak C, Floy M, Say B (2003) Sensorineural hearing loss and enamel hypoplasia with subtle nail findings: another family with Heimlerʼs syndrome. Clin Dysmorphol 12:55–58
Ratbi I, Jaouad IC, Elorch H, Al-Sheqaih N, Elalloussi M, Lyahyai J, Berraho A, Newman WG, Sefiani A (2016) Severe early onset retinitis pigmentosa in a Moroccan patient with Heimler syndrome due to novel homozygous mutation of PEX1 gene. Eur J Med Genet 59:507–511
Smith CEL, Poulter JA, Levin AV, Capasso JE, Price S, Ben-Yosef T, Sharony R, Newman WG, Shore RC, Brookes SJ et al (2016) Spectrum of PEX1 and PEX6 variants in Heimler syndrome. Eur J Hum Genet 24:1565–1571
Ratbi I, Falkenberg KD, Sommen M, Al-Sheqaih N, Guaoua S, Vandeweyer G, Urquhart JE, Chandler KE, Williams SG, Roberts NA et al (2015) Heimler syndrome is caused by hypomorphic mutations in the peroxisome-biogenesis genes PEX1 and PEX6. Am J Hum Genet 97:535–545
Wangtiraumnuay N, Alnabi WA, Tsukikawa M, Thau A, Capasso J, Sharony R, Inglehearn CF, Levin AV (2018) Ophthalmic manifestations of Heimler syndrome due to PEX6 mutations. Ophthalmic Genet 39:384–390
Lima LH, Barbazetto IA, Chen R, Yannuzzi LA, Tsang SH, Spaide RF (2011) Macular dystrophy in Heimler syndrome. Ophthalmic Genet 32:97–100
Ebberink MS, Mooijer PAW, Gootjes J, Koster J, Wanders RJA, Waterham HR (2011) Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder. Hum Mutat 32:59–69
Maxwell MA, Allen T, Solly PB, Svingen T, Paton BC, Crane DI (2002) NovelPEX1 mutations and genotype-phenotype correlations in Australasian peroxisome biogenesis disorder patients. Hum Mutat 20:342–351
Ebberink MS, Kofster J, Wanders RJA, Waterham HR (2010) Spectrum of PEX6 mutations in Zellweger syndrome spectrum patients. Hum Mutat 31:E1058–E1070
Steinberg S, Chen L, Wei L, Moser A, Moser H, Cutting G, Braverman N (2004) The PEX gene screen: molecular diagnosis of peroxisome biogenesis disorders in the Zellweger syndrome spectrum. Mol Genet Metab 83:252–263
Yik WY, Steinberg SJ, Moser AB, Moser HW, Hacia JG (2009) Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders. Hum Mutat 30:E467–E480
Gootjes J, Schmohl F, Mooijer PAW, Dekker C, Mandel H, Topcu M, Huemer M, von Schütz M, Marquardt T, Smeitink JA et al (2004) Identification of the molecular defect in patients with peroxisomal mosaicism using a novel method involving culturing of cells at 40 °C: implications for other inborn errors of metabolism: molecular analysis of peroxisome mosaicism patients. Hum Mutat 24:130–139
Imamura A, Shimozawa N, Suzuki Y, Zhang Z, Tsukamoto T, Fujiki Y, Orii T, Osumi T, Kondo N (2000) Restoration of biochemical function of the peroxisome in the temperature-sensitive mild forms of peroxisome biogenesis disorder in humans. Brain Dev 22:8–12
Delmaghani S, Defourny J, Aghaie A, Beurg M, Dulon D, Thelen N, Perfettini I, Zelles T, Aller M, Meyer A et al (2015) Hypervulnerability to sound exposure through impaired adaptive proliferation of peroxisomes. Cell 163:894–906
Marcé-Grau A, Martí-Sánchez L, Baide-Mairena H, Ortigoza-Escobar JD, Pérez-Dueñas B (2019) Genetic defects of thiamine transport and metabolism: a review of clinical phenotypes, genetics and functional studies. J Inherit Metab Dis 12125
Argyriou C, Polosa A, Cecyre B, Hsieh M, Di Pietro E, Cui W, Bouchard J-F, Lachapelle P, Braverman N (2019) A longitudinal study of retinopathy in the PEX1-Gly844Asp mouse model for mild Zellweger Spectrum Disorder. Exp Eye Res 186:107713
Stelzig I, Karnati S, Valerius KP, Baumgart-Vogt E (2013) Peroxisomes in dental tissues of the mouse. Histochem Cell Biol 140:443–462
Neuhaus C, Eisenberger T, Decker C, Nagl S, Blank C, Pfister M, Kennerknecht I, Müller-Hofstede C, Charbel Issa P, Heller R et al (2017) Next-generation sequencing reveals the mutational landscape of clinically diagnosed Usher syndrome: copy number variations, phenocopies, a predominant target for translational read-through, and PEX26 mutated in Heimler syndrome. Mol Genet Genomic Med 5:531–552
Matsumoto N, Tamura S, Furuki S, Miyata N, Moser A, Shimozawa N, Moser HW, Suzuki Y, Kondo N, Fujiki Y (2003) Mutations in novel peroxin gene PEX26 that cause peroxisome-biogenesis disorders of complementation group 8 provide a genotype-phenotype correlation. Am J Hum Genet 73:233–246
Tanaka AJ, Okumoto K, Tamura S, Abe Y, Hirsch Y, Deng L, Ekstein J, Chung WK, Fujiki Y (2019) A newly identified mutation in the PEX26 gene is associated with a milder form of Zellweger spectrum disorder. Mol Case Stud 5:a003483
Raas-Rothschild A, Wanders RJA, Mooijer PAW, Gootjes J, Waterham HR, Gutman A, Suzuki Y, Shimozawa N, Kondo N, Eshel G et al (2002) A PEX6-defective peroxisomal biogenesis disorder with severe phenotype in an infant, versus mild phenotype resembling usher syndrome in the affected parents. Am J Hum Genet 70:1062–1068
Daneshmandpour Y, Darvish H, Pashazadeh F, Emamalizadeh B (2019) Features, genetics and their correlation in Jalili syndrome: a systematic review. J Med Genet 56:358–369
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Mechaussier, S. et al. (2020). Heimler Syndrome. In: Lizard, G. (eds) Peroxisome Biology: Experimental Models, Peroxisomal Disorders and Neurological Diseases. Advances in Experimental Medicine and Biology, vol 1299. Springer, Cham. https://doi.org/10.1007/978-3-030-60204-8_7
Download citation
DOI: https://doi.org/10.1007/978-3-030-60204-8_7
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-60203-1
Online ISBN: 978-3-030-60204-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)