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In this article, we describe three patients; two diagnosed with Heimler syndrome and a third one with a mild\u2010intermediate phenotype. We arrived at these diagnoses by conducting complete ophthalmic (National Eye Institute), auditory (National Institute of Deafness and Other Communication Disorders), and dental (National Institute of Dental and Craniofacial Research) evaluations, as well as laboratory and genetic testing. Retinal degeneration with macular cystic changes, amelogenesis imperfecta, and sensorineural hearing loss were features shared by the three patients. Patients A and C had pathogenic variants in<jats:italic>PEX1<\/jats:italic>and Patient B, in<jats:italic>PEX6<\/jats:italic>. Besides analyzing these cases, we review the literature regarding mild peroxisomal disorders, their pathophysiology, genetics, differential diagnosis, diagnostic methods, and management. We suggest that peroxisomal disorders are considered in every child with sensorineural hearing loss and retinal degeneration. These patients should have a dental evaluation to rule out amelogenesis imperfecta as well as audiologic examination and laboratory testing including peroxisomal biomarkers and genetic testing. Appropriate diagnosis can lead to better genetic counseling and management of the associated comorbidities.<\/jats:p>","DOI":"10.1002\/ajmg.c.31823","type":"journal-article","created":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T17:56:58Z","timestamp":1598896618000},"page":"618-630","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The peroxisomal disorder spectrum and Heimler syndrome: Deep phenotyping and review of the literature"],"prefix":"10.1002","volume":"184","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4960-4510","authenticated-orcid":false,"given":"Malena Daich","family":"Varela","sequence":"first","affiliation":[{"name":"Ophthalmic Genetics and Visual Function Branch National Eye Institute, National Institutes of Health (NIH) Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyam","family":"Jani","sequence":"additional","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, NIH Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wadih M.","family":"Zein","sequence":"additional","affiliation":[{"name":"Ophthalmic Genetics and Visual Function Branch National Eye Institute, National Institutes of Health (NIH) Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Precilla","family":"D'Souza","sequence":"additional","affiliation":[{"name":"Office of the Clinical Director National Human Genome Research Institute, NIH Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynne","family":"Wolfe","sequence":"additional","affiliation":[{"name":"Undiagnosed Diseases Program Common Fund, NIH Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Chisholm","sequence":"additional","affiliation":[{"name":"Audiology Unit, Otolaryngology Branch National Institute on Deafness and Other Communication Disorders, NIH Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Zalewski","sequence":"additional","affiliation":[{"name":"Audiology Unit, Otolaryngology Branch National Institute on Deafness and Other Communication Disorders, NIH Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Adams","sequence":"additional","affiliation":[{"name":"Office of the Clinical Director National Human Genome Research Institute, NIH Bethesda Maryland USA"},{"name":"Undiagnosed Diseases Program Common Fund, NIH Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blake M.","family":"Warner","sequence":"additional","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, NIH Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laryssa A.","family":"Huryn","sequence":"additional","affiliation":[{"name":"Ophthalmic Genetics and Visual Function Branch National Eye Institute, National Institutes of Health (NIH) Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"Hufnagel","sequence":"additional","affiliation":[{"name":"Ophthalmic Genetics and Visual Function Branch National Eye Institute, National Institutes of Health (NIH) Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,31]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1754-4505.2012.00248.x"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jog.12379"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpm.2004.05.005"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-1788-0_4"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2015.12.009"},{"issue":"6","key":"e_1_2_5_7_1","first-page":"344","article-title":"Cerebro\u2010hepato\u2010renal (Zellweger) syndrome and neonatal adrenoleukodystrophy: Similarities in phenotype and accumulation of very long chain fatty acids","volume":"151","author":"Brown F. 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