peroxisome biogenesis disorder 4C

Heimler Syndrome 2

Clinical Characteristics
Ocular Features: 

Several cases have been reported with macular dystrophy and 'salt-and-pepper' mottling of the RPE extending to the midperiphery with foveal sparing.  Autofluorescence with hyper- and hypo-autofluorescent dots has been observed in the mottled areas of the RPE.  Spectral domain OCT has shown loss of the inner/outer segment boundary with RPE thinning and multiple retinal cysts but the ERG does not show rod-cone dysfunction. Visual acuity and the ocular fundus were normal in one patient until the age of 29 years when her vision dropped to 20/200 in one eye and 20/40 in the other.

Systemic Features: 

Primary dentition may be normal but secondary teeth have enamel hypoplasia (amelogenesis imperfecta).  The nails have Beau lines (transverse ridges) and leukonychia (white spots).  Severe sensorineural hearing loss develops sometime in the first year or two of life and it may be unilateral. At least one patient was documented to have had normal audiological test results until the age of 3 years.

Psychomotor development is normal at least until sensory deprivation occurs.


This is a rare syndrome of ectodermally derived tissue which results from compound heterozygous mutations in the PEX6 gene (6p21.1).  A pair of monozygotic twin girls with this syndrome has been reported.  Parents are phenotypically normal.  No instance of parent-to-child transmission has been noted and it seems likely that this is an autosomal recessive disorder.

Another form of Heimler syndrome (234580) but with compound heterozygous mutations in the PEX1 gene (7q21.2) has been reported.

Autosomal recessive
Treatment Options: 

One patient has been treated with carbonic anhydrase inhibitors with apparent stabilization of vision.  Low vision aids and assistive hearing devices are likely of benefit for at least some patients.

Article Title: 

Spectrum of PEX1 and PEX6 variants in Heimler syndrome

Smith CE, Poulter JA, Levin AV, Capasso JE, Price S, Ben-Yosef T, Sharony R, Newman WG, Shore RC, Brookes SJ, Mighell AJ, Inglehearn CF. Spectrum of PEX1 and PEX6 variants in Heimler syndrome. Eur J Hum Genet. 2016 Nov;24(11):1565-1571.

PubMed ID: 

Macular dystrophy in Heimler syndrome

Lima LH, Barbazetto IA, Chen R, Yannuzzi LA, Tsang SH, Spaide RF. Macular dystrophy in Heimler syndrome. Ophthalmic Genet. 2011 Jun;32(2):97-100.

PubMed ID: 
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