A Neurodegenerative Phenotype Associated With Sjögren-Larsson Syndrome

Abstract

Sjögren-Larsson syndrome (SLS) is a rare neurologic disorder caused by pathogenic sequence variants in ALDH3A2 and characterized by ichthyosis, spasticity, intellectual disability, and a crystalline retinopathy. Neurologic symptoms develop in the first 2 years of life. Except for worsening ambulation due to spastic diplegia and contractures, the neurologic disease has been considered static and a neurodegenerative course is distinctly unusual. We describe a young child with Sjögren-Larsson syndrome who exhibited an early and severely progressive neurologic phenotype that may have been triggered by a febrile rotavirus infection. Together with 7 additional published cases of these atypical patients, we emphasize that a neurodegenerative course can be an extreme outcome for a minority of patients with Sjögren-Larsson syndrome.

Keywords

ichthyosis spasticity intellectual disability myelin leukodystrophy

Get full access to this article

View all access options for this article.

References

Rizzo

. Sjögren-Larsson syndrome: molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency. Mol Genet Metab. 2007;90:1–9.

Rizzo

. Genetics and prospective therapeutic targets for Sjögren-Larsson syndrome. Expert Opin Orphan Drugs. 2016;4:395–406.

Sjögren

Larsson

. Oligophrenia in combination with congenital ichthyosis and spastic disorders. Acta Psychiatr Neurol Scand. 1957;32:1–113.

Jagell

Gustavson

Holmgren

Sjögren-Larsson syndrome in Sweden. A clinical, genetic and epidemiological study. Clin Genet. 1981;19:233–256.

Weustenfeld

Eidelpes

Schmuth

Rizzo

Zschocke

Keller

. Genotype and phenotype variability in Sjögren-Larsson syndrome. Hum Mutat. 2019;40(2):177–186.

Willemsen

MAAP

Van Der Graaf

Van Der Knaap

, et al. MR imaging and proton MR spectroscopic studies in Sjögren-Larsson syndrome: characterization of the leukoencephalopathy. AJNR Am J Neuroradiol. 2004;25:649–657.

Staps

van Gaalen

van Domburg

, et al. Sjögren-Larsson syndrome: the mild end of the phenotypic spectrum. JIMD Rep. 2020;53:61–70.

Engelstad

Carney

S’aulis

, et al. Large contiguous gene deletions in Sjögren-Larsson syndrome. Mol Genet Metab. 2011;104:356–361.

Davis

Holden

S’Aulis

Amador

Matheus

Rizzo

. Novel mutation in Sjögren-Larsson syndrome is associated with divergent neurologic phenotypes. J Child Neurol. 2013;28:1259–1265.

10.

Kariminejad

Barzgar

Bozorgmehr

, et al. Novel mutations and a severe neurological phenotype in Sjögren-Larsson syndrome patients from Iran. Eur J Med Genet. 2018;61:139–144.

11.

Cho

Shim

Jung

Sung

Kim

. Neurodegeneration in an adolescent with Sjögren-Larsson syndrome: a decade-long follow-up case report. BMC Med Genet. 2018;19:152.

12.

Jagell

Heijbel

. Sjögren-Larsson syndrome: physical and neurological features. A survey of 35 patients. Helv Paediatr Acta. 1982;37:519–530.

13.

De Laurenzi

Rogers

Tarcsa

, et al. Sjögren-Larsson syndrome is caused by a common mutation in northern European and Swedish patients. J Invest Dermatol. 1997;109:79–83.

14.

Sillén

Jagell

Wadelius

. A missense mutation in the FALDH gene identified in Sjögren-Larsson syndrome patients originating from the northern part of Sweden. Hum Genet. 1997;100:201–203.

15.

Rizzo

. Sjögren-Larsson syndrome: fatty aldehyde dehydrogenase deficiency. In: Scriver

, ed. The Metabolic & Molecular Bases of Inherited Disease. New York, NY: McGraw-Hill; 2001:2239–2258.

16.

Staps

Rizzo

Vaz

, et al. Disturbed brain ether lipid metabolism and histology in Sjögren-Larsson syndrome. J Inherit Metab Dis. 2020;43(6):1265–1278.