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Sjögren-Larsson syndrome(SLS)

MedGen UID:
11443
Concept ID:
C0037231
Disease or Syndrome
Synonyms: FADH deficiency; FAO deficiency; FATTY ALCOHOL:NAD+ OXIDOREDUCTASE DEFICIENCY; Fatty aldehyde dehydrogenase deficiency; Ichthyosis, spastic neurologic disorder, and oligophrenia; Sjogren-Larsson Syndrome; SLS
SNOMED CT: Sjogren-Larsson syndrome (111303009); Sjögren-Larsson syndrome (111303009); Fatty alcohol-nicotinamide adenine dinucleotide oxidoreductase deficiency (111303009); FAO - Fatty alcohol-nicotinamide adenine dinucleotide oxidase-reductase deficiency (111303009)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): ALDH3A2 (17p11.2)
 
Monarch Initiative: MONDO:0010031
OMIM®: 270200
Orphanet: ORPHA816

Definition

Sjogren-Larsson syndrome (SLS) is an autosomal recessive, early childhood-onset disorder characterized by ichthyosis, impaired intellectual development, spastic paraparesis, macular dystrophy, and leukoencephalopathy. It is caused by deficiency of fatty aldehyde dehydrogenase (summary by Lossos et al., 2006). [from OMIM]

Additional description

From MedlinePlus Genetics
Sjögren-Larsson syndrome is a condition characterized by dry, scaly skin (ichthyosis); neurological problems; and eye problems. These symptoms are apparent by early childhood and usually do not worsen with age.

Affected infants tend to be born prematurely. At birth the skin is red (erythema), but later in infancy the skin becomes dry, rough, and scaly with a brownish or yellowish tone. Mild to severe itchiness (pruritus) is also common. These skin abnormalities are generally dispersed over the whole body, most severely affecting the nape of the neck, the torso, and the extremities. The skin of the face is usually not affected.

People with this condition may also have neurological signs and symptoms. Most affected individuals have leukoencephalopathy, which is a change in a type of brain tissue called white matter. White matter consists of nerve fibers covered by a substance (myelin) that insulates and protects the nerves. The leukoencephalopathy is thought to contribute to many of the neurological signs and symptoms in people with Sjögren-Larsson syndrome. Most affected individuals have intellectual disability that varies from mild to profound and is usually apparent by early childhood. People with Sjögren-Larsson syndrome have speech difficulties (dysarthria) and delayed speech. Usually they are able to produce only short sentences with poorly formed words. Rarely, people with this condition have normal intelligence. In addition, approximately 40 percent of people with Sjögren-Larsson syndrome have seizures.

Children with this condition often experience delayed development of motor skills (such as crawling and walking) due to abnormal muscle stiffness (spasticity) that is typically in their legs and, less commonly, also in their arms. About one-half of people with Sjögren-Larsson syndrome require wheelchair assistance and many others need some form of support to walk.

Affected individuals have tiny crystals in the light-sensitive tissue at the back of the eye (retina) that can be seen during an eye exam. Based on their appearance, these retinal crystals are often called glistening white dots. These white dots are usually apparent by early childhood, and it is unclear if they affect normal vision. People with Sjögren-Larsson syndrome may also have nearsightedness (myopia) or an increased sensitivity to light (photophobia).  https://medlineplus.gov/genetics/condition/sjogren-larsson-syndrome

Clinical features

From HPO
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Spastic paraparesis
MedGen UID:
52432
Concept ID:
C0037771
Sign or Symptom
Mild or moderate loss of motor function accompanied by spasticity in the lower extremities. This condition is a manifestation of CENTRAL NERVOUS SYSTEM DISEASES that cause injury to the motor cortex or descending motor pathways.
Photophobia
MedGen UID:
43220
Concept ID:
C0085636
Sign or Symptom
Excessive sensitivity to light with the sensation of discomfort or pain in the eyes due to exposure to bright light.
CNS demyelination
MedGen UID:
137898
Concept ID:
C0338474
Disease or Syndrome
A loss of myelin from nerve fibers in the central nervous system.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Thoracic kyphosis
MedGen UID:
263148
Concept ID:
C1184919
Finding
Over curvature of the thoracic region, leading to a round back or if sever to a hump.
Enamel hypoplasia
MedGen UID:
3730
Concept ID:
C0011351
Disease or Syndrome
Developmental hypoplasia of the dental enamel.
Ichthyosis
MedGen UID:
7002
Concept ID:
C0020757
Disease or Syndrome
An abnormality of the skin characterized the presence of excessive amounts of dry surface scales on the skin resulting from an abnormality of keratinization.
Astigmatism
MedGen UID:
2473
Concept ID:
C0004106
Disease or Syndrome
Astigmatism (from the Greek 'a' meaning absence and 'stigma' meaning point) is a condition in which the parallel rays of light entering the eye through the refractive media are not focused on a single point. Both corneal and noncorneal factors contribute to refractive astigmatism. Corneal astigmatism is mainly the result of an aspheric anterior surface of the cornea, which can be measured readily by means of a keratometer; in a small fraction of cases (approximately 1 in 10) the effect is neutralized by the back surface. The curvature of the back surface of the cornea is not considered in most studies, because it is more difficult to measure; moreover, in the case of severe corneal astigmatism, there is evidence that both surfaces have the same configuration. Noncorneal factors are errors in the curvature of the 2 surfaces of the crystalline lens, irregularity in the refractive index of the lens, and an eccentric lens position. Since the cornea is the dominant component of the eye's refracting system, a highly astigmatic cornea is likely to result in a similarly astigmatic ocular refraction (summary by Clementi et al., 1998).
Macular degeneration
MedGen UID:
7434
Concept ID:
C0024437
Disease or Syndrome
A nonspecific term denoting degeneration of the retinal pigment epithelium and/or retinal photoreceptor cells of the macula lutea.
Alternating exotropia
MedGen UID:
101825
Concept ID:
C0152207
Disease or Syndrome
A type of exotropia in which either eye may be used for fixation.
Color vision defect
MedGen UID:
115964
Concept ID:
C0234629
Finding
An anomaly in the ability to discriminate between or recognize colors.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
Retinal pigment epithelial atrophy
MedGen UID:
333564
Concept ID:
C1840457
Finding
Atrophy (loss or wasting) of the retinal pigment epithelium observed on fundoscopy or fundus imaging.
Opacification of the corneal epithelium
MedGen UID:
336534
Concept ID:
C1849198
Finding
Lack of transparency of the corneal epithelium.
Retinal thinning
MedGen UID:
762617
Concept ID:
C3549703
Finding
Reduced anteroposterior thickness of the retina. This phenotype can be appreciated by retinal optical coherence tomography (OCT).
Macular crystals
MedGen UID:
892788
Concept ID:
C4072988
Finding
Crystalline deposits in the macula.
Macular dots
MedGen UID:
1671017
Concept ID:
C4732810
Finding
Yellow, white or greyish lesions in the macula that are well-defined/distinct, individual and mostly uniform in size.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSjögren-Larsson syndrome
Follow this link to review classifications for Sjögren-Larsson syndrome in Orphanet.

Professional guidelines

PubMed

Weustenfeld M, Eidelpes R, Schmuth M, Rizzo WB, Zschocke J, Keller MA
Hum Mutat 2019 Feb;40(2):177-186. Epub 2018 Nov 26 doi: 10.1002/humu.23679. PMID: 30372562Free PMC Article
DiGiovanna JJ, Robinson-Bostom L
Am J Clin Dermatol 2003;4(2):81-95. doi: 10.2165/00128071-200304020-00002. PMID: 12553849
Nadim F, Walid H, Adib J
Int Ophthalmol 2001;24(3):113-21. doi: 10.1023/a:1021189215498. PMID: 12498506

Recent clinical studies

Etiology

Franzen MH, LeRiger MM, Pellegrino KP, Kugler JA, Rizzo WB
Paediatr Anaesth 2020 Dec;30(12):1390-1395. Epub 2020 Oct 26 doi: 10.1111/pan.14034. PMID: 33037729Free PMC Article
Craiglow BG
Semin Perinatol 2013 Feb;37(1):26-31. doi: 10.1053/j.semperi.2012.11.001. PMID: 23419760Free PMC Article
Lamari F, Mochel F, Sedel F, Saudubray JM
J Inherit Metab Dis 2013 May;36(3):411-25. Epub 2012 Jul 20 doi: 10.1007/s10545-012-9509-7. PMID: 22814679
DiGiovanna JJ, Robinson-Bostom L
Am J Clin Dermatol 2003;4(2):81-95. doi: 10.2165/00128071-200304020-00002. PMID: 12553849
Sood M, Trehan A, Dinakaran J, Marwaha RK
Indian J Pediatr 2002 Feb;69(2):193-4. doi: 10.1007/BF02859387. PMID: 11929038

Diagnosis

Pawar N, Meenakshi R, Maheshwari D, Fathima A, Chakrabarty S, Paranjape M
Indian J Ophthalmol 2022 Jul;70(7):2727-2728. doi: 10.4103/ijo.IJO_2994_21. PMID: 35791223Free PMC Article
Cho KH, Shim SH, Kim M
Clin Genet 2018 Apr;93(4):721-730. Epub 2017 Sep 17 doi: 10.1111/cge.13058. PMID: 28543186
Yoneda K
J Dermatol 2016 Mar;43(3):252-63. doi: 10.1111/1346-8138.13284. PMID: 26945533
Dutra LA, Braga-Neto P, Pedroso JL, Povoas Barsottini OG
Adv Exp Med Biol 2012;724:344-50. doi: 10.1007/978-1-4614-0653-2_26. PMID: 22411255
Gordon N
Dev Med Child Neurol 2007 Feb;49(2):152-4. doi: 10.1111/j.1469-8749.2007.00152.x. PMID: 17254005

Therapy

Xu YC, Hou JQ, Zhu WJ, Li P
J Cosmet Dermatol 2020 Apr;19(4):789-798. Epub 2019 Nov 7 doi: 10.1111/jocd.13209. PMID: 31697031
Vural S, Vural A, Akçimen F, Bağci IS, Tunca C, Gündoğdu Eken A, Ruzicka T, Başak AN
Int J Dermatol 2018 Jul;57(7):843-848. Epub 2018 Apr 27 doi: 10.1111/ijd.14013. PMID: 29704247
Hidalgo ET, Orillac C, Hersh A, Harter DH, Rizzo WB, Weiner HL
J Child Neurol 2017 Jan;32(1):100-103. Epub 2016 Oct 6 doi: 10.1177/0883073816671440. PMID: 28257279Free PMC Article
Fuijkschot J, Theelen T, Seyger MM, van der Graaf M, de Groot IJ, Wevers RA, Wanders RJ, Waterham HR, Willemsen MA
J Inherit Metab Dis 2012 Nov;35(6):955-62. Epub 2012 Jul 26 doi: 10.1007/s10545-012-9518-6. PMID: 22833178
DiGiovanna JJ, Robinson-Bostom L
Am J Clin Dermatol 2003;4(2):81-95. doi: 10.2165/00128071-200304020-00002. PMID: 12553849

Prognosis

Warrack S, Love T, Rizzo WB
J Child Neurol 2021 Oct;36(11):1011-1016. Epub 2021 Jul 28 doi: 10.1177/08830738211029390. PMID: 34315315Free PMC Article
Cho KH, Shim SH, Kim M
Clin Genet 2018 Apr;93(4):721-730. Epub 2017 Sep 17 doi: 10.1111/cge.13058. PMID: 28543186
Priyadharshini Christy J, George Priya Doss C
Front Biosci (Landmark Ed) 2015 Jan 1;20(2):335-76. doi: 10.2741/4313. PMID: 25553455
DiGiovanna JJ, Robinson-Bostom L
Am J Clin Dermatol 2003;4(2):81-95. doi: 10.2165/00128071-200304020-00002. PMID: 12553849
Sood M, Trehan A, Dinakaran J, Marwaha RK
Indian J Pediatr 2002 Feb;69(2):193-4. doi: 10.1007/BF02859387. PMID: 11929038

Clinical prediction guides

Arai A, Takeichi T, Wakamoto H, Sassa T, Ito Y, Murase Y, Ogi T, Akiyama M, Kihara A
J Dermatol Sci 2022 Sep;107(3):114-122. Epub 2022 Aug 9 doi: 10.1016/j.jdermsci.2022.08.003. PMID: 35973883
Franzen MH, LeRiger MM, Pellegrino KP, Kugler JA, Rizzo WB
Paediatr Anaesth 2020 Dec;30(12):1390-1395. Epub 2020 Oct 26 doi: 10.1111/pan.14034. PMID: 33037729Free PMC Article
Weustenfeld M, Eidelpes R, Schmuth M, Rizzo WB, Zschocke J, Keller MA
Hum Mutat 2019 Feb;40(2):177-186. Epub 2018 Nov 26 doi: 10.1002/humu.23679. PMID: 30372562Free PMC Article
Malheiro AR, da Silva TF, Brites P
J Inherit Metab Dis 2015 Jan;38(1):111-21. Epub 2014 Nov 29 doi: 10.1007/s10545-014-9795-3. PMID: 25432520
Willemsen MA, IJlst L, Steijlen PM, Rotteveel JJ, de Jong JG, van Domburg PH, Mayatepek E, Gabreëls FJ, Wanders RJ
Brain 2001 Jul;124(Pt 7):1426-37. doi: 10.1093/brain/124.7.1426. PMID: 11408337

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