Sjögren‐Larsson syndrome: The mild end of the phenotypic spectrum

Staps, Pippa; Gaalen, Judith van; Domburg, Peter van; Steijlen, P.M.; Ferdinandusse, Sacha; Heijer, Tom den; Seyger, M.M.B.; Theelen, Thomas; Willemsen, M.A.A.P.

doi:10.1002/jmd2.12099

Cited by 5 publications

(7 citation statements)

References 30 publications

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“…Together with the mildly affected patients with Sjögren-Larsson syndrome, 7 the severe neurodegenerative cases represent the extremes of the phenotypic spectrum in this disease. The prevalence of a neurodegenerative phenotype in Sjögren-Larsson syndrome is not known, but it must represent a small proportion of the population.…”

Section: Discussionmentioning

confidence: 99%

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A Neurodegenerative Phenotype Associated With Sjögren-Larsson Syndrome

2021

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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.

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Section: Discussionmentioning

confidence: 99%

“…Conversely, a milder neurologic phenotype has been recognized in patients. 7 The ALDH3A2 genotype does not correlate with clinical severity of Sjögren-Larsson syndrome, 5 suggesting the presence of modifying genes or environmental influences.…”

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confidence: 99%

A Neurodegenerative Phenotype Associated With Sjögren-Larsson Syndrome

2021

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“…Although to date no explanation has fully accounted for why some individuals have more mild phenotypes, possible explanations have been proposed to include revertant mosaicism 32 or compensatory, alternative metabolic pathways upstream of the defect in FALDH that allow some individuals to escape the metabolic defect. 33 No specific therapies for SLS currently exist. Treatment is limited to the management of symptoms and physical therapy to counteract spasticity and to preserve mobility.…”

Section: Therapeutic Advances In Rare Diseasementioning

confidence: 99%

End-stage crystalline maculopathy with retinal atrophy in Sjögren-Larsson syndrome: a case report and review of the literature

Lambert

Shaikh

Marx

et al. 2022

Therapeutic Advances in Rare Disease

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Sjögren-Larsson syndrome (SLS) is a rare, autosomal recessive neurocutaneous disorder. It is caused by the inheritance of sequence variants in the ALDH3A2 gene, which codes for fatty aldehyde dehydrogenase (FALDH). Universal signs of the condition are congenital ichthyosis, spastic paresis of the lower and upper limbs, and reduced intellectual ability. In addition to this clinical triad, patients with SLS experience dry eyes and decreased visual acuity caused by a progressive retinal degeneration. Examination of the retina in patients with SLS often reveals glistening yellow crystal-like deposits surrounding the fovea. This crystalline retinopathy often develops in childhood and is considered pathognomonic for the disease. The metabolic disorder typically shortens lifespan to half that of the unaffected population. However, now that patients with SLS live longer, it becomes increasingly important to understand the natural course of the disease. Our case describes a 58-year-old woman with advanced SLS whose ophthalmic examination illustrates the end-stage of the retinal degeneration. Optical coherence tomography (OCT) and fluorescein angiography confirm the disease is restricted to the neural retina with dramatic thinning of the macula. This case is unique since it is among the most advanced both in terms of chronological age and severity of retinal disease. While the accumulation of fatty aldehydes, alcohols, and other precursor molecules is the probable cause of retinal toxicity, a more complete understanding of the course of retinal degeneration may aid in the development of future treatments. The aim of our presentation of this case is to increase awareness of the disease and to foster interest in therapeutic research which may benefit patients with this rare condition. Plain Language Summary Eye issues in Sjogren-Larsson Syndrome Sjögren-Larsson syndrome (SLS) is a rare, inherited condition that affects the skin and nervous system. It is caused by variations in a gene that controls the way fats are broken down in the body. The three key signs of the disease are (1) peeling, dry skin; (2) muscle stiffness and impaired movement of the arms and legs; and (3) reduced intellectual ability. Most signs of the condition appear shortly after birth. Genetic testing and counseling services can help patients and their families to understand what to expect with SLS. Caring for people with SLS requires teamwork by specialists like neurologists and physical therapists. Because eye problems are common, the early consultation of an eye doctor is also important. An eye examination can also confirm the diagnosis of SLS. SLS often causes the eyes to appear red, feel dry, or become irritated. This can make it hard to see in bright light. Decreased vision at night is also common. This is caused by the progressive loss of the central part of the retina which is needed to see fine details. Because SLS shortens lifespan, it is rare for anyone to reach the final stages of the disease. As patients with SLS are living longer, as illustrated by the individual in our case study, it becomes important to understand how the disease progresses. Unfortunately, treatments to restore vision are not yet available. Nevertheless, some protective measures can be taken. Eye examinations in early childhood are important for preventing damage to the eyes. Wearing glasses can improve vision, as well as protect eyes from accidental injury or falls. Eye drops can provide relief from dry eyes, and sunglasses can reduce glare and sensitivity to light. In the future, gene therapy may be used to treat SLS.

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“…Contractures in the hips and lower extremities are the norm, whereas upper extremity contractures are more unusual. Intellectual disability is equally divided between mild, moderate, or profound, 2 though rare patients with normal intelligence have been reported 6 . In the majority of cases, patients reach a functional daily living ceiling of about 12 years of age 7 .…”

Section: Introductionmentioning

confidence: 99%

“…Intellectual disability is equally divided between mild, moderate, or profound, 2 though rare patients with normal intelligence have been reported. 6 In the majority of cases, patients reach a functional daily living ceiling of about 12 years of age. 7 Seizures occur in 40% of patients and are generally well managed with anti-epileptic therapy.…”

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confidence: 99%

Sjögren‐Larsson syndrome: Anesthetic considerations and practical recommendations

Franzen

LeRiger

Pellegrino

et al. 2020

Pediatric Anesthesia

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Sjögren-Larsson syndrome (SLS) is a rare inherited neurocutaneous disorder characterized by ichthyosis, spasticity, intellectual disability, seizures, and ophthalmologic changes. 1-3 The disease was first recognized more than 60 years ago by Sjögren and Larsson, who described a cohort of patients living in northern Sweden. 4 Subsequent cases were identified in countries and ethnic groups throughout the world.

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Sjögren‐Larsson syndrome: The mild end of the phenotypic spectrum

Cited by 5 publications

References 30 publications

A Neurodegenerative Phenotype Associated With Sjögren-Larsson Syndrome

A Neurodegenerative Phenotype Associated With Sjögren-Larsson Syndrome

End-stage crystalline maculopathy with retinal atrophy in Sjögren-Larsson syndrome: a case report and review of the literature

Sjögren‐Larsson syndrome: Anesthetic considerations and practical recommendations

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