scholarly journals A Neurodegenerative Phenotype Associated With Sjögren-Larsson Syndrome

2021 ◽  
pp. 088307382110293
Author(s):  
Simone Warrack ◽  
Terri Love ◽  
William B. Rizzo
Keyword(s):  
Intellectual Disability ◽  
Young Child ◽  
Spastic Diplegia ◽  
Sequence Variants ◽  
Neurologic Disease ◽  
Neurologic Disorder ◽  
Rotavirus Infection ◽  
Neurologic Symptoms ◽  
Crystalline Retinopathy ◽  
Larsson Syndrome

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.

scholarly journals Atypical Presentation of Sjögren-Larsson Syndrome

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
D. Papathemeli ◽  
A. Mataftsi ◽  
A. Patsatsi ◽  
D. Sotiriadis ◽  
M. Samouilidou ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Spastic Diplegia ◽  
Atypical Presentation ◽  
Normal Intelligence ◽  
Neurocutaneous Disorder ◽  
Larsson Syndrome

Sjögren-Larsson syndrome is a rare neurocutaneous disorder characterized by ichthyosis, spastic diplegia or tetraplegia, and intellectual disability. Herein, we describe a case of a Greek patient with ichthyosis and spasticity of the legs but with normal intelligence (IQ 95). This syndrome should be suspected when a child presents with ichthyosis and spastic diplegia or tetraplegia, even if intelligence is normal.

Muscle Tone Assessment under General Anesthesia for Sjögren-Larsson Syndrome and Spasticity

2021 ◽  
Vol 56 (2) ◽  
pp. 163-165
Author(s):  
George Georgoulis ◽  
Argyrios Dinopoulos ◽  
Emmanouil Gkliatis
Keyword(s):  
General Anesthesia ◽  
Muscle Tone ◽  
Muscle Relaxants ◽  
Spastic Diplegia ◽  
Case Presentation ◽  
Neurosurgical Procedure ◽  
Dorsal Rhizotomy ◽  
Severe Spasticity ◽  
Larsson Syndrome ◽  
Rule Out

Introduction: Study of muscle tone in individuals with severe spasticity (Modified Asworth Scale – MAS:3) under general anesthesia can confirm or rule out the eventual necessity of the impending spasticity relieving ablative neurosurgery by observing the hypertonia reduction and passive range of motion expansion. Therefore, what we measure under muscle relaxants is practically a fixed deformity. Case Presentation: The study was performed on a girl with Sjögren-Larsson syndrome, presenting with icthyosis and spastic diplegia. Proposed intervention was Dorsal Rhizotomy. Under general anesthesia, with and without muscle relaxants, hypertonia was significantly reduced (MAS:1), but the angle of motion did not increase much. Conclusion: We decided not to perform such a neurosurgical procedure. In ambiguous situations, the proposed study can help in decision-making for spasticity treatment.

Low Morbidity and Mortality of Status Epilepticus in Children

PEDIATRICS ◽  
1989 ◽  
Vol 83 (3) ◽  
pp. 323-331
Author(s):  
Joseph Maytal ◽  
Shlomo Shinnar ◽  
Solomon L. Moshé ◽  
Luis A. Alvarez
Keyword(s):  
Status Epilepticus ◽  
Age Groups ◽  
Neurologic Disease ◽  
Neurologic Disorder ◽  
Patients Âgés ◽  
Symptomatic Group ◽  
Younger Age ◽  
The Status ◽  
Neurologic Sequelae ◽  
History Of

In an ongoing study of status epilepticus, 193 children with status epilepticus of varying causes have been followed up for a mean period of 13.2 months. Of these, 97 patients were recruited prospectively. The patients' ages ranged from 1 month to 18 years (mean, 5.0 years). The cause of the status epilepticus was classified as idiopathic in 46 cases, remote symptomatic in 45, febrile in 46, acute symptomatic in 45, and progressive neurologic in 11. The mortality and incidence of sequelae following status epilepticus was low and primarily a function of etiology. Seven children died within 3 months of having the seizure. New neurologic deficits were found in 17 (9.1%) of the 186 survivors. All of the deaths and 15 of the 17 sequelae occurred in the 56 children with acute or progressive neurologic insults. Only two of the 137 children with other causes sustained any new deficits (P < .001). Duration of the status epilepticus affected outcome only within the acute symptomatic group (P < .05). Neurologic sequelae occurred in 29% of infants younger than 1 year of age, 11% of children 1 to 3 years of age, and 6% of children older than 3 years of age. However, this was a reflection of the greater incidence of acute neurologic disease in the younger age groups. Within each cause, age did not affect outcome. Of the 193 children, 61 (32%) had a history of prior unprovoked seizures. Of the 125 surviving children with no history of prior unprovoked seizures, 37 (30%) had subsequent unprovoked seizures. It is concluded that the morbidity of aggressively treated status epilepticus in children, in the absence of an acute neurologic insult or progressive neurologic disorder, is low.

Two cases of Sjogren-Larsson syndrome in the same family

1986 ◽  
Vol 67 (6) ◽  
pp. 459-459
Author(s):  
I. K. Kuzmin ◽  
R. P. Gubar ◽  
V. V. Vasilevskaya
Keyword(s):  
Retinitis Pigmentosa ◽  
Autosomal Recessive ◽  
Epileptic Seizures ◽  
Spastic Diplegia ◽  
Variable Expression ◽  
High Penetrance ◽  
Larsson Syndrome

Sjоgren-Larsson syndrome is a hereditary disorder detected in the first months of a child's life. It is characterized by varying degrees of oligophrenia combined with spastic diplegia and congenital universal ichthyosis, and sometimes epileptic seizures, retinitis pigmentosa in the macula, dwarfism or giant growth, genital hypoplasia and anemia. Inheritance type is autosomal recessive with high penetrance and variable expression.

Jumonji domain containing 1C (JMJD1C) sequence variants in seven patients with autism spectrum disorder, intellectual disability and seizures

2020 ◽  
Vol 63 (4) ◽  
pp. 103850
Author(s):  
Anne Slavotinek ◽  
Johanna M. van Hagen ◽  
Louisa Kalsner ◽  
Shashidhar Pai ◽  
Laura Davis-Keppen ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Intellectual Disability ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Sequence Variants

scholarly journals A Novel ELP2 Compound Heterozygous Mutation in a Boy with Severe Intellectual Disability, Spastic Diplegia, Stereotypic Behavior and Review of the Current Literature

2020 ◽  
Vol 11 (5-6) ◽  
pp. 315-319
Author(s):  
Ayberk Turkyilmaz ◽  
Gunes Sager
Keyword(s):  
Intellectual Disability ◽  
Current Literature ◽  
Stereotypic Behavior ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Spastic Diplegia ◽  
Compound Heterozygous ◽  
Sequencing Analysis ◽  
Severe Intellectual Disability ◽  
Elongator Complex

The elongator complex consists of 6 highly conserved subunit proteins and is indispensable for various cellular functions, such as transcription elongation, histone acetylation, and tRNA modification. The elongator complex contains 2 subunits, each of which consists of 3 different proteins (encoded by the <i>ELP1–3</i> and <i>ELP4–6</i> genes). According to the OMIM database, <i>ELP2</i> gene variations have been reported to be associated with autosomal recessive mental retardation type 58. Here, we report a male patient with severe intellectual disability, spastic diplegia, and stereotypic behavior; in addition, we also provide a review of the current literature. Using whole-exome sequencing analysis, we detected a novel compound heterozygous variation in the <i>ELP2</i> gene. We present this case report to clarify the clinical findings of a very rare neurodevelopmental phenotype and to contribute new information to the current literature on genotype-phenotype correlations.

A Treatable Cause of Intellectual Disability and Autism in a Young Child

2020 ◽  
Vol 87 (10) ◽  
pp. 850-851
Author(s):  
Sangeetha Yoganathan ◽  
Suvasini Sharma ◽  
Mugil Varman ◽  
Mukul Malhotra ◽  
Mahalakshmi Chandran ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Young Child

scholarly journals Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

2021 ◽  
Author(s):  
Marjolein J. A. Weerts ◽  
Kristina Lanko ◽  
Francisco J. Guzmán-Vega ◽  
Adam Jackson ◽  
Reshmi Ramakrishnan ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Neurodevelopmental Disorder ◽  
Epileptic Activity ◽  
Language Delay ◽  
Global Developmental Delay ◽  
Sequence Variants ◽  
Loss Of Function ◽  
Phenotypic Spectrum

Abstract Purpose Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. Methods We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Results Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Conclusion Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome.

Spectrum of mutations and sequence variants in the FALDH gene in patients with Sjögren-Larsson syndrome

1998 ◽  
Vol 12 (6) ◽  
pp. 377-384 ◽  
Author(s):  
Anna Sillén ◽  
Ingrun Anton-Lamprecht ◽  
Cordula Braun-Quentin ◽  
Cornelia S. Kraus ◽  
Bekir Sitki Sayli ◽  
...  
Keyword(s):  
Sequence Variants ◽  
Larsson Syndrome

scholarly journals Attention Deficit Hyperactivity and Autism Spectrum Disorders as the Core Symptoms of AUTS2 Syndrome: Description of Five New Patients and Update of the Frequency of Manifestations and Genotype-Phenotype Correlation

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1360
Author(s):  
Carolina Sanchez-Jimeno ◽  
Fiona Blanco-Kelly ◽  
Fermina López-Grondona ◽  
Rebeca Losada-Del Pozo ◽  
Beatriz Moreno ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Attention Deficit ◽  
Autism Spectrum ◽  
Global Developmental Delay ◽  
Sequence Variants ◽  
Loss Of Function ◽  
Phenotype Correlation ◽  
Feeding Difficulties ◽  
Pathogenic Variants ◽  
Genotype Phenotype Correlation

Haploinsufficiency of AUTS2 has been associated with a syndromic form of neurodevelopmental delay characterized by intellectual disability, autistic features, and microcephaly, also known as AUTS2 syndrome. While the phenotype associated with large deletions and duplications of AUTS2 is well established, clinical features of patients harboring AUTS2 sequence variants have not been extensively described. In this study, we describe the phenotype of five new patients with AUTS2 pathogenic variants, three of them harboring loss-of-function sequence variants. The phenotype of the patients was characterized by attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) or autistic features and mild global developmental delay (GDD) or intellectual disability (ID), all in 4/5 patients (80%), a frequency higher than previously reported for ADHD and autistic features. Microcephaly and short stature were found in 60% of the patients; and feeding difficulties, generalized hypotonia, and ptosis, were each found in 40%. We also provide the aggregated frequency of the 32 items included in the AUTS2 syndrome severity score (ASSS) in patients currently reported in the literature. The main characteristics of the syndrome are GDD/ID in 98% of patients, microcephaly in 65%, feeding difficulties in 62%, ADHD or hyperactivity in 54%, and autistic traits in 52%. Finally, using the location of 31 variants from the literature together with variants from the five patients, we found significantly higher ASSS values in patients with pathogenic variants affecting the 3′ end of the gene, confirming the genotype-phenotype correlation initially described.

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