X-linked partial corpus callosum agenesis with mild intellectual disability: identification of a novel L1CAM pathogenic variant

Bousquet, Idriss; Bozon, Muriel; Castellani, Valérie; Touraine, Renaud; Piton, Amélie; Gérard, Bénédicte; Guibaud, Laurent; Sanlaville, Damien; Edery, Patrick; Saugier‐Veber, Pascale; Putoux, Audrey

doi:10.1007/s10048-020-00629-y

Cited by 5 publications

(9 citation statements)

References 26 publications

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“…Interestingly, these features have been recently described in five subjects harboring L1CAM mutations presenting with mild intellectual disability, even in the absence of adducted thumbs. 26 Moreover, four additional subjects with MASA syndrome reported in the literature presented similar brain abnormalities. 2 , 27 , 28 , 29 Considered the rarity of L1 disorders and the fact that subjects without obstructive hydrocephalus may not immediately be recognized as potential L1 mutation cases, we submit that this L1 phenotype may remain largely underdiagnosed.…”

Section: Discussionmentioning

confidence: 76%

“…The second phenotype, identified in one fetus presenting after birth with a MASA syndrome, was characterized by callosal dysgenesis, reduced white matter volume, and pontine hypoplasia. Interestingly, these features have been recently described in five subjects harboring L1CAM mutations presenting with mild intellectual disability, even in the absence of adducted thumbs 26 . Moreover, four additional subjects with MASA syndrome reported in the literature presented similar brain abnormalities 2,27–29 .…”

Section: Discussionmentioning

confidence: 77%

“…A positive family history was present in 7/10 (70%) cases. The median gestational age at MRI was 21.5 weeks (range [20][21][22][23][24][25][26][27][28][29][30][31][32]. Adducted thumb/clenched hands were noted in 8/10 (80%) cases.…”

Section: Resultsmentioning

confidence: 99%

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L1CAM variants cause two distinct imaging phenotypes on fetal MRI

Accogli

Goergen

Izzo

et al. 2021

Ann Clin Transl Neurol

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Data on fetal MRI in L1 syndrome are scarce with relevant implications for parental counseling and surgical planning. We identified two fetal MR imaging patterns in 10 fetuses harboring L1CAM mutations: the first, observed in 9 fetuses was characterized by callosal anomalies, diencephalosynapsis, and a distinct brainstem malformation with diencephalic–mesencephalic junction dysplasia and brainstem kinking. Cerebellar vermis hypoplasia, aqueductal stenosis, obstructive hydrocephalus, and pontine hypoplasia were variably associated. The second pattern observed in one fetus was characterized by callosal dysgenesis, reduced white matter, and pontine hypoplasia. The identification of these features should alert clinicians to offer a prenatal L1CAM testing.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 77%

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L1CAM variants cause two distinct imaging phenotypes on fetal MRI

Accogli

Goergen

Izzo

et al. 2021

Ann Clin Transl Neurol

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“…As a neuronal adhesion molecule, L1CAM mediates functions of cell–cell adhesion; growth-cone morphology; the guidance of neurite outgrowth, myelination, axon bundling, and pathfinding; long-term potentiation, neuronal cell survival and migration, and synaptogenesis ( Adle-Biassette et al, 2013 ). Mutations in L1CAM cause hydrocephalus with stenosis of the aqueduct of Sylvius and agenesis of the corpus callosum, hypoplasia of corticospinal tracts and the anterior cerebellar vermis, fusion of the thalami, and spastic paraplegia ( Willems et al, 1987 ; Bousquet et al, 2021 ). The precise mechanism of L1CAM defect–related ventricular dilation remains unclear, and the hypotheses are possibly due to L1CAM -mediated decrease in white matter elasticity, increased CSF pressure and ventricular vulnerability, abnormal development of the midline structure, and narrowing of the CSF pathway ( Kousi and Katsanis, 2016 ).…”

Section: Human Genetic Studies Of Hydrocephalusmentioning

confidence: 99%

Molecular Mechanisms and Risk Factors for the Pathogenesis of Hydrocephalus

Zhang

Guo

et al. 2022

Front. Genet.

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Hydrocephalus is a neurological condition due to the aberrant circulation and/or obstruction of cerebrospinal fluid (CSF) flow with consequent enlargement of cerebral ventricular cavities. However, it is noticed that a lot of patients may still go through symptomatic progression despite standard shunting procedures, suggesting that hydrocephalus is far more complicated than a simple CSF circulative/obstructive disorder. Growing evidence indicates that genetic factors play a fundamental role in the pathogenesis of some hydrocephalus. Although the genetic research of hydrocephalus in humans is limited, many genetic loci of hydrocephalus have been defined in animal models. In general, the molecular abnormalities involved in the pathogenesis of hydrocephalus include brain development and ependymal cell dysfunction, apoptosis, inflammation, free radical generation, blood flow, and cerebral metabolism. Moreover, recent studies have indicated that the molecular abnormalities relevant to aberrant cerebral glymphatic drainage turn into an attractive subject in the CSF circulation disorder. Furthermore, the prevalent risk factors could facilitate the development of hydrocephalus. In this review, we elicited some possible fundamental molecular mechanisms and facilitating risk factors involved in the pathogenesis of hydrocephalus, and aimed to widen the diagnosis and therapeutic strategies for hydrocephalus management. Such knowledge could be used to improve patient care in different ways, such as early precise diagnosis and effective therapeutic regimens.

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“…Since the main features of L1 syndrome include C orpus callosum hypoplasia, mental R etardation, A dducted thumbs, S pastic paraplegia, and H ydrocephalus, this condition is termed CRASH syndrome. (Gauntner et al, 2021 ) The incidence of this disease is 1/3000–25,000 in the live‐birth male babies, and the related pathogenic gene is the L1 cell adhesion molecule ( L1CAM ) gene (Bousquet et al, 2021 ). However, the pathogenetic mechanism underlying the L1 syndrome is yet to be elucidated, and the treatment requires shunting of the cerebrospinal fluid as needed (Itoh & Fushiki, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Analysis of L1CAM gene mutation and imaging appearance in three Chinese families with L1 syndrome: Three case reports

Gao

Zhao

et al. 2022

Molec Gen & Gen Med

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Background:The molecular mutations of the L1CAM gene and the imaging appearances of four fetuses with L1 syndrome from three independent Chinese families with a history of hydrocephalus were reported in this study. Two of the three are novel L1CAM variants. Methods:Results of clinical and imaging examinations of three Chinese families were collected. Fetal samples were collected by puncture, genomic DNA was extracted, whole-exome sequencing was performed, and the L1CAM gene mutation sites were verified by PCR and Sanger sequencing. Results:In this case report, we described the imaging appearance and investigated the mutations of the L1CAM gene in three Chinese families with a history of L1 syndrome; these included two nonsense mutations (c.262C>T and c.261C>G) and one splice-site mutation (c.524-1G>A). Two of these three are novel L1CAM variants: c.262C>T and c.261C>G. The results of the sonographic images of the affected fetuses showed severe hydrocephalus. Bilateral lateral ventricles were dilated in the fetuses with c.262C>T and c.261C>G mutations. The left ventricle was about 14 mm wide and the right was about 14 mm in the fetus with c.262C>T mutation. The left ventricle was about 24.9 mm wide and the right was about 23.9 mm in the fetus with c.261C>G mutation. The ultrasound examination of the fetus with c.524-1G>A mutation showed that the third ventricle (7.5 mm wide) was raised, and the fourth ventricle was communicated with the cisterna magna. The parents requested termination of the above pregnancy. Conclusion:The current study emphasizes the importance of combining family history, prenatal ultrasonography, and L1CAM mutation testing positive for the diagnosis of the L1 syndrome.

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X-linked partial corpus callosum agenesis with mild intellectual disability: identification of a novel L1CAM pathogenic variant

Cited by 5 publications

References 26 publications

L1CAM variants cause two distinct imaging phenotypes on fetal MRI

L1CAM variants cause two distinct imaging phenotypes on fetal MRI

Molecular Mechanisms and Risk Factors for the Pathogenesis of Hydrocephalus

Analysis of L1CAM gene mutation and imaging appearance in three Chinese families with L1 syndrome: Three case reports

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