X-linked lissencephaly with absent corpus callosum and ambiguous genitalia

Dobyns, William B.; Berry‐Kravis, Elizabeth; Havernick, Nancy J.; Holden, Kenton R.; Viskochil, David

doi:10.1002/(sici)1096-8628(19991008)86:4<331::aid-ajmg7>3.0.co;2-p

Cited by 127 publications

(81 citation statements)

References 13 publications

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“…Lastly, temporal-predominant thin LIS with ACC and abnormal white matter is caused by mutations in ARX. This is one of the few syndromic forms of LIS, causing X-linked LIS with abnormal genitalia or XLAG [Berry-Kravis and Israel 1994; Dobyns et al, 1999a; Kato et al, 2004; Kitamura et al, 2002]. …”

Section: Discussionmentioning

confidence: 99%

Lissencephaly: Expanded imaging and clinical classification

Donato

Chiari

Mirzaa

et al. 2017

American J of Med Genetics Pt A

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Lissencephaly (“smooth brain”, LIS) is a malformation of cortical development associated with deficient neuronal migration and abnormal formation of cerebral convolutions or gyri. The LIS spectrum includes agyria, pachygyria, and subcortical band heterotopia. Our first classification of LIS and subcortical band heterotopia (SBH) was developed to distinguish between the first two genetic causes of LIS – LIS1 (PAFAH1B1) and DCX. However, progress in molecular genetics has led to identification of 19 LIS-associated genes, leaving the existing classification system insufficient to distinguish the increasingly diverse patterns of LIS. To address this challenge, we reviewed clinical, imaging and molecular data on 188 patients with LIS-SBH ascertained during the last five years, and reviewed selected archival data on another ~1,400 patients. Using these data plus published reports, we constructed a new imaging based classification system with 21 recognizable patterns that reliably predict the most likely causative genes. These patterns do not correlate consistently with the clinical outcome, leading us to also develop a new scale useful for predicting clinical severity and outcome. Taken together, our work provides new tools that should prove useful for clinical management and genetic counselling of patients with LIS-SBH (imaging and severity based classifications), and guidance for prioritizing and interpreting genetic testing results (imaging based classification).

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Section: Discussionmentioning

confidence: 99%

Lissencephaly: Expanded imaging and clinical classification

Donato

Chiari

Mirzaa

et al. 2017

American J of Med Genetics Pt A

Self Cite

136

138

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“…Arx genetic defects have been found in various early life epileptic encephalopathies, including West syndrome, and may or may not show pronounced structural brain and other abnormalities, as in X-linked lissencephaly with abnormal genitalia (XLAG) (Dobyns et al 1999; Kato et al 2003; Stromme et al 2002). Neuropathological features of XLAG include loss of cortical interneurons, gliosis and heterotopic neurons in the periventricular white matter, corpus callosum agenesis, disorganization and atrophy of the striatum and diencephalon (Bonneau et al 2002).…”

Section: West Syndrome and Infantile Spasmsmentioning

confidence: 99%

Pathogenesis and new candidate treatments for infantile spasms and early life epileptic encephalopathies: A view from preclinical studies

Galanopoulou

Moshé

2015

Neurobiology of Disease

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Early onset and infantile epileptic encephalopathies (EIEEs) are usually associated with medically intractable or difficult to treat epileptic seizures and prominent cognitive, neurodevelopmental and behavioral consequences. EIEEs have numerous etiologies that contribute to the inter- and intra-syndromic phenotypic variability. Etiologies include structural and metabolic or genetic etiologies although a significant percentage is of unknown cause. The need to better understand their pathogenic mechanisms and identify better therapies has driven the development of animal models of EIEEs. Several rodent models of infantile spasms have emerged that recapitulate various aspects of the disease. The acute models manifest epileptic spasms after induction and include the NMDA rat model, the NMDA model with prior prenatal betamethasone or perinatal stress exposure, and the γ-butyrolactone induced spasms in a mouse model of Down syndrome. The chronic models include the tetrodotoxin rat model, the aristaless related homeobox X-linked (Arx) mouse models and the multiple-hit rat model of infantile spasms. We will discuss the main features and findings from these models on target mechanisms and emerging therapies. Genetic models have also provided interesting data on the pathogenesis of Dravet syndrome and proposed new therapies for testing. The genetic associations of many of the EIEEs have also been tested in rodent models as to their pathogenicity. Finally, several models have tested the impact of subclinical epileptiform discharges on brain function. The impact of these advances in animal modeling for therapy development will be discussed.

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“…Since then, several other mutations have been described and broadened the spectrum of phenotypes resulting from ARX mutations (Figure 1). These phenotypes can be divided into two groups: (1) a malformation group, which includes X-linked lissencephaly associated with abnormal genitalia (XLAG) (OMIM 300215) (Dobyns et al, 1999; Ogata et al, 2000; Kitamura et al, 2002), hydranencephaly and abnormal genitalia (HYD-AG) (OMIM 300215) and Proud syndrome (OMIM 300004) (Kato et al, 2004); and (2) a non-malformation group including non-syndromic XLMR (Bienvenu et al, 2002), Partington syndrome (PRTS) (OMIM 309510) (Frints et al, 2002; Strømme et al, 2002), various forms of epilepsy including West syndrome (Strømme et al, 2002; Kato et al, 2003), X-linked myoclonic seizures, spasticity and intellectual disability (XMESID) (OMIM 308350) (Scheffer et al, 2002; Strømme et al, 2002), idiopathic infantile epileptic-dyskinetic encephalopathy (IEDE) (OMIM 308350) (Guerrini et al, 2007) and early infantile epileptic encephalopathy with suppression-burst pattern (EIEE or Ohtahara's syndrome) (OMIM 308350) (Kato et al, 2007) (see Table 1 for a description of these syndromes).…”

Section: Arx Mutations In Humanmentioning

confidence: 99%

Mutations in ARX result in several defects involving GABAergic neurons

Friocourt

Parnavelas

2010

Front. Cell. Neurosci.

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Genetic investigations of X-linked mental retardation have demonstrated the implication of ARX in a wide spectrum of disorders extending from phenotypes with severe neuronal migration defects, such as lissencephaly, to mild or moderate forms of mental retardation without apparent brain abnormalities, but with associated features of dystonia and epilepsy. These investigations have in recent years directed attention to the role of this gene in brain development. Analysis of its spatio-temporal localization profile revealed expression in telencephalic structures at all stages of development, mainly restricted to populations of GABA-containing neurons. Furthermore, studies of the effects of ARX loss of function either in humans or in lines of mutant mice revealed varying defects, suggesting multiple roles of this gene during development. In particular, Arx has been shown to contribute to almost all fundamental processes of brain development: patterning, neuronal proliferation and migration, cell maturation and differentiation, as well as axonal outgrowth and connectivity. In this review, we will present and discuss recent findings concerning the role of ARX in brain development and how this information will be useful to better understand the pathophysiological mechanisms of mental retardation and epilepsy associated with ARX mutations.

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X-linked lissencephaly with absent corpus callosum and ambiguous genitalia

Cited by 127 publications

References 13 publications

Lissencephaly: Expanded imaging and clinical classification

Lissencephaly: Expanded imaging and clinical classification

Pathogenesis and new candidate treatments for infantile spasms and early life epileptic encephalopathies: A view from preclinical studies

Mutations in ARX result in several defects involving GABAergic neurons

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