Lissencephaly type 1 due to doublecortin gene mutation

General Information (adopted from Orphanet):

Synonyms, Signs: DOUBLE CORTEX SYNDROME, INCLUDED
DC SYNDROME, INCLUDED
LISSENCEPHALY AND AGENESIS OF CORPUS CALLOSUM SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED, INCLUDED
SUBCORTICAL BAND HETEROTOPIA, X-LINKED, INCLUDED
SCLH, INCLUDED
SBH, INCLUDED
LISX1
XLIS
X-linked lissencephaly type 1
Number of Symptoms 23
OrphanetNr: 2148
OMIM Id: 300067
ICD-10: Q04.3
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: X-linked recessive
[Orphanet]
Age of onset: Neonatal
Infancy
Childhood
Adolescent
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Classic lissencephaly
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease
X-linked syndromic intellectual deficit
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
(HPO:0000054) Micropenis 257 / 7739
2
(HPO:0000639) Nystagmus 555 / 7739
3
(HPO:0001250) Seizures Very frequent [Orphanet] 1245 / 7739
4
(HPO:0001276) Hypertonia Frequent [Orphanet] 317 / 7739
5
(HPO:0001251) Ataxia 413 / 7739
6
(HPO:0001260) Dysarthria 329 / 7739
7
(HPO:0001270) Motor delay 322 / 7739
8
(HPO:0001249) Intellectual disability 1089 / 7739
9
(HPO:0008897) Postnatal growth retardation 113 / 7739
10
(HPO:0004325) Decreased body weight Frequent [Orphanet] 492 / 7739
11
(HPO:0008936) Muscular hypotonia of the trunk 77 / 7739
12
(HPO:0001252) Muscular hypotonia Frequent [Orphanet] 990 / 7739
13
(HPO:0001522) Death in infancy 275 / 7739
14
(HPO:0001302) Pachygyria 60 / 7739
15
(HPO:0003593) Infantile onset 249 / 7739
16
(HPO:0001274) Agenesis of corpus callosum 142 / 7739
17
(HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 949 / 7739
18
(OMIM) Subcortical band or laminar heterotopia (in female carriers) 1 / 7739
19
(HPO:0001417) X-linked inheritance 173 / 7739
20
(HPO:0003829) Incomplete penetrance 85 / 7739
21
(OMIM) Limb spasticity 3 / 7739
22
(OMIM) Malformation of the insula 1 / 7739
23
(HPO:0001339) Lissencephaly 30 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Lissencephaly ('smooth brain') results from migrational arrest of cortical neurons short of their normal destination, and can result in profound mental retardation and seizures. In X-linked lissencephaly-1, affected males generally have more a severe phenotype compared to females. ...
Clinical Description OMIM Berry-Kravis and Israel (1994) reported a family in which 5 male infants in 2 generations had lissencephaly inherited in an X-linked pattern. All the affected infants had intractable seizures, severe retardation, growth failure, and microphallus, and died during ...
Genotype-Phenotype Correlations OMIM By direct DNA sequencing of the LIS1 and DCX genes in 25 children with sporadic lissencephaly and no deletion of the LIS1 gene by FISH, Pilz et al. (1998) identified LIS1 mutations in 8 (32%) patients and DCX ...
Molecular genetics OMIM In affected individuals from 3 unrelated families with LISX or subcortical laminar heterotopia and a girl with subcortical laminar heterotopia and pachygyria, des Portes et al. (1998) identified mutations in the DCX gene (300121.0001-300121.0004). Gleeson et al. (1998) ...
Diagnosis GeneReviews DCX-related conditions include the neuronal migration disorders:...
Clinical Description GeneReviews Males. DCX-related classic lissencephaly usually manifests with early and profound cognitive and language impairment, cerebral palsy, and epileptic seizures. Individuals with severe classic lissencephaly and survival into adulthood have been reported anecdotally; however, life span would be expected to be shortened. Severity of symptoms usually correlates with the degree of the underlying brain malformation. ...
Genotype-Phenotype Correlations GeneReviews In general, there is a direct correlation between the severity of the cortical malformation and the resulting phenotype. More importantly and consistent with X-linked dominant inheritance, DCX mutations in hemizygous males predominantly result in classic lissencephaly, while DCX mutations in heterozygous females predominantly result in SBH. In addition, a slight effect of the type and location of the DCX mutation on the resulting severity of the brain malformation for both SBH and classic lissencephaly has been suggested [Leventer 2005]. ...
Differential Diagnosis GeneReviews LIS1-associated lissencephaly/subcortical band heterotopia. Mutations in DCX together with mutations in LIS1 (also termed PAFAH1B1) are the major genetic cause of nonsyndromic classic lissencephaly in males and of SBH in females [Kato & Dobyns 2003]. LIS1-associated lissencephaly is more prominent in the posterior regions of the brain, showing a posterior to anterior (P>A) gradient. In contrast, DCX-related lissencephaly presents with an A>P gradient. ...
Management GeneReviews To establish the individual clinical manifestation of a DCX-related disorder, the following evaluations are recommended:...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....