Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information

X-linked lissencephaly(LISX1)

MedGen UID:
336286
Concept ID:
C1848199
Disease or Syndrome
Synonyms: DCX-Related Disorders; DCX-Related Lissencephaly; Lissencephaly and agenesis of corpus callosum; LISSENCEPHALY, X-LINKED, 1; LISX1; Subcortical laminar heterotopia, X-linked
Modes of inheritance:
X-linked inheritance
MedGen UID:
66838
Concept ID:
C0241764
Genetic Function
 
Gene: DCX
Cytogenetic location: Xq23
OMIM: 300067

Disease characteristics

Excerpted from the GeneReview: DCX-Related Disorders
DCX-related disorders include the neuronal migration disorders classic lissencephaly (formerly also known as lissencephaly type 1), usually in males; and subcortical band heterotopia (SBH, also called double cortex), primarily in females. Males with classic DCX-related lissencephaly typically have severe and global developmental delay, infantile-onset seizures (infantile spasms, West syndrome, focal and generalized seizures), and severe intellectual disability. In individuals with SBH, cognitive abilities range from normal to learning disabilities and/or severe intellectual disability. The majority of individuals with SBH present with focal or generalized seizures. Behavior problems may also be observed. In DCX-related lissencephaly and SBH the severity of the clinical manifestation correlates with the degree of the underlying brain malformation.  [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  GeneReview Scope  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Ute Hehr  |  Goekhan Uyanik  |  Ludwig Aigner, et. al.   view full author information

Additional descriptions

From 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. DCX mutations cause classic lissencephaly with mental retardation in hemizygous males and a milder phenotype known as subcortical band heterotopia in females, sometimes in the same family. The subcortical lamina heterotopia found in heterozygous females is also referred to as 'double cortex' (DC) syndrome (des Portes et al., 1997). There are several X-linked loci that affect neuronal migration, including the Aicardi locus (304050).  http://www.omim.org/entry/300067
From GHR
Isolated lissencephaly sequence (ILS) is a condition that affects brain development before birth. Normally, the cells that make up the exterior of the brain (cerebral cortex) are well-organized, multi-layered, and arranged into many folds and grooves (gyri). In people with ILS, the cells of the cerebral cortex are disorganized, and the brain surface is abnormally smooth with an absence (agyria) or reduction (pachygyria) of folds and grooves. In most cases, these abnormalities impair brain growth, causing the brain to be smaller than normal (microcephaly). This underdevelopment of the brain causes severe intellectual disability, delayed development, and recurrent seizures (epilepsy) in individuals with ILS. More than 90 percent of individuals with ILS develop epilepsy, often within the first year of life. Up to 80 percent of infants with ILS have a type of seizure called infantile spasms, these seizures can be severe enough to cause brain dysfunction (epileptic encephalopathy). After the first months of life, most children with ILS develop a variety of seizure types, including persisting infantile spasms, short periods of loss of consciousness (absence seizures); sudden episodes of weak muscle tone (drop attacks); rapid, uncontrolled muscle jerks (myoclonic seizures); and episodes of muscle rigidity, convulsions, and loss of consciousness (tonic-clonic seizures). Infants with ILS may have poor muscle tone (hypotonia) and difficulty feeding, which leads to poor growth overall. Hypotonia also affects the muscles used for breathing, which often causes breathing problems that can lead to a life-threatening bacterial lung infection known as aspiration pneumonia. Children with ILS often develop muscle stiffness (spasticity) in their arms and legs and an abnormal side-to-side curvature of the spine (scoliosis). Rarely, the muscle stiffness will progress to paralysis (spastic paraplegia). Individuals with ILS cannot walk and rarely crawl. Most children with ILS do not develop communication skills.  http://ghr.nlm.nih.gov/condition/isolated-lissencephaly-sequence

Clinical features

Micropenis
MedGen UID:
504321
Concept ID:
CN000054
Finding
Abnormally small `penis` (FMA:9707). At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.
Ataxia
MedGen UID:
504767
Concept ID:
CN001146
Finding
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Motor delay
MedGen UID:
504779
Concept ID:
CN001164
Finding
A type of `Developmental delay` (HP:0001263) characterized by a delay in acquiring motor skills.
Pachygyria
MedGen UID:
504794
Concept ID:
CN001193
Finding
A congenital abnormality of the cerebral hemisphere chacterized by unusually thick gyrations (convolutions) of the cerebral cortex.
Lissencephaly
MedGen UID:
504808
Concept ID:
CN001227
Finding
A congenital absence of the convolutions of the cerebral cortex and a poorly formed sylvian fissure.
Muscular hypotonia
MedGen UID:
504768
Concept ID:
CN001147
Finding
Muscular hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. Hypotonia is characterized by a diminished resistance to passive stretching.
Muscular hypotonia of the trunk
MedGen UID:
446966
Concept ID:
CN007863
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.

Recent clinical studies

Etiology

Beguin S, Crépel V, Aniksztejn L, Becq H, Pelosi B, Pallesi-Pocachard E, Bouamrane L, Pasqualetti M, Kitamura K, Cardoso C, Represa A
Cereb Cortex 2013 Jun;23(6):1484-94. Epub 2012 May 24 doi: 10.1093/cercor/bhs138. [Epub ahead of print] PMID: 22628459
Leger PL, Souville I, Boddaert N, Elie C, Pinard JM, Plouin P, Moutard ML, des Portes V, Van Esch H, Joriot S, Renard JL, Chelly J, Francis F, Beldjord C, Bahi-Buisson N
Neurogenetics 2008 Oct;9(4):277-85. Epub 2008 Aug 7 doi: 10.1007/s10048-008-0141-5. [Epub ahead of print] PMID: 18685874
Kato M, Das S, Petras K, Kitamura K, Morohashi K, Abuelo DN, Barr M, Bonneau D, Brady AF, Carpenter NJ, Cipero KL, Frisone F, Fukuda T, Guerrini R, Iida E, Itoh M, Lewanda AF, Nanba Y, Oka A, Proud VK, Saugier-Veber P, Schelley SL, Selicorni A, Shaner R, Silengo M, Stewart F, Sugiyama N, Toyama J, Toutain A, Vargas AL, Yanazawa M, Zackai EH, Dobyns WB
Hum Mutat 2004 Feb;23(2):147-59. doi: 10.1002/humu.10310. PMID: 14722918
Sherr EH
Curr Opin Pediatr 2003 Dec;15(6):567-71. PMID: 14631200
Leventer RJ, Mills PL, Dobyns WB
Am J Med Genet 2000 Fall;97(3):213-20. doi: 10.1002/1096-8628(200023)97:3<213::AID-AJMG1039>3.0.CO;2-W. PMID: 11449490

Diagnosis

Inoue T, Kawawaki H, Kuki I, Nabatame S, Tomonoh Y, Sukigara S, Horino A, Nukui M, Okazaki S, Tomiwa K, Kimura-Ohba S, Inoue T, Hirose S, Shiomi M, Itoh M
J Neurol Sci 2013 Apr 15;327(1-2):65-72. Epub 2013 Feb 16 doi: 10.1016/j.jns.2013.01.038. [Epub ahead of print] PMID: 23422026
Okazaki S, Ohsawa M, Kuki I, Kawawaki H, Koriyama T, Ri S, Ichiba H, Hai E, Inoue T, Nakamura H, Goto Y, Tomiwa K, Yamano T, Kitamura K, Itoh M
Acta Neuropathol 2008 Oct;116(4):453-62. Epub 2008 May 6 doi: 10.1007/s00401-008-0382-2. [Epub ahead of print] PMID: 18458920
Halac I, Habiby R, Curran J, Zimmerman D
J Pediatr Endocrinol Metab 2006 Jul;19(7):955-7. PMID: 16995578
Hahn A, Gross C, Uyanik G, Hehr U, Hügens-Penzel M, Alzen G, Neubauer BA
Neuropediatrics 2004 Jun;35(3):202-5. doi: 10.1055/s-2004-817955. PMID: 15248105
Panda S, Tripathi M, Jain S, Sharma P
Neurol India 2003 Sep;51(3):392-3. PMID: 14652450

Therapy

Saito T, Hanai S, Takashima S, Nakagawa E, Okazaki S, Inoue T, Miyata R, Hoshino K, Akashi T, Sasaki M, Goto Y, Hayashi M, Itoh M
Cereb Cortex 2011 Mar;21(3):588-96. Epub 2010 Jul 12 doi: 10.1093/cercor/bhq125. [Epub ahead of print] PMID: 20624841
Kato M, Das S, Petras K, Kitamura K, Morohashi K, Abuelo DN, Barr M, Bonneau D, Brady AF, Carpenter NJ, Cipero KL, Frisone F, Fukuda T, Guerrini R, Iida E, Itoh M, Lewanda AF, Nanba Y, Oka A, Proud VK, Saugier-Veber P, Schelley SL, Selicorni A, Shaner R, Silengo M, Stewart F, Sugiyama N, Toyama J, Toutain A, Vargas AL, Yanazawa M, Zackai EH, Dobyns WB
Hum Mutat 2004 Feb;23(2):147-59. doi: 10.1002/humu.10310. PMID: 14722918
Ross ME, Allen KM, Srivastava AK, Featherstone T, Gleeson JG, Hirsch B, Harding BN, Andermann E, Abdullah R, Berg M, Czapansky-Bielman D, Flanders DJ, Guerrini R, Motté J, Mira AP, Scheffer I, Berkovic S, Scaravilli F, King RA, Ledbetter DH, Schlessinger D, Dobyns WB, Walsh CA
Hum Mol Genet 1997 Apr;6(4):555-62. PMID: 9097958

Prognosis

Miyata R, Hayashi M, Miyai K, Akashi T, Kato M, Kohyama J
Brain Dev 2009 Jun;31(6):456-60. Epub 2008 Oct 7 doi: 10.1016/j.braindev.2008.08.008. [Epub ahead of print] PMID: 18842366
Leger PL, Souville I, Boddaert N, Elie C, Pinard JM, Plouin P, Moutard ML, des Portes V, Van Esch H, Joriot S, Renard JL, Chelly J, Francis F, Beldjord C, Bahi-Buisson N
Neurogenetics 2008 Oct;9(4):277-85. Epub 2008 Aug 7 doi: 10.1007/s10048-008-0141-5. [Epub ahead of print] PMID: 18685874
Kato M, Dobyns WB
J Child Neurol 2005 Apr;20(4):392-7. PMID: 15921244
Uyanik G, Aigner L, Martin P, Gross C, Neumann D, Marschner-Schäfer H, Hehr U, Winkler J
Neurology 2003 Jul 22;61(2):232-5. PMID: 12874405
Gleeson JG, Allen KM, Fox JW, Lamperti ED, Berkovic S, Scheffer I, Cooper EC, Dobyns WB, Minnerath SR, Ross ME, Walsh CA
Cell 1998 Jan 9;92(1):63-72. PMID: 9489700

Clinical prediction guides

Leger PL, Souville I, Boddaert N, Elie C, Pinard JM, Plouin P, Moutard ML, des Portes V, Van Esch H, Joriot S, Renard JL, Chelly J, Francis F, Beldjord C, Bahi-Buisson N
Neurogenetics 2008 Oct;9(4):277-85. Epub 2008 Aug 7 doi: 10.1007/s10048-008-0141-5. [Epub ahead of print] PMID: 18685874
Hahn A, Gross C, Uyanik G, Hehr U, Hügens-Penzel M, Alzen G, Neubauer BA
Neuropediatrics 2004 Jun;35(3):202-5. doi: 10.1055/s-2004-817955. PMID: 15248105
Bonneau D, Toutain A, Laquerrière A, Marret S, Saugier-Veber P, Barthez MA, Radi S, Biran-Mucignat V, Rodriguez D, Gélot A
Ann Neurol 2002 Mar;51(3):340-9. PMID: 11891829
Dobyns WB, Berry-Kravis E, Havernick NJ, Holden KR, Viskochil D
Am J Med Genet 1999 Oct 8;86(4):331-7. PMID: 10494089
Gleeson JG, Allen KM, Fox JW, Lamperti ED, Berkovic S, Scheffer I, Cooper EC, Dobyns WB, Minnerath SR, Ross ME, Walsh CA
Cell 1998 Jan 9;92(1):63-72. PMID: 9489700

Recent systematic reviews

Okazaki S, Ohsawa M, Kuki I, Kawawaki H, Koriyama T, Ri S, Ichiba H, Hai E, Inoue T, Nakamura H, Goto Y, Tomiwa K, Yamano T, Kitamura K, Itoh M
Acta Neuropathol 2008 Oct;116(4):453-62. Epub 2008 May 6 doi: 10.1007/s00401-008-0382-2. [Epub ahead of print] PMID: 18458920

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...