Format

Send to:

Choose Destination

Links from PubMed

Lissencephaly, X-linked(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
Source: HPO
A mode of inheritance that is observed for traits related to a gene encoded on the X chromosome.
 
Gene (location): DCX (Xq23)
OMIM®: 300067
Orphanet: ORPHA2148

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]
Authors:
Ute Hehr  |  Gökhan 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

Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Micropenis
MedGen UID:
78603
Concept ID:
C0266435
Congenital Abnormality
Abnormally small penis. 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.
Postnatal growth retardation
MedGen UID:
395343
Concept ID:
C1859778
Finding
Slow or limited growth after birth.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Sign or Symptom
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).
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Seizure Disorders
MedGen UID:
4506
Concept ID:
C0014544
Disease or Syndrome
Epilepsy is a brain disorder that causes people to have recurring seizures. The seizures happen when clusters of nerve cells, or neurons, in the brain send out the wrong signals. People may have strange sensations and emotions or behave strangely. They may have violent muscle spasms or lose consciousness. Epilepsy has many possible causes, including illness, brain injury, and abnormal brain development. In many cases, the cause is unknown. Doctors use brain scans and other tests to diagnose epilepsy. It is important to start treatment right away. There is no cure for epilepsy, but medicines can control seizures for most people. When medicines are not working well, surgery or implanted devices such as vagus nerve stimulators may help. Special diets can help some children with epilepsy. NIH: National Institute of Neurological Disorders and Stroke.
Intellectual functioning disability
MedGen UID:
7544
Concept ID:
C0025362
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
Muscle Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Corpus callosum agenesis
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
Lissencephaly
MedGen UID:
78604
Concept ID:
C0266463
Finding
A congenital absence of the convolutions of the cerebral cortex and a poorly formed sylvian fissure.
Macrogyria
MedGen UID:
120579
Concept ID:
C0266483
Congenital Abnormality
Increased size of cerebral gyri, often associated with a moderate reduction in the number of sulci of the cerebrum.
Cognitive impairment
MedGen UID:
90932
Concept ID:
C0338656
Mental or Behavioral Dysfunction
a condition where a person has problems with the ability to think and learn
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Muscle Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Muscular hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
A diminution of the skeletal muscle tone marked by a diminished resistance to passive stretching.
Axial hypotonia
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.

Term Hierarchy

Follow this link to review classifications for Lissencephaly, X-linked in Orphanet.

Recent clinical studies

Etiology

Ito K, Nakata Y, Matsuda H, Sugai K, Watanabe M, Kamiya K, Kimura Y, Shigemoto Y, Okazaki M, Sasaki M, Sato N
Brain Dev 2014 Aug;36(7):578-84. Epub 2013 Aug 16 doi: 10.1016/j.braindev.2013.07.017. [Epub ahead of print] PMID: 23958594
Capra V, Mirabelli-Badenier M, Stagnaro M, Rossi A, Tassano E, Gimelli S, Gimelli G
BMC Med Genet 2012 Oct 4;13:93. doi: 10.1186/1471-2350-13-93. [Epub ahead of print] PMID: 23035971Free PMC Article
Merwick A, O'Brien M, Delanty N
Epilepsia 2012 Sep;53 Suppl 4:81-91. doi: 10.1111/j.1528-1167.2012.03617.x. PMID: 22946725
Lockrow JP, Holden KR, Dwivedi A, Matheus MG, Lyons MJ
J Child Neurol 2012 Jun;27(6):791-5. Epub 2011 Dec 21 doi: 10.1177/0883073811425972. [Epub ahead of print] PMID: 22190508
Spencer-Smith M, Leventer R, Jacobs R, Luca CD, Anderson V
Dev Med Child Neurol 2009 Nov;51(11):909-16. Epub 2009 Mar 31 doi: 10.1111/j.1469-8749.2009.03309.x. [Epub ahead of print] PMID: 19416314

Diagnosis

Wakerley BR, Wilder-Smith EP, Yuki N
Pract Neurol 2015 Jun;15(3):236-9. Epub 2015 Apr 27 doi: 10.1136/practneurol-2015-001084. [Epub ahead of print] PMID: 25918431
Wakerley BR, Yuki N
Pract Neurol 2015 Apr;15(2):90-9. Epub 2014 Sep 19 doi: 10.1136/practneurol-2014-000937. [Epub ahead of print] PMID: 25239628
Nalbantoglu M, Erturk-Cetin O, Gozubatik-Celik G, Demirbilek V
Pediatr Neurol 2014 Jul;51(1):178-80. Epub 2014 Mar 4 doi: 10.1016/j.pediatrneurol.2014.02.018. [Epub ahead of print] PMID: 24810876
Chen CP, Chang TY, Guo WY, Wu PC, Wang LK, Chern SR, Wu PS, Su JW, Chen YT, Chen LF, Wang W
Gene 2013 Dec 10;532(1):152-9. Epub 2013 Sep 19 doi: 10.1016/j.gene.2013.09.044. [Epub ahead of print] PMID: 24055730
Quélin C, Saillour Y, Souville I, Poirier K, N'guyen-Morel MA, Vercueil L, Millisher-Bellaiche AE, Boddaert N, Dubois F, Chelly J, Beldjord C, Bahi-Buisson N
Neurogenetics 2012 Nov;13(4):367-73. Epub 2012 Jul 26 doi: 10.1007/s10048-012-0339-4. [Epub ahead of print] PMID: 22833188

Therapy

Østergaard JR, Graakjær J, Brandt C, Birkebæk NH
Eur J Med Genet 2012 Jan;55(1):22-6. Epub 2011 Oct 24 doi: 10.1016/j.ejmg.2011.09.004. [Epub ahead of print] PMID: 22085993
Cukiert A, Mariani PP, Burattini JA, Cukiert CM, Forster C, Baise C, Argentoni-Baldochi M, Mello V
Epilepsia 2009 Dec;50(12):2667-9. Epub 2009 Aug 8 doi: 10.1111/j.1528-1167.2009.02255.x. [Epub ahead of print] PMID: 19674051
Koutsouraki E, Timplalexi G, Papadopoulou Z, Costa V, Baloyannis S
Int J Neurosci 2008 Mar;118(3):343-8. doi: 10.1080/00207450601050261. PMID: 18300007

Prognosis

Adams DJ, Clark DA
Pediatr Clin North Am 2015 Apr;62(2):411-26. Epub 2015 Jan 22 doi: 10.1016/j.pcl.2014.11.005. [Epub ahead of print] PMID: 25836705
Wakerley BR, Yuki N
Pract Neurol 2015 Apr;15(2):90-9. Epub 2014 Sep 19 doi: 10.1136/practneurol-2014-000937. [Epub ahead of print] PMID: 25239628
Bahi-Buisson N, Souville I, Fourniol FJ, Toussaint A, Moores CA, Houdusse A, Lemaitre JY, Poirier K, Khalaf-Nazzal R, Hully M, Leger PL, Elie C, Boddaert N, Beldjord C, Chelly J, Francis F; SBH-LIS European Consortium
Brain 2013 Jan;136(Pt 1):223-44. doi: 10.1093/brain/aws323. PMID: 23365099Free PMC Article
Mokánszki A, Körhegyi I, Szabó N, Bereg E, Gergev G, Balogh E, Bessenyei B, Sümegi A, Morris-Rosendahl DJ, Sztriha L, Oláh E
J Child Neurol 2012 Dec;27(12):1534-40. Epub 2012 Mar 8 doi: 10.1177/0883073811436326. [Epub ahead of print] PMID: 22408144
Lockrow JP, Holden KR, Dwivedi A, Matheus MG, Lyons MJ
J Child Neurol 2012 Jun;27(6):791-5. Epub 2011 Dec 21 doi: 10.1177/0883073811425972. [Epub ahead of print] PMID: 22190508

Clinical prediction guides

Kim T, Bershteyn M, Wynshaw-Boris A
Nucleus 2014 Sep-Oct;5(5):391-5. doi: 10.4161/nucl.36300. PMID: 25482192Free PMC Article
Ito K, Nakata Y, Matsuda H, Sugai K, Watanabe M, Kamiya K, Kimura Y, Shigemoto Y, Okazaki M, Sasaki M, Sato N
Brain Dev 2014 Aug;36(7):578-84. Epub 2013 Aug 16 doi: 10.1016/j.braindev.2013.07.017. [Epub ahead of print] PMID: 23958594
Bahi-Buisson N, Souville I, Fourniol FJ, Toussaint A, Moores CA, Houdusse A, Lemaitre JY, Poirier K, Khalaf-Nazzal R, Hully M, Leger PL, Elie C, Boddaert N, Beldjord C, Chelly J, Francis F; SBH-LIS European Consortium
Brain 2013 Jan;136(Pt 1):223-44. doi: 10.1093/brain/aws323. PMID: 23365099Free PMC Article
Mokánszki A, Körhegyi I, Szabó N, Bereg E, Gergev G, Balogh E, Bessenyei B, Sümegi A, Morris-Rosendahl DJ, Sztriha L, Oláh E
J Child Neurol 2012 Dec;27(12):1534-40. Epub 2012 Mar 8 doi: 10.1177/0883073811436326. [Epub ahead of print] PMID: 22408144
Lockrow JP, Holden KR, Dwivedi A, Matheus MG, Lyons MJ
J Child Neurol 2012 Jun;27(6):791-5. Epub 2011 Dec 21 doi: 10.1177/0883073811425972. [Epub ahead of print] PMID: 22190508

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...