WikiJournal Preprints/Microlissencephaly: a narrative review
Author: Anon until publication
Anon until publication.
Microlissencephaly (MLIS) is a rare congenital brain disorder that combines severe microcephaly (small head) with lissencephaly (smooth brain surface due to absent sulci and gyri) (Figure 1). MLIS is a heterogeneous disorder, having many different causes and a variable clinical course. It is a malformation of cortical development (MCD) that occurs due to the failure of neuronal migration between the third and fifth month of gestation as well as stem cell population abnormalities (either increased apoptosis or decreased production).
The combination of lissencephaly with severe congenital microcephaly is designated as MLIS only when the cortex is abnormally thick. If such combination exists with a normal cortical thickness (2.5 to 3 mm), it is known as "microcephaly with simplified gyral pattern" (MSGP). Both MLIS and MSGP have a much more severe clinical course than microcephaly alone. Prior to the year 2000, the term “microlissencephaly” was used to designate both MLIS and MSGP. Both MLIS and MSGP result from either decreased stem cell proliferation or increased apoptosis in the germinal zone of the cerebral cortex.
Figure 2 | STRING protein-protein interaction networks of proteins associated with MLIS. Tubulin proteins are grouped together. No association among CIT, DMRTA2, WDR62, WDR81 (right side) and the rest is detected. RNU4ATAC protein, mutated in MOPD1, is not found in STRING.
The genetic basis and pathophysiology of MLIS are still not completely understood. Most cases of MLIS are described in consanguineous families suggesting an autosomal recessive inheritance. Numerous genes have been found to be associated with MLIS (Table 1). The physical and functional interaction between proteins associated with microlissencephaly was analyzed using STRING database "http://version10.string-db.org/" (Figure 2).
Moreover, human NDE1 mutations and mouse Nde1 loss lead to cortical lamination deficits, which, together with reduced neuronal production cause MLIS. Homozygous frameshift mutations in NDE1 gene was found to cause MLIS with up to 90% reduction in brain mass and seizures starting early in life.
Some other associated genes include KATNB1 (Katanin p80) and WDR62. Katanin, a microtubule-severing enzyme, is composed of a catalytic, p60 (KATNA1), and a regulatory, p80 (KATNB1), subunit. p80/KATNB1 binds to p60 and targets it to subcellular structures including the centrosome, further mediating its interactions with dynein, LIS1, and NDEL1. In developing neurons, Katanin localizes to microtubules and centrosomes and is essential for microtubule shortening and release. Katanin functions in cell division and neuronal morphogenesis. It is hypothesized that the KATNB1-associated MLIS is the result of a combined effect of reduced neural progenitor populations and impaired interaction between the Katanin P80 subunit (encoded by KATNB1) and LIS1 (also known as PAFAH1B1), a protein mutated in type 1 lissencephaly.
|Gene||Location||Protein encoded||OMIM number|
|DMRTA2 (DMRT5)||1p32.3||Doublesex- And Mab-3-Related Transcription Factor 5||614804|
|DYNC1H1||14q32.31||Cytoplasmic Dynein 1 Heavy Chain 1||600112|
|KATNB1||16q21||Katanin p80 subunit B1||602703|
|NDE1||16p13.11||NudE Neurodevelopment Protein 1||609449|
|RNU4ATAC||2q14.2||U4atac small nuclear RNA (snRNA)||601428|
|TUBA1A||12q13.12||Alpha Tubulin 1A||602529|
|TUBA3E||2q21.1||Alpha Tubulin 3E||N/A|
|TUBB2B||6p25.2||Beta Tubulin 2B||612850|
|TUBB3||16q24.3||Beta Tubulin 3||602661|
|TUBG1||17q21.2||Gamma Tubulin 1||191135|
|WDR62||19q13.12||WD Repeat-containing protein 62||613583|
|WDR81||17p13.3||WD Repeat-containing protein 81||614218|
A loss-of-function mutation in the Doublesex- and Mab-3–Related Transcription factor A2 (DMRTA2, also known as DMRT5) gene has been reported in a case of MLIS, implicating DMRTA2 as a critical regulator of cortical neural progenitor cell dynamics.
Another gene that could be involved in the pathogenesis of MLIS is WDR81. Compound heterozygous mutations in WDR81 were found in seven cases from five non-consanguineous families with microcephaly and extremely reduced gyration including agyria (no gyri). WDR81 is suggested to play a role in normal cell proliferation.
Microlissencepahly is considered a tubulinopathy (tubulin gene defect) i.e. it can be caused by mutations in tubulin genes, mainly TUBA1A (Figure 3) and less commonly TUBB2B, TUBB3, TUBA3E, and TUBG1. Central pachygyria (unusually thick convolutions of the cerebral cortex) and polymicrogyria (multiple small gyri) are more commonly seen in patients with defects in TUBB2B, TUBB3, and TUBB5. This implies the critical role of the microtubule cytoskeleton in the pathophysiology of MLIS as well as other neuronal migration disorders.
RNU4ATAC is a gene on chromosome 2 which encodes for a small nuclear RNA (snRNA) called U4atac. U4atac is a part of the U12-dependent minor spliceosome complex. Mutation in this protein is associated with "microcephalic osteodysplastic primordial dwarfism" (MOPD1) which can involve MLIS.
Due to the rarity of the disease, there is still no consensus on the exact clinical picture of MLIS. At birth, lissencephaly with a head circumference of less than minus three standard deviations (< –3 SD) is considered MLIS.
MLIS is a classic finding of holoprosencephaly, where the forebrain of the embryo fails to develop into two cerebral hemispheres. MLIS may arise as a part of Baraitser-Winter syndrome which comprises also ptosis, coloboma, hearing loss and learning disability. Moreover, it is the distinct developmental brain abnormality in "microcephalic osteodysplastic primordial dwarfism" (MOPD1). MLIS may be accompanied by micromelia (shortening of the limbs) as in Basel-Vanagaite-Sirota syndrome (also known as Microlissencephaly-Micromelia syndrome).
|MLIS Type A (Norman–Roberts syndrome or Dobyns-Barkovich type 6†) is an MLIS with thick cortex. Homozygous RELN mutation leads to absence of normal cortical folds, cerebellar hypoplasia, brain stem abnormalities, ocular anomalies, seizures, hypotonia, and severe cognitive delay. This entity could be identical to lissencephaly with cerebellar hypoplasia type B (LCHb).|
|MLIS Type B (Barth microlissencephaly syndrome or Dobyns-Barkovich type 8†) is characterized by severe congenital MLIS with thick cortex, infratentorial anomalies e.g. pontocerebellar hypoplasia and agenesis of corpus callosum. The Barth-type of MLIS is the most severe of all the known lissencephaly syndromes with a high mortality rate. This phenotype consists of polyhydramnios (probably due to poor fetal swallowing), weak respiratory effort.
Barth, after whom the subtype is named, described two siblings with this type as having a very low brain weight, wide ventricles, a very thin neopallium, absent corpus callosum and absent olfactory nerve.
|MLIS with mildly to moderately thick (6–8 mm) cortex with callosal agenesis.|
|Baraitser-Winter syndrome: MLIS with ptosis, coloboma, hearing loss, and learning disability.|
|Seckel syndrome: MLIS with severe, proportional short stature|
|Microcephalic osteodysplastic primordial dwarfism type I (MOPD1)|
|Basel-Vanagaite-Sirota syndrome (Microlissencephaly-Micromelia syndrome): MLIS and micromelia|
†Dobyns and Barkovich classified patients with severe microcephaly and gyral abnormalities (including microcephaly with simplified gyral pattern (MSGP), MLIS and polymicrogyria (multiple small gyri)) into ten groups. MSGP represented the first four groups, MLIS referred to the groups from 5-8 and polymicrogyria in the last two groups.
An algorithm for the diagnosis of all malformations of cortical development is illustrated in Figure 4. MLIS diagnosis can be confirmed by prenatal MRI (Figure 3) which is better than ultrasound in the prenatal detection of MLIS or MSGP. The ideal time for proper prenatal diagnosis is between the 34th and 35th gestational week which is the time when the secondary gyration normally terminates. In MLIS cases, the primary sulci would be unusually wide and flat while secondary sulci would be missing.
MLIS is considered a more severe form than microcephaly with simplified gyral pattern. MLIS is characterized by a smooth cortical surface (absent sulci and gyri) with a thickened cortex (>3 mm) and is usually associated with other congenital anomalies. Microcephaly with a simplified gyral pattern has too few sulci and a normal cortical thickness (3 mm) and is usually an isolated anomaly. A comparison between MLIS and MSGP is summarized in (Table 3).
|Mode of inheritance (if genetic)||Autosomal recessive|
|Cortical thickness||thickened (>3 mm)||normal (3 mm)|
|Cortical surface||smooth (no sulci)||too few sulci|
|Severity||Severe form||Mild form|
|Associated anomalies?||usually present||not present (MSGP is usually isolated)|
The treatment of microlissencephaly and other malformations of cortical development is mostly symptomatic. Developmental delay is managed with neurorehabilitation, including physical and occupational therapy, and speech and feeding therapy. The management of epilepsy in microlissencephalic cases is complicated and depends on the underlying basis of the epileptiform activity. There are two aspects of neuronal functions that could generally contribute to epilepsy, either the epileptic intrinsic properties of neurons or the abnormally epileptic circuits of groups of neurons. In each case, the therapeutic approach differs. If the reason is abnormal epileptogenic circuits, then the neurosurgical resection of such zones would be beneficial. On the other side, if the abnormality arises from abnormal channels or receptors then the pharmacological approach could control epilepsy. However, it is still difficult to make a clear distinction between both mechanisms. Animal model studies are encouraged to further investigate how MLIS mutations in the aforementioned genes can lead to epilepsy which can help improve the understanding and management of epilepsy in those cases.
Genetic counseling of family members is important in all cases of malformation of cortical developments (MCDs) and should include the type of mutation, the mutated genes as well as an explanation of the resultant clinical picture, particularly for subsequent pregnancies. In families with known molecular etiology, prenatal testing in the form of chorionic villus sampling or amniocentesis can be offered to guide subsequent pregnancies. Preimplantation genetic diagnosis (PGD) would be an option as well for those families.
Depending on the underlying pathogenesis, survival in MLIS varies from days to years. It can lead to an early fatal outcome during the neonatal period.
Figure 4 | The cytoplasmic dynein complex and its regulators: the dynactin complex (green) and LIS1/NDE1/NDEL1 (orange-red).
Lissencephaly can result from a mutated LIS1 gene. LIS1 is a protein, normally essential for targeting of cytoplasmic dynein to the plus-end of microtubules. It was demonstrated that LIS1 (PAFAH1B1) is substantially degraded by calpain protein (encoded by CAPN1 and CAPN2) after reaching the plus-end of microtubule. In an animal experiment, a calpain inhibitor called ALLN (Acetyl-Leucyl-Leucyl-Norleucinal) was applied to mice with LIS1 mutation. This has restored LIS1 to normal levels in neurons and consequently, improved neuronal migration and rescued apoptotic neuronal cell death. This provides a proof-of-principle for a potential therapeutic intervention for lissencephaly in the future.
Although LIS1 is not specifically mutated in MLIS, it is a part of a complex involving NDE1 and dynein DYNC1H1 gene, which both can be mutated in MLIS. This LIS1/NDE1/NDEL1/cytoplasmic dynein complex (Figure 4) plays a role in the regulation of neuron proliferation, migration, and intracellular transport. Targeting this complex in utero and throughout development could theoretically and potentially improve the outcome of microlissencephaly. Experimental animal studies are recommended to investigate the effect of calpain inhibitors in microlissencephaly.
MLIS is a rare disease. There is not much information available about the epidemiology of microlissencepahly in the literature. A Ph.D. thesis has estimated the prevalence of microlissencepahly in South-Eastern Hungary between July 1992 and June 2006 to be one case in every 91,000 live births (incidence of 1.1 per 100,000 newborns).
In 1976, the first syndrome with MLIS was reported, now known as Norman–Roberts syndrome (MLIS type A). The Barth type (MLIS type B) was for the first time described in 1982 in two siblings who died soon after birth.
The author declares no conflict of interest.
- Fallet-Bianco, Catherine; Laquerrière, Annie; Poirier, Karine; Razavi, Ferechte; Guimiot, Fabien; Dias, Patricia; Loeuillet, Laurence; Lascelles, Karine et al. (2014-07-25). "Mutations in tubulin genes are frequent causes of various foetal malformations of cortical development including microlissencephaly". Acta Neuropathologica Communications 2: 69. doi:10.1186/2051-5960-2-69. ISSN 2051-5960. https://doi.org/10.1186/2051-5960-2-69.
- Barkovich, A.; Ferriero, Donna; Barr, R.; Gressens, P.; Dobyns, W.; Truwit, Ch.; Evrard, Ph. (June 1998). "Microlissencephaly: A Heterogeneous Malformation of Cortical Development". Neuropediatrics 29 (3): 113–119. doi:10.1055/s-2007-973545. PMID 9706619.
- Pang, Trudy; Atefy, Ramin; Sheen, Volney (2008). "Malformations of Cortical Development". The Neurologist 14 (3): 181–191. doi:10.1097/NRL.0b013e31816606b9. ISSN 1074-7931. PMC 3547618. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3547618/. (primary reference)
- Razek, A. A. K. Abdel; Kandell, A. Y.; Elsorogy, L. G.; Elmongy, A.; Basett, A. A. (2009-01-01). "Disorders of Cortical Formation: MR Imaging Features". American Journal of Neuroradiology 30 (1): 4–11. doi:10.3174/ajnr.A1223. ISSN 0195-6108. PMID 18687750. http://www.ajnr.org/content/30/1/4.
- Cicuto Ferreira Rocha, Nelci Adriana; de Campos, Ana Carolina; Cicuto Ferreira Rocha, Fellipe; Pereira dos Santos Silva, Fernanda (2017-11-01). "Microcephaly and Zika virus: Neuroradiological aspects, clinical findings and a proposed framework for early evaluation of child development". Infant Behavior and Development 49 (Supplement C): 70–82. doi:10.1016/j.infbeh.2017.07.002. http://www.sciencedirect.com/science/article/pii/S0163638316301345.
- Hutton, Chloe; De Vita, Enrico; Ashburner, John; Deichmann, Ralf; Turner, Robert (2008-05-01). "Voxel-based cortical thickness measurements in MRI". NeuroImage 40 (4): 1701–1710. doi:10.1016/j.neuroimage.2008.01.027. ISSN 1053-8119. PMID 18325790. PMC 2330066. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2330066/.
- Gaitanis, John N.; Walsh, Christopher A. (May 2004). "Genetics of disorders of cortical development". Neuroimaging Clinics of North America 14 (2): 219–229, viii. doi:10.1016/j.nic.2004.03.007. ISSN 1052-5149. PMID 15182816.
- Verloes, Alain; Drunat, Séverine; Gressens, Pierre; Passemard, Sandrine (1993), Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E. (eds.), "Primary Autosomal Recessive Microcephalies and Seckel Syndrome Spectrum Disorders", GeneReviews®, University of Washington, Seattle, PMID 20301772, retrieved 2018-11-06
- Abdel-Salam, Ghada M.H.; Abdel-Hamid, Mohamed S.; Saleem, Sahar N.; Ahmed, Mahmoud K.H.; Issa, Mahmoud; Effat, Laila K.; Kayed, Hisham F.; Zaki, Maha S. et al. (2012-08-01). "Profound microcephaly, primordial dwarfism with developmental brain malformations: A new syndrome". American Journal of Medical Genetics Part A 158A (8): 1823–1831. doi:10.1002/ajmg.a.35480. ISSN 1552-4833. http://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.35480/abstract.
- Cavallin, Mara; Rujano, Maria A.; Bednarek, Nathalie; Medina-Cano, Daniel; Bernabe Gelot, Antoinette; Drunat, Severine; Maillard, Camille; Garfa-Traore, Meriem et al. (2017-10-01). "WDR81 mutations cause extreme microcephaly and impair mitotic progression in human fibroblasts and Drosophila neural stem cells". Brain: A Journal of Neurology 140 (10): 2597–2609. doi:10.1093/brain/awx218. ISSN 1460-2156. PMID 28969387.
- Szklarczyk, Damian; Franceschini, Andrea; Wyder, Stefan; Forslund, Kristoffer; Heller, Davide; Huerta-Cepas, Jaime; Simonovic, Milan; Roth, Alexander et al. (January 2015). "STRING v10: protein-protein interaction networks, integrated over the tree of life". Nucleic Acids Research 43 (Database issue): D447–452. doi:10.1093/nar/gku1003. ISSN 1362-4962. PMID 25352553. PMC 4383874. https://www.ncbi.nlm.nih.gov/pubmed/25352553.
- Harding, Brian N.; Moccia, Amanda; Drunat, Séverine; Soukarieh, Omar; Tubeuf, Hélène; Chitty, Lyn S.; Verloes, Alain; Gressens, Pierre et al. (2016-08-04). "Mutations in Citron Kinase Cause Recessive Microlissencephaly with Multinucleated Neurons". The American Journal of Human Genetics 99 (2): 511–520. doi:10.1016/j.ajhg.2016.07.003. ISSN 0002-9297. PMID 27453579. http://www.cell.com/ajhg/abstract/S0002-9297(16)30275-0.
- Verloes, A.; Elmaleh, M.; Gonzales, M.; Laquerrière, A.; Gressens, P. (2007-05-01). "Lissencéphalies : aspects cliniques et génétiques". Revue Neurologique 163 (5): 533–547. doi:10.1016/S0035-3787(07)90460-9. http://www.sciencedirect.com/science/article/pii/S0035378707904609.
- Houlihan, Shauna L; Feng, Yuanyi (2014-09-23). "The scaffold protein Nde1 safeguards the brain genome during S phase of early neural progenitor differentiation". eLife 3. doi:10.7554/eLife.03297. ISSN 2050-084X. https://elifesciences.org/articles/03297.
- Bakircioglu, Mehmet; Carvalho, Ofélia P.; Khurshid, Maryam; Cox, James J.; Tuysuz, Beyhan; Barak, Tanyeri; Yilmaz, Saliha; Caglayan, Okay et al. (2011-05-13). "The Essential Role of Centrosomal NDE1 in Human Cerebral Cortex Neurogenesis". American Journal of Human Genetics 88 (5): 523–535. doi:10.1016/j.ajhg.2011.03.019. ISSN 0002-9297. PMID 21529752. PMC 3146716. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3146716/.
- Liu, Joan Y. W.; Kasperavičiūtė, Dalia; Martinian, Lillian; Thom, Maria; Sisodiya, Sanjay M. (2012-04-16). "Neuropathology of 16p13.11 Deletion in Epilepsy". PLOS ONE 7 (4): e34813. doi:10.1371/journal.pone.0034813. ISSN 1932-6203. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0034813.
- Mishra-Gorur, Ketu; Çağlayan, Ahmet Okay; Schaffer, Ashleigh E.; Chabu, Chiswili; Henegariu, Octavian; Vonhoff, Fernando; Akgümüş, Gözde Tuğce; Nishimura, Sayoko et al. (2014-12-17). "Mutations in KATNB1 Cause Complex Cerebral Malformations by Disrupting Asymmetrically Dividing Neural Progenitors". Neuron 84 (6): 1226–1239. doi:10.1016/j.neuron.2014.12.014. ISSN 0896-6273. https://www.sciencedirect.com/science/article/pii/S0896627314010952.
- Yigit, Gökhan; Wieczorek, Dagmar; Bögershausen, Nina; Beleggia, Filippo; Möller-Hartmann, Claudia; Altmüller, Janine; Thiele, Holger; Nürnberg, Peter et al. (2016-03-01). "A syndrome of microcephaly, short stature, polysyndactyly, and dental anomalies caused by a homozygous KATNB1 mutation". American Journal of Medical Genetics Part A 170 (3): 728–733. doi:10.1002/ajmg.a.37484. ISSN 1552-4833. http://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.37484/abstract.
- Poirier, Karine; Martinovic, Jelena; Laquerrière, Annie; Cavallin, Mara; Fallet-Bianco, Catherine; Desguerre, Isabelle; Valence, Stephanie; Grande-Goburghun, Jocelyne et al. (2015-08-01). "Rare ACTG1 variants in fetal microlissencephaly". European Journal of Medical Genetics 58 (8): 416–418. doi:10.1016/j.ejmg.2015.06.006. http://www.sciencedirect.com/science/article/pii/S1769721215001147.
- Young, Fraser I.; Keruzore, Marc; Nan, Xinsheng; Gennet, Nicole; Bellefroid, Eric J.; Li, Meng (2017-07-11). "The doublesex-related Dmrta2 safeguards neural progenitor maintenance involving transcriptional regulation of Hes1". Proceedings of the National Academy of Sciences 114 (28): E5599–E5607. doi:10.1073/pnas.1705186114. ISSN 0027-8424. PMID 28655839. http://www.pnas.org/content/114/28/E5599.
- Zillhardt, Julia Lauer; Poirier, Karine; Broix, Loïc; Lebrun, Nicolas; Elmorjani, Adrienne; Martinovic, Jelena; Saillour, Yoann; Muraca, Giuseppe et al. (April 2016). "Mosaic parental germline mutations causing recurrent forms of malformations of cortical development". European journal of human genetics: EJHG 24 (4): 611–614. doi:10.1038/ejhg.2015.192. ISSN 1476-5438. PMID 26395554. PMC PMC4929884. https://www.ncbi.nlm.nih.gov/pubmed/26395554.
- Bahi-Buisson, Nadia; Cavallin, Mara (1993), Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E. (eds.), "Tubulinopathies Overview", GeneReviews®, University of Washington, Seattle, PMID 27010057, retrieved 2018-11-06
- Chang, Bernard S. (2015). "Tubulinopathies and Their Brain Malformation Syndromes: Every TUB on Its Own Bottom". Epilepsy Currents 15 (2): 65–67. doi:10.5698/1535-7597-15.2.65. ISSN 1535-7597. PMID 26251641. PMC 4519017. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4519017/.
- Chakraborti, Soumyananda; Natarajan, Kathiresan; Curiel, Julian; Janke, Carsten; Liu, Judy (October 2016). "The emerging role of the tubulin code: From the tubulin molecule to neuronal function and disease". Cytoskeleton 73 (10): 521–550. doi:10.1002/cm.21290. ISSN 1949-3592. PMID 26934450.
- Sweet, Kevin M.; Shaw, Dennis W. W.; Chapman, Teresa (2017-06-01). "Cerebral palsy and seizures in a child with tubulinopathy pattern dysgenesis and focal cortical dysplasia". Radiology Case Reports 12 (2): 396–400. doi:10.1016/j.radcr.2016.12.008. http://www.sciencedirect.com/science/article/pii/S1930043316302485.
- Krøigård, Anne Bruun; Frost, Morten; Larsen, Martin Jakob; Ousager, Lilian Bomme; Frederiksen, Anja Lisbeth (2016). "Bone structure in two adult subjects with impaired minor spliceosome function resulting from RNU4ATAC mutations causing microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1)". Bone 92: 145–149. doi:10.1016/j.bone.2016.08.023. ISSN 8756-3282. https://www.sciencedirect.com/science/article/pii/S8756328216302435.
- Bamba, Yohei; Shofuda, Tomoko; Kato, Mitsuhiro; Poo h, Ritsuko K.; Tateishi, Yoko; Takanashi, Jun-ichi; Utsunomiya, Hidetsuna; Sumida, Miho et al. (2016-07-19). "In vitro characterization of neurite extension using induced pluripotent stem cells derived from lissencephaly patients with TUBA1A missense mutations". Molecular Brain 9: 70. doi:10.1186/s13041-016-0246-y. ISSN 1756-6606. https://doi.org/10.1186/s13041-016-0246-y.
- Kato, Mitsuhiro (2015-05-21). "Genotype-phenotype correlation in neuronal migration disorders and cortical dysplasias". Frontiers in Neuroscience 9. doi:10.3389/fnins.2015.00181. ISSN 1662-4548. PMID 26052266. PMC 4439546. //www.ncbi.nlm.nih.gov/pmc/articles/PMC4439546/.
- Sarici, Dilek; Akin, Mustafa Ali; Kara, Ahu; Doganay, Selim; Kurtoglu, Selim (March 2012). "Seckel syndrome accompanied by semilobar holoprosencephaly and arthrogryposis". Pediatric Neurology 46 (3): 189–191. doi:10.1016/j.pediatrneurol.2012.01.002. ISSN 1873-5150. PMID 22353298. https://www.ncbi.nlm.nih.gov/pubmed/22353298.
- Klinge, L.; Schaper, J.; Wieczorek, D.; Voit, T. (2002). "Microlissencephaly in Microcephalic Osteodysplastic Primordial Dwarfism: A Case Report and Review of the Literature". Neuropediatrics 33 (06): 309–313. doi:10.1055/s-2002-37086. ISSN 0174-304X. https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-2002-37086.
- Kumar, Suresh; Suthar, Renu; Panigrahi, Inusha; Marwaha, Ram Kumar (2013-11-01). "Lissencephaly presenting with congenital hypothyroidism". Journal of Pediatric Endocrinology and Metabolism 26 (11-12). doi:10.1515/jpem-2013-0102. ISSN 2191-0251. https://www.degruyter.com/view/j/jpem.2013.26.issue-11-12/jpem-2013-0102/jpem-2013-0102.xml.
- Scala, Iris; Titomanlio, Luigi; Del Giudice, Ennio; Passemard, Sandrine; Figliuolo, Chiara; Annunziata, Patrizia; Granese, Barbara; Scarpato, Elena et al. (November 2010). "Absence of microcephalin gene mutations in a large cohort of non-consanguineous patients with autosomal recessive primary microcephaly". American Journal of Medical Genetics. Part A 152A (11): 2882–2885. doi:10.1002/ajmg.a.33672. ISSN 1552-4833. PMID 20949544. https://www.ncbi.nlm.nih.gov/pubmed/20949544.
- Barkovich, A. J.; Kuzniecky, R. I.; Jackson, G. D.; Guerrini, R.; Dobyns, W. B. (2005-12-27). "A developmental and genetic classification for malformations of cortical development" (in en). Neurology 65 (12): 1873–1887. doi:10.1212/01.wnl.0000183747.05269.2d. ISSN 0028-3878. PMID 16192428. http://n.neurology.org/content/65/12/1873.
- Katz, Olivia L.; Krantz, Ian D.; Noon, Sarah E. (2016-04-20). "Interstitial deletion of 7q22.1q31.1 in a boy with structural brain abnormality, cardiac defect, developmental delay, and dysmorphic features" (in en). American Journal of Medical Genetics Part C: Seminars in Medical Genetics 172 (2): 92–101. doi:10.1002/ajmg.c.31485. ISSN 1552-4868. https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.c.31485.
- Doherty, Dan; Poretti, Andrea (2017), "Disorders of Cerebellar and Brainstem Development", Swaiman's Pediatric Neurology, Elsevier, pp. 199–207, doi:10.1016/b978-0-323-37101-8.00027-8, ISBN 9780323371018, retrieved 2018-11-06
- Mirzaa, Ghayda M.; Dobyns, William B. (2017), "Disorders of Brain Size", Swaiman's Pediatric Neurology, Elsevier, pp. 208–217, doi:10.1016/b978-0-323-37101-8.00028-x, ISBN 9780323371018, retrieved 2018-11-06
- Dobyns, William B.; Leventer, Richard J.; Guerrini, Renzo (2017), "Malformations of Cortical Development", Swaiman's Pediatric Neurology, Elsevier, pp. 218–225, doi:10.1016/b978-0-323-37101-8.00029-1, ISBN 9780323371018, retrieved 2018-11-06
- Kroon, A.; Smit, B.; Barth, P.; Hennekam, R. (October 1996). "Lissencephaly with Extreme Cerebral and Cerebellar Hypoplasia. A Magnetic Resonance Imaging Study". Neuropediatrics 27 (05): 273–276. doi:10.1055/s-2007-973778. ISSN 0174-304X. https://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-973778.
- Dobyns, W.; Barkovich, A. (1999). "Microcephaly with Simplified Gyral Pattern (Oligogyric Microcephaly) and Microlissencephaly". Neuropediatrics 30 (02): 104–106. doi:10.1055/s-2007-973471. ISSN 0174-304X. https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-2007-973471.
- Sztriha, L.; Dawodu, A.; Gururaj, A.; Johansen, J. G. (2004). "Microcephaly Associated with Abnormal Gyral Pattern". Neuropediatrics 35 (6): 346–352. doi:10.1055/s-2004-830430. ISSN 0174-304X. https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-2004-830430.
- Lee, Jeehun (2017). "Malformations of cortical development: genetic mechanisms and diagnostic approach". Korean Journal of Pediatrics 60 (1): 1. doi:10.3345/kjp.2017.60.1.1. ISSN 1738-1061. PMID 28203254. PMC PMC5309318. https://kjp.or.kr/journal/view.php?doi=10.3345/kjp.2017.60.1.1.
- Salomon, L. J.; Garel, C. (December 2007). "Magnetic resonance imaging examination of the fetal brain". Ultrasound in Obstetrics & Gynecology: The Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology 30 (7): 1019–1032. doi:10.1002/uog.5176. ISSN 0960-7692. PMID 17994613.
- Gembruch, Ulrich; Hecher, Kurt; Steiner, Horst, eds. (2013). Ultraschalldiagnostik in Geburtshilfe und Gynäkologie (in German). doi:10.1007/978-3-642-29633-8.
- Jamuar, Saumya S.; Walsh, Christopher A. (06-2015). "Genomic Variants and Variations in Malformations of Cortical Development". Pediatric clinics of North America 62 (3): 571–585. doi:10.1016/j.pcl.2015.03.002. ISSN 0031-3955. PMID 26022163. PMC PMC4449454. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449454/.
- Saito, Yoshiaki; Sugai, Kenji; Nakagawa, Eiji; Sakuma, Hiroshi; Komaki, Hirofumi; Sasaki, Masayuki; Maegaki, Yoshihiro; Ohno, Kousaku et al. (2009-02-15). "Treatment of epilepsy in severely disabled children with bilateral brain malformations". Journal of the Neurological Sciences 277 (1-2): 37–49. doi:10.1016/j.jns.2008.10.009. ISSN 0022-510X. https://www.sciencedirect.com/science/article/pii/S0022510X0800511X.
- Schwartzkroin, P. A.; Walsh, C. A. (2000). "Cortical malformations and epilepsy". Mental Retardation and Developmental Disabilities Research Reviews 6 (4): 268–280. doi:10.1002/1098-2779(2000)6:43.0.CO;2-B. ISSN 1080-4013. PMID 11107192. https://www.ncbi.nlm.nih.gov/pubmed/11107192.
- Jaarsma, Dick; Hoogenraad, Casper C. (2015). "Cytoplasmic dynein and its regulatory proteins in Golgi pathology in nervous system disorders". Frontiers in Neuroscience 9. doi:10.3389/fnins.2015.00397. ISSN 1662-453X. https://www.frontiersin.org/articles/10.3389/fnins.2015.00397/full.
- Yamada, Masami; Yoshida, Yuko; Mori, Daisuke; Takitoh, Takako; Kengaku, Mineko; Umeshima, Hiroki; Takao, Keizo; Miyakawa, Tsuyoshi et al. (2009-10). "Inhibition of calpain increases LIS1(PAFAH1B1) and partially rescues in vivo phenotypes in a mouse model of lissencephaly". Nature medicine 15 (10): 1202–1207. doi:10.1038/nm.2023. ISSN 1078-8956. PMID 19734909. PMC PMC2759411. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759411/.
- Gilbert, James; Man, Heng-Ye (2017). "Fundamental Elements in Autism: From Neurogenesis and Neurite Growth to Synaptic Plasticity". Frontiers in Cellular Neuroscience 11. doi:10.3389/fncel.2017.00359. ISSN 1662-5102. https://www.frontiersin.org/articles/10.3389/fncel.2017.00359/full.
- Szabó, Nóra Zsuszanna (2012-05-14). Epidemiology of central nervous system malformations in South-Eastern Hungary (Thesis) (in Hungarian). University of Szeged. doi:10.14232/phd.1485.
- Norman, M. G.; Roberts, M.; Sirois, J.; Tremblay, L. J. (February 1976). "Lissencephaly". The Canadian Journal of Neurological Sciences 3 (1): 39–46. doi:10.1017/S0317167100025981. ISSN 0317-1671. PMID 175907.