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Lissencephaly 10(LIS10)

MedGen UID:
1719546
Concept ID:
C5394354
Disease or Syndrome
Synonyms: LIS10; LISSENCEPHALY 10
 
Gene (location): CEP85L (6q22.31)
 
Monarch Initiative: MONDO:0030031
OMIM®: 618873

Definition

Lissencephaly-10 (LIS10) is a neurologic disorder characterized by variably delayed development with mildly to moderately impaired intellectual development and language delay, as well as seizures, which are often intractable. There is a spectrum of severity, with some patients having normal early development and only borderline to mild cognitive impairment. Brain imaging shows features consistent with neuronal migration defects, including posterior-predominant lissencephaly, pachygyria, agyria, and subcortical band heterotopia (summary by Tsai et al., 2020). For a general description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432). [from OMIM]

Clinical features

From HPO
Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Individual Behavior
Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).
Bipolar affective disorder
MedGen UID:
2649
Concept ID:
C0005586
Mental or Behavioral Dysfunction
Bipolar disorder is an illness of mood characterized by alternating episodes of elevated and depressed moods, which are interspersed with euthymic periods.
Febrile seizure (within the age range of 3 months to 6 years)
MedGen UID:
3232
Concept ID:
C0009952
Disease or Syndrome
A febrile seizure is any type of seizure (most often a generalized tonic-clonic seizure) occurring with fever (at least 38 degrees Celsius) but in the absence of central nervous system infection, severe metabolic disturbance or other alternative precipitant in children between the ages of 3 months and 6 years.
Depression
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.
Torticollis
MedGen UID:
11859
Concept ID:
C0040485
Sign or Symptom
Torticollis is a twisted neck as a result of shortening of sternocleidomastoid muscle. This short and fibrotic muscle pulls the head laterally and rotates the chin and face to the opposite end. Facial asymmetry may be a manifestation (summary by Engin et al., 1997).
EEG abnormality
MedGen UID:
56235
Concept ID:
C0151611
Finding
Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp.
Auditory hallucination
MedGen UID:
115932
Concept ID:
C0233762
Sign or Symptom
Perception of sounds without auditory stimulus.
Visual agnosia
MedGen UID:
115959
Concept ID:
C0234502
Finding
The condition is known as visual agnosia, which refers to the inability to recognize objects that are visually presented, even though the individual may have normal visual field, acuity, color vision, brightness discrimination, language, and memory.
Generalized-onset seizure
MedGen UID:
115963
Concept ID:
C0234533
Disease or Syndrome
A generalized-onset seizure is a type of seizure originating at some point within, and rapidly engaging, bilaterally distributed networks. The networks may include cortical and subcortical structures but not necessarily the entire cortex.
Macrogyria
MedGen UID:
120579
Concept ID:
C0266483
Congenital Abnormality
Pachygyria is a malformation of cortical development with abnormally wide gyri with sulci 1,5-3 cm apart and abnormally thick cortex measuring more than 5 mm (radiological definition). See also neuropathological definitions for 2-, 3-, and 4-layered lissencephaly.
Focal impaired awareness seizure
MedGen UID:
543022
Concept ID:
C0270834
Disease or Syndrome
Focal impaired awareness seizure (or focal seizure with impaired or lost awareness) is a type of focal-onset seizure characterized by some degree (which may be partial) of impairment of the person's awareness of themselves or their surroundings at any point during the seizure.
Tonic seizure
MedGen UID:
82855
Concept ID:
C0270844
Disease or Syndrome
A tonic seizure is a type of motor seizure characterized by unilateral or bilateral limb stiffening or elevation, often with neck stiffening.
Atonic seizure
MedGen UID:
78735
Concept ID:
C0270846
Disease or Syndrome
Atonic seizure is a type of motor seizure characterized by a sudden loss or diminution of muscle tone without apparent preceding myoclonic or tonic event lasting about 1 to 2 seconds, involving head, trunk, jaw, or limb musculature.
Suicidal ideation
MedGen UID:
140856
Concept ID:
C0424000
Finding
Frequent thoughts about or preoccupation with killing oneself.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Atypical absence seizure
MedGen UID:
108888
Concept ID:
C0595948
Disease or Syndrome
An atypical absence seizure is a type of generalized non-motor (absence) seizure characterized by interruption of ongoing activities and reduced responsiveness. In comparison to a typical absence seizure, changes in tone may be more pronounced, onset and/or cessation may be less abrupt, and the duration of the ictus and post-ictal recovery may be longer. Although not always available, an EEG often demonstrates slow (<3 Hz), irregular, generalized spike-wave activity.
Autistic behavior
MedGen UID:
163547
Concept ID:
C0856975
Mental or Behavioral Dysfunction
Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.
Bilateral tonic-clonic seizure with focal onset
MedGen UID:
164077
Concept ID:
C0877017
Disease or Syndrome
A bilateral tonic-clonic seizure with focal onset is a focal-onset seizure which progresses into a bilateral tonic-clonic phase.
Agyria
MedGen UID:
361827
Concept ID:
C1879312
Congenital Abnormality
A congenital abnormality of the cerebral hemisphere characterized by lack of gyrations (convolutions) of the cerebral cortex. Agyria is defined as cortical regions lacking gyration with sulci great than 3 cm apart and cerebral cortex thicker than 5 mm.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Generalized non-motor (absence) seizure
MedGen UID:
1385688
Concept ID:
C4316903
Disease or Syndrome
A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterized by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features.
Myoclonic seizure
MedGen UID:
1385980
Concept ID:
C4317123
Sign or Symptom
A myoclonic seizure is a type of motor seizure characterized by sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus.
Posterior predominant subcortical band heterotopia
MedGen UID:
1691332
Concept ID:
C5139325
Disease or Syndrome
Longitudinal bands of gray matter located deep to the cerebral cortex and separated from it by a thin layer of normal appearing white matter visible along the occipital cortex.
Mild microcephaly
MedGen UID:
332294
Concept ID:
C1836806
Congenital Abnormality
Decreased occipito-frontal (head) circumference (OFC). For the microcephaly OFC must be between -3 SD and -2 SD compared to appropriate, age matched, normal standards (i.e. -3 SD <= OFC < -2 SD).
Partial congenital absence of teeth
MedGen UID:
43794
Concept ID:
C0020608
Congenital Abnormality
Tooth agenesis in some form is a common human anomaly that affects approximately 20% of the population. Although tooth agenesis is associated with numerous syndromes, several case reports describe nonsyndromic forms that are either sporadic or familial in nature, as reviewed by Gorlin et al. (1990). The incidence of familial tooth agenesis varies with each class of teeth. Most commonly affected are third molars (wisdom teeth), followed by either upper lateral incisors or lower second premolars; agenesis involving first and second molars is very rare. Also see 114600 and 302400. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). Faulty use of the terms, however, have confounded their use. The term 'partial anodontia' is obsolete (Salinas, 1978). Genetic Heterogeneity of Selective Tooth Agenesis Other forms of selective tooth agenesis include STHAG2 (602639), mapped to chromosome 16q12; STHAG3 (604625), caused by mutation in the PAX9 gene (167416) on chromosome 14q12; STHAG4 (150400), caused by mutation in the WNT10A gene (606268) on chromosome 2q35; STHAG5 (610926), mapped to chromosome 10q11; STHAG7 (616724), caused by mutation in the LRP6 gene (603507) on chromosome 12p13; STHAG8 (617073), caused by mutation in the WNT10B gene (601906) on chromosome 12q13; STHAG9 (617275), caused by mutation in the GREM2 gene (608832) on chromosome 1q43; STHAG10 (620173), caused by mutation in the TSPEAR gene (612920) on chromosome 21q22; and STHAGX1 (313500), caused by mutation in the EDA gene (300451) on chromosome Xq13. A type of selective tooth agenesis that was formerly designated STHAG6 has been incorporated into the dental anomalies and short stature syndrome (DASS; 601216). Of 34 unrelated patients with nonsyndromic tooth agenesis, van den Boogaard et al. (2012) found that 56% (19 patients) had mutations in the WNT10A gene (STHAG4), whereas only 3% and 9% had mutations in the MSX1 (STHAG1) and PAX9 (STHAG3) genes, respectively. The authors concluded that WNT10A is a major gene in the etiology of isolated hypodontia. Genotype-Phenotype Correlations Yu et al. (2016) observed that the most frequently missing permanent teeth in WNT10B-associated oligodontia were the lateral incisors (83.3%), whereas premolars were missing only 51.4% of the time, which they noted was a pattern 'clearly different' from the oligodontia patterns resulting from WNT10A mutations. They also stated that the selective pattern in WNT10B mutants was different from that associated with mutations in other genes, such as MSX1, in which second premolars are missing, and PAX9, in which there is agenesis of molars.
Cerebral visual impairment
MedGen UID:
890568
Concept ID:
C4048268
Pathologic Function
A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye.

Professional guidelines

PubMed

Lerman-Sagie T, Pogledic I, Leibovitz Z, Malinger G
Eur J Paediatr Neurol 2021 Sep;34:50-61. Epub 2021 Aug 3 doi: 10.1016/j.ejpn.2021.08.001. PMID: 34390998
Saito K
Prenat Diagn 2006 May;26(5):415-7. doi: 10.1002/pd.1426. PMID: 16570239
Guerrini R, Carrozzo R
Seizure 2001 Oct;10(7):532-43; quiz 544-7. doi: 10.1053/seiz.2001.0650. PMID: 11749114

Recent clinical studies

Etiology

Contrò G, Micalizzi A, Giangiobbe S, Caraffi SG, Zuntini R, Rosato S, Pollazzon M, Terracciano A, Napoli M, Rizzi S, Salerno GG, Radio FC, Niceta M, Parrini E, Fusco C, Gargano G, Guerrini R, Tartaglia M, Novelli A, Zuffardi O, Garavelli L
Genes (Basel) 2021 Aug 5;12(8) doi: 10.3390/genes12081208. PMID: 34440382Free PMC Article

Diagnosis

Contrò G, Micalizzi A, Giangiobbe S, Caraffi SG, Zuntini R, Rosato S, Pollazzon M, Terracciano A, Napoli M, Rizzi S, Salerno GG, Radio FC, Niceta M, Parrini E, Fusco C, Gargano G, Guerrini R, Tartaglia M, Novelli A, Zuffardi O, Garavelli L
Genes (Basel) 2021 Aug 5;12(8) doi: 10.3390/genes12081208. PMID: 34440382Free PMC Article

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