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Lissencephaly


Presentation

  • This case is presented for its rarity and for the documentation of the tissue localization of CMV inclusions at autopsy.[ncbi.nlm.nih.gov]
  • A neonatal case of provisional neurocutaneous melanosis presenting with lissencephaly is reported. Several congenital nevi were observed on the trunk and extremities of the infant, including a giant congenital hairy nevus over the skull.[ncbi.nlm.nih.gov]
  • In the variants of classical lissencephaly, extra-cortical anomalies are also present (total or subtotal agenesis of the corpus callosum and/or cerebellar hypoplasia).[orpha.net]
  • Rare diseases Search Search for a rare disease Microlissencephaly Disease definition Microlissencephaly describes a heterogenous group of a rare cortical malformations characterized by lissencephaly in combination with severe congenital microcephaly, presenting[orpha.net]
  • Patients present with lissencephaly, agenesis of the corpus callosum, refractory epilepsy of neonatal onset, acquired microcephaly and male genotype with ambiguous genitalia.[ncbi.nlm.nih.gov]
Poor Feeding
  • Treatment of manifestations: Poor feeding may require nasogastric tube feedings in newborns and later placement of a gastrostomy tube.[ncbi.nlm.nih.gov]
Collapse
  • CRADD/caspase-2 signaling is implicated in neurotrophic factor withdrawal- and amyloid-β-induced dendritic spine collapse and neuronal apoptosis, suggesting a role in cortical sculpting and plasticity.[ncbi.nlm.nih.gov]
Failure to Thrive
  • Symptoms of the disorder may include unusual facial appearance, difficulty swallowing, failure to thrive, muscle spasms, seizures, and severe psychomotor retardation. Hands, fingers, or toes may be deformed.[ninds.nih.gov]
  • Possible symptoms of lissencephaly include: Failure to thrive: Failure to thrive is a condition often seen in newborns in which growth is not occurring as expected. It can have many causes.[rarediseases.about.com]
Muscle Spasticity
  • Children who are born with lissencephaly suffer from severe motor impairment, seizures, muscle spasticity, muscle hypotonia, facial abnormalities, difficulty swallowing, abnormalities of the limbs, fingers and toes and failure to thrive.[disabilitybenefitscenter.org]
  • They usually present with seizures, muscle spasticity, low muscle tone and a number of other neurological symptoms.[disability-benefits-help.org]
  • Lissencephaly Symptoms Children affected by this disorder may display various symptoms like: Ataxia Seizures Microcephaly Failure to thrive Difficulty in swallowing Unusual facial appearance Hypotonia or muscle spasticity Severe psychomotor retardation[hxbenefit.com]
Muscle Hypotonia
  • Children who are born with lissencephaly suffer from severe motor impairment, seizures, muscle spasticity, muscle hypotonia, facial abnormalities, difficulty swallowing, abnormalities of the limbs, fingers and toes and failure to thrive.[disabilitybenefitscenter.org]
Dolichocephaly
  • D'Annunzio', Medical School, University of Chieti, Chieti, Italy. ccelen@tin.it Abstract We report on an 1-day-old boy with classical lissencephaly (grade 1, according to Kato and Dobyns, 2003) associated with an extended phenotype, including dolichocephaly[ncbi.nlm.nih.gov]
Facial Edema
  • The fetus had normal 46, XY karyotype and similar anomalies found in the index case, with cranio-facial edema and arthrogryposis. X-ray films showed epiphyseal stippling of cervical vertebrae, feet and sacrum.[ncbi.nlm.nih.gov]
Psychomotor Retardation
  • Symptoms of the disorder may include unusual facial appearance, difficulty swallowing, failure to thrive, muscle spasms, seizures, and severe psychomotor retardation. Hands, fingers, or toes may be deformed.[ninds.nih.gov]
  • MR imaging of a patient with epilepsy and psychomotor retardation at 5 months revealed parieto-occipital pachygyria with almost normal cortical appearance and thickness in the frontal region; this appearance evolved into diffuse pachygyria at 7 years.[ncbi.nlm.nih.gov]
  • Clinical description Children with lissencephaly have feeding and swallowing problems, muscle tone anomalies (early hypotonia and subsequently limb hypertonia), seizures (in particular, infantile spasms) and severe psychomotor retardation.[orpha.net]
  • Other symptoms associated to lissencephaly and the disorders associated to it (ILS, Miller-Dieker, Walker-Warburg) include: seizures and spasms, trouble swallowing and feeding, intellectual impairment, malformation in hands and feet and psychomotor retardation[amplexa.com]
Neonate-Onset
  • Patients present with lissencephaly, agenesis of the corpus callosum, refractory epilepsy of neonatal onset, acquired microcephaly and male genotype with ambiguous genitalia.[ncbi.nlm.nih.gov]
  • XLAG is characterized by congenital or postnatal microcephaly, neonatal-onset intractable epilepsy, poor temperature regulation, chronic diarrhea, and abnormal genitalia [ Kato & Dobyns 2003, Kato et al 2004 ].[ncbi.nlm.nih.gov]
Polyuria
  • […] differential diagnoses in this situation are the syndrome of inappropriate antidiuretic hormone secretion, marked by inappropriate retention of free water, and cerebral salt wasting, characterized by excessive urinary loss of sodium and resulting in polyuria[ncbi.nlm.nih.gov]
Seizure
  • Seizures may be particularly problematic but anticonvulsant medications can help.[ninds.nih.gov]
  • […] muscle jerks (myoclonic seizures); and episodes of muscle rigidity, convulsions, and loss of consciousness (tonic-clonic seizures).[ghr.nlm.nih.gov]
  • It is to consider lissencephaly in the diagnosis of developmental delay with seizure disorder as many patients may be diagnosed as cerebral palsy.[ncbi.nlm.nih.gov]
  • Later in infancy the epileptogentic phenotype became more variable and included different forms of focal seizures as well generalized as tonic-clonic seizures, with generalized tonic-clonic seizures being the predominant type.[ncbi.nlm.nih.gov]
  • EEG showed disorganized background activity and seizures starting at the right midtemporal, central and occipital regions.[ncbi.nlm.nih.gov]
Drop Attacks
  • 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[ghr.nlm.nih.gov]

Workup

Hypsarrhythmia
  • Approximately 80% have infantile spasms, although the EEG does not always show the typical hypsarrhythmia pattern. The onset of infantile spasms may be associated with a decline in function.[ncbi.nlm.nih.gov]
Hyponatremia
  • Hyponatremia is the most frequent electrolyte disorder in critically ill neurological patients.[ncbi.nlm.nih.gov]

Treatment

  • Management and treatment Management is symptomatic only (swallowing problems require adapted feeding to prevent food aspiration, articular and respiratory physiotherapy to prevent orthopaedic problems resulting from hyptonia, and treatment of gastrooesophageal[orpha.net]
  • Treatment There is no cure for lissencephaly, but children can show progress in their development over time. Supportive care may be needed to help with comfort, feeding, and nursing needs.[ninds.nih.gov]
  • Thus, SNJ1945 is a potential drug for the treatment of human lissencephaly patients.[ncbi.nlm.nih.gov]
  • The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.[orpha.net]

Prognosis

  • Prognosis The prognosis for children with lissencephaly depends on the degree of brain malformation. Many will die before the age of 10 years. The cause of death is usually aspiration of food or fluids, respiratory disease, or severe seizures.[ninds.nih.gov]
  • After receiving genetic counseling, the parents elected to terminate the pregnancies based on the neuroradiological findings and the associated severe prognosis.[ncbi.nlm.nih.gov]
  • As the disease is associated with poor perinatal prognosis, early and accurate prenatal diagnosis is important for genetic counseling and antenatal care. Thieme Publicações Ltda Rio de Janeiro, Brazil.[ncbi.nlm.nih.gov]
  • The prognosis is often poor, but prenatal diagnosis allows appropriate counseling and optimization of obstetric management.[ncbi.nlm.nih.gov]

Etiology

  • LISI and DCX) has allowed etiologic diagnosis of this disorder feasible.[ncbi.nlm.nih.gov]
  • However, the exact etiology of lissencephaly in humans remains unknown. Research on congenital diseases is limited by the shortage of clinically derived resources, especially for rare pediatric diseases.[ncbi.nlm.nih.gov]
  • Etiology The condition is caused by doublecortin ( DCX, located at Xq22.3-q23) gene mutations.[orpha.net]
  • Among the viral infections, CMV is a very important etiological factor in the causation of lissencephaly. Other causes of central nervous system infections are toxoplasmosis, rubella, herpes simplex, human immunodeficiency virus and syphilis.[doi.org]

Epidemiology

  • Summary Epidemiology The incidence of all forms of type I lissencephaly is around 1 in 100,000 births.[orpha.net]
  • Epidemiology of lissencephaly type I. Neuroepidemiology 1991;10:200-4. 3. Malinger G, Lev D, Zahalka N, Ben Aroia Z, Watemberg N, Kidron D, et al. Fetal cytomegalovirus infection of the brain: The spectrum of sonographic findings.[doi.org]
  • Summary Epidemiology The prevalence is unknown. Clinical description Boys presenting with lissencephaly show an abnormally thick cortex with very few gyri (pachygyria) or even none (agyria).[orpha.net]
Sex distribution
Age distribution

Pathophysiology

  • Using routine immunohistochemistry and confocal microscopy, we show evidence for defects in axonal transport in addition to defects in neuronal migration and differentiation, giving new insights to the pathophysiology of this form of lissencephaly.[ncbi.nlm.nih.gov]
  • In vitro experiments and mutant animal studies, along with neuropathological abnormalities in humans are of invaluable interest for the understanding of pathophysiological mechanisms, highlighting the central role of cytoskeletal dynamics required for[ncbi.nlm.nih.gov]
  • This study emphasizes the importance of neuropathological examinations in cases of lissencephaly for improving our knowledge of the distinct pathogenetic and pathophysiological mechanisms.[ncbi.nlm.nih.gov]
  • Megalencephaly and lissencephaly associated with defective programmed cell death from loss of CRADD function in humans implicate reduced apoptosis as an important pathophysiological mechanism of cortical malformation.[ncbi.nlm.nih.gov]
  • Role of cytoskeletal abnormalities in the neuropathology and pathophysiology of type I lissencephaly. Acta Neuropathol. 2011 Feb;121(2):149-70. doi: 10.1007/s00401-010-0768-9. Epub 2010 Nov 3. Review. Guerrini R, Parrini E.[ghr.nlm.nih.gov]

Prevention

  • Management and treatment Management is symptomatic only (swallowing problems require adapted feeding to prevent food aspiration, articular and respiratory physiotherapy to prevent orthopaedic problems resulting from hyptonia, and treatment of gastrooesophageal[orpha.net]
  • A gastric catheter or even a gastrotomy may be necessary to prevent complications linked to swallowing and feeding difficulties (malnutrition, regurgitation-induced pneumopathy).[orpha.net]
  • Lissencephaly, a disorder that affects a baby’s brain in preventing it from developing folds or grooves. A baby with Lissencephaly will be very smoothed while lacking wrinkles.[cbdreviews.net]
  • A little boy born with a rare brain disease that prevented him from being able to cry or feed properly, has died at just eight weeks old.[dailymail.co.uk]

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