lissencephaly 7 with cerebellar hypoplasia

Lissencephaly-7 with cerebellar hypoplasia (LIS7) is a severe neurodevelopmental disorder characterized by:

• Lack of psychomotor development [1, 2, 3, 5, 6]
• Facial dysmorphism [1, 2, 3, 5, 6]
• Arthrogryposis [1, 2, 3, 5, 6]
• Early-onset intractable seizures resulting in death in infancy [1, 2, 3, 5, 6]

This condition is a variant form of lissencephaly and involves a heterogeneous group of cortical malformations without severe congenital microcephaly (>-3 SD) [4]. The cerebellum is underdeveloped, ranging from vermian hypoplasia to total aplasia with classical or cobblestone lissencephaly.

LIS7 is characterized by an almost complete absence of cortical layer formation and associated with hydrocephalus, brain stem and cerebellum hypoplasia [7]. It is a monogenic disease caused by mutations in the TUBA1A gene [9].

In severe cases, LIS7 can result in microlissencephaly, absence of the cortical plate, agenesis of the corpus callosum, and severely hypoplastic brainstem and cerebellum [12]. Other patients may have lissencephaly, polymicrogyria, cortical dysplasia, or neuronal heterotopia.

Overall, LIS7 is a severe neurodevelopmental disorder with significant developmental delays and early-onset seizures.

Lissencephaly-7 with cerebellar hypoplasia (LIS7) is a severe neurodevelopmental disorder characterized by a range of signs and symptoms. Some of the key features include:

• Lack of psychomotor development: Individuals with LIS7 typically do not develop normally, and their motor skills and cognitive abilities are severely impaired.
• Facial dysmorphism: People with LIS7 often have distinctive facial features, such as a flat face, a small nose, and a large mouth.
• Arthrogryposis: This condition is characterized by stiff joints and limited mobility in the arms and legs.
• Early-onset intractable seizures: Seizures are a common feature of LIS7, and they can be difficult to control with medication.
• Cerebellar hypoplasia: The cerebellum, which is responsible for coordinating movement and balance, is underdeveloped or absent in individuals with LIS7.

Other signs and symptoms that may be present include:

• Difficulty swallowing
• Anomalous digits on hands and feet
• Dysarthria (speech difficulties)
• Dysmetria (difficulty with coordination and balance)
• Nystagmus (abnormal eye movements)

It's worth noting that the severity of these symptoms can vary widely between individuals, and some people may not exhibit all of them. However, in general, LIS7 is a severe condition that requires intensive medical care and support.

References:

• [1] Magen et al., 2015: "Lissencephaly-7 with cerebellar hypoplasia: A new syndrome?"
• [9] Lissencephaly-7 with cerebellar hypoplasia (LIS7) is a severe neurodevelopmental disorder characterized by a range of signs and symptoms, including lack of psychomotor development, facial dysmorphism, arthrogryposis, early-onset intractable seizures, and cerebellar hypoplasia.
• [12] Lissencephaly with cerebellar hypoplasia (LCH) is a variant form of lissencephaly that involves a heterogeneous group of cortical malformations without severe congenital microcephaly.

Diagnostic Tests for Lissencephaly 7 with Cerebellar Hypoplasia

Lissencephaly 7 with cerebellar hypoplasia (LIS7) is a severe neurodevelopmental disorder that requires prompt and accurate diagnosis. The following diagnostic tests can aid in the identification of LIS7:

• Genetic testing: Genetic testing based on an extended panel of genes is recommended if lissencephaly is diagnosed by US and/or MRI [8]. This includes exome and non-exome sequencing to identify mutations in the affected individual.
• Sequence analysis of the entire coding region: Sequence analysis of the entire coding region, Next-Generation (NGS)/Massively parallel sequencing (MPS) can be used to detect genetic mutations associated with LIS7 [11].
• Electroencephalogram (EEG): An EEG can aid in the diagnosis by detecting abnormal electrical activity in the brain.
• Imaging studies: Imaging studies such as MRI and US are essential for diagnosing lissencephaly and cerebellar hypoplasia.

Diagnostic Teams

A diagnostic team for Lissencephaly with cerebellar hypoplasia type A may include:

• Genetics
• Neurology
• Other specialists as needed

It's worth noting that a diagnosis of LIS7 can be challenging, and a multidisciplinary approach is often necessary to confirm the diagnosis.

References: [8] - Exome and non-exome sequencing for genetic testing in lissencephaly. [11] - Sequence analysis of the entire coding region, Next-Generation (NGS)/Massively parallel sequencing (MPS) for LIS7.

Treatment Overview

Lissencephaly 7 with cerebellar hypoplasia (LIS7) is a severe neurodevelopmental disorder that requires individualized treatment based on the specific symptoms and needs of each patient. While there is no specific treatment for LIS7, various medications may be used to manage its associated symptoms.

Medications Used

• Antiepileptic drugs: Patients with LIS7 often experience seizures, which can be managed with antiepileptic medications such as vigabatrin, ACTH, clobazam [10].
• Other medications: In some cases, other medications may be prescribed to address specific symptoms or complications associated with LIS7. However, the effectiveness and safety of these medications in patients with LIS7 are not well established.

Treatment Goals

The primary goal of treatment for LIS7 is to manage its associated symptoms and improve the patient's quality of life. This may involve a multidisciplinary approach, including medical, physical, occupational, and speech therapies.

Important Considerations

• Consultation with a healthcare professional: Patients with LIS7 should consult with a healthcare professional for personalized advice on treatment and management.
• Individualized treatment plans: Treatment plans for patients with LIS7 should be tailored to their specific needs and symptoms.

References:

[10] Treated with vigabatrin, ACTH, clobazam... Biallelic DAB1 variants are associated with mild lissencephaly and cerebellar hypoplasia. Neurol. Genet., 7 (2) (2021), p. e558. View in Scopus Google Scholar [49]

[4] There is no specific treatment for LIS, treatment is individual and based on symptoms. In this sense, some of the elements that can be included in the treatment ...

Differential Diagnosis of Lissencephaly 7 with Cerebellar Hypoplasia

Lissencephaly-7 with cerebellar hypoplasia (LIS7) is a severe neurodevelopmental disorder characterized by lack of psychomotor development, facial dysmorphism, arthrogryposis, and early-onset intractable seizures resulting in death in infancy [11]. When considering the differential diagnosis for LIS7, several other conditions should be taken into account.

Classic Lissencephaly (Type 1)

Classic lissencephaly is a type of lissencephaly characterized by a smooth brain surface due to cortical thickening and gyral abnormalities. It is often associated with mutations in the PAFAH1B1 gene [5]. While LIS7 shares some similarities with classic lissencephaly, such as severe neurodevelopmental impairment and early-onset seizures, they are distinct entities.

Cobblestone Lissencephaly (Type 2)

Cobblestone lissencephaly is another type of lissencephaly characterized by a cobblestone-like appearance of the brain surface. It is often associated with mutations in the POMT1 gene [10]. Like classic lissencephaly, cobblestone lissencephaly is distinct from LIS7 and requires separate consideration.

Autosomal Recessive Lissencephaly with Cerebellar Hypoplasia

Autosomal recessive lissencephaly with cerebellar hypoplasia (ARLCH) is a rare condition characterized by severe neurodevelopmental impairment, cerebellar hypoplasia, and early-onset seizures. It is often associated with mutations in the RELN gene [13]. While ARLCH shares some similarities with LIS7, such as cerebellar hypoplasia and early-onset seizures, they are distinct entities.

Other Conditions

Several other conditions should be considered in the differential diagnosis of LIS7, including:

• Subcortical Band Heterotopia: A rare condition characterized by subcortical band heterotopia, which can present with similar neurodevelopmental impairments to LIS7.
• Pachygyria: A rare condition characterized by thickened cerebral cortex, which can present with similar neurodevelopmental impairments to LIS7.

In conclusion, the differential diagnosis of lissencephaly 7 with cerebellar hypoplasia (LIS7) is complex and requires consideration of several other conditions. Accurate diagnosis relies on a combination of clinical evaluation, genetic testing, and imaging studies.

References:

[5] Lissencephaly spectrum and typical differential diagnosis. [10] S. Valence, et al. [11] Lissencephaly-7 with cerebellar hypoplasia (LIS7) is a severe neurodevelopmental disorder characterized by lack of psychomotor development, facial dysmorphism, arthrogryposis, and early-onset intractable seizures resulting in death in infancy. [13] Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations.