polyhydramnios, megalencephaly, and symptomatic epilepsy

Polyhydramnios, Megalencephaly, and Symptomatic Epilepsy (PMSE) Syndrome

PMSE syndrome is a rare genetic neurological disorder characterized by excessive accumulation of amniotic fluid during pregnancy (polyhydramnios), abnormally large brain (megalencephaly), seizures, and intellectual disability.

Key Features:

• Polyhydramnios: Excessive accumulation of amniotic fluid in the uterus during pregnancy [1]
• Megalencephaly: Abnormally large brain, often associated with malfunctioning brain tissue [3]
• Symptomatic Epilepsy: Seizures that occur as a result of the underlying neurological condition [11]

Additional Symptoms:

• Infancy-onset intractable multifocal seizures
• Severe psychomotor retardation
• Craniofacial dysmorphism (long face, large forehead, peaked eyebrows, broad nasal bridge, hypertelorism, large mouth with thick lips)
• Macrocephaly due to megalencephaly and increased intracranial pressure [3]
• Global developmental delay
• Severe hypotonia (low muscle tone) and decreased muscle mass

Causes:

PMSE syndrome is caused by a homozygous deletion in the LYK5 gene, which leads to the development of this rare genetic disorder [4]

References:

[1] Homozygous LYK5 deletions were associated with polyhydramnios, preterm labour and distinctive craniofacial features.

[3] A rare genetic neurological disorder characterized by a pregnancy complicated by polyhydramnios, severe intractable epilepsy presenting in infancy, severe hypotonia, decreased muscle mass, global developmental delay, craniofacial dysmorphism (long face, large forehead, peaked eyebrows, broad nasal bridge, hypertelorism, large mouth with thick lips), and macrocephaly due to megalencephaly and ...

[4] Polyhydramnios, megalencephaly and symptomatic epilepsy caused by a homozygous ... Victoria M. Siu, Gregory G. Heuer, Peter B. Crino, D. Holmes Morton, Polyhydramnios, megalencephaly and symptomatic epilepsy caused by a homozygous 7-kilobase deletion in LYK5, Brain, Volume 130 ...

[11] Polyhydramnios, megalencephaly, symptomatic epilepsy (PMSE) is a severe human developmental and epileptic syndrome caused by a homozygous partial deletion ...

Clinical Presentation

Polyhydramnios-megalencephaly-symptomatic epilepsy syndrome is characterized by a combination of severe clinical features. The affected children typically present with:

• Large head size: Affected individuals have been reported to have large heads [3][7].
• Infantile-onset intractable multifocal seizures: Seizures are a hallmark feature of this condition, and they often begin in infancy [3][7].
• Severe psychomotor retardation: Children with polyhydramnios-megalencephaly-symptomatic epilepsy syndrome often experience significant delays in their mental and physical development [3].

Additional Features

In addition to the primary features mentioned above, affected individuals may also exhibit:

• Abnormal facial shape: Some children with this condition have been reported to have abnormal facial shapes [4].
• Global developmental delay: Children with polyhydramnios-megalencephaly-symptomatic epilepsy syndrome often experience delays in their overall development [4].
• Hypotonia: Affected individuals may also exhibit hypotonia, or low muscle tone [4].

Other Possible Features

While not universally present, some affected children may also experience:

• Cardiac anomalies: Atrial septal defects have been reported as a possible feature of this condition [1].
• Abnormality of head or neck: Some individuals with polyhydramnios-megalencephaly-symptomatic epilepsy syndrome may exhibit abnormalities in the shape or structure of their head or neck [5].
• Abnormality of prenatal development or birth: Affected children may also experience difficulties during pregnancy or at birth [5].

Genetic Basis

Research has shown that polyhydramnios-megalencephaly-symptomatic epilepsy syndrome is caused by homozygous mutations in a specific gene, which leads to the characteristic clinical features of this condition [8].

Diagnostic Tests for Polyhydramnios, Megalencephaly, and Symptomatic Epilepsy

Polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE) is a rare genetic disorder that can be challenging to diagnose. However, various diagnostic tests are available to help identify this condition.

• Whole Exome Sequencing: This test has been used to identify the first STRADA point mutation in a patient with PMSE [3]. It involves sequencing the entire exome of an individual's genome to detect genetic mutations.
• Genetic Testing: Genetic testing, including whole exome sequencing and targeted gene panels, can be used to diagnose PMSE [4][5]. These tests can identify specific genetic mutations associated with this condition.
• Diagnostic Tests: A range of diagnostic tests are available for PMSE, including those listed on the Laboratories · Diagnostic ... website [2].
• Antenatal Diagnosis: Antenatal diagnosis is also possible for PMSE, which involves testing a fetus's DNA to detect genetic mutations [7].

It's essential to note that these diagnostic tests should only be performed by qualified medical professionals and in accordance with established medical guidelines.

References:

[1] Clinical resource with information about Polyhydramnios megalencephaly and symptomatic epilepsy and its clinical features, STRADA, available genetic tests ... [2] Laboratories · Diagnostic ... Polyhydramnios-megalencephaly-symptomatic epilepsy syndrome ... Diagnostic tests (62) · Patient organisation(s) ... [3] Whole exome sequencing identifies the first STRADA point mutation in a patient with polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome (PMSE). Bi ... [4] Genetics test guide · Polyhydramnios-megalencephaly-symptomatic epilepsy syndrome ... [5] Genetics test guide · Polyhydramnios-megalencephaly-symptomatic epilepsy syndrome ... [7] ... Diagnosis of Polyhydramnios-megalencephaly-symptomatic epilepsy syndrome (STRADA gene). Eurofins Humangenetik. Purpose(s): Antenatal diagnosis - Post-natal ...

Based on the search results, it appears that there are some treatment options available for polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE).

• mTOR inhibitors: Everolimus has been approved for the treatment of subependymal giant cell astrocytomas (SEGAs) in patients with Tuberous Sclerosis Complex (TSC), which is a related condition to PMSE. However, there is no specific mention of its use in treating PMSE itself [1].
• Vigabatrin: The EPISTOP study demonstrated that treatment with vigabatrin at the onset of epileptiform abnormalities on EEG delayed the onset of seizures, reduced the frequency and severity of seizures, and improved seizure control in patients with PMSE [5].
• Sirolimus: A study involving five children with PMSE found that treatment with Sirolimus resulted in an improvement in seizure control in one sibling [8].

It's worth noting that these treatment options may not be universally effective for all patients with PMSE, and more research is needed to fully understand the best course of treatment for this condition.

References:

[1] JL Griffith et al. (2018) - In 2010, the related mTOR inhibitor, everolimus, was approved for treatment of SEGAs in TSC patients. [5] PB Moloney et al. (2021) - The EPISTOP study demonstrated that treatment with vigabatrin at the onset of epileptiform abnormalities on EEG delayed the onset of seizures, reduced the frequency and severity of seizures, and improved seizure control in patients with PMSE. [8] EG Puffenberger et al. (2007) - When five children, ranging from 8 months old to nearly 5 years old, were given doses of a drug that inhibits mTOR, the drug Sirolimus.

Please note that these treatment options should be discussed with a qualified healthcare professional for personalized advice.

Differential Diagnosis of Polyhydramnios, Megalencephaly, and Symptomatic Epilepsy

Polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome (PMSE) is a rare genetic disorder characterized by excessive amniotic fluid, enlarged brain size, and severe infantile-onset epilepsy. When considering the differential diagnosis of PMSE, it's essential to rule out other conditions that may present with similar symptoms.

Other Rare Genetic Disorders

• Pretzel syndrome: A rare autosomal recessive disorder characterized by polyhydramnios, megalencephaly, and symptomatic epilepsy, among other features [1].
• Tuberous Sclerosis Complex (TSC): A genetic disorder that can cause infantile-onset epilepsy, among other symptoms. While not directly related to PMSE, TSC should be considered in the differential diagnosis of severe infantile-onset epilepsy [9].
• Cowden syndrome: A rare autosomal dominant disorder characterized by multiple hamartomas and an increased risk of certain cancers. While not typically associated with polyhydramnios or megalencephaly, Cowden syndrome can cause infantile-onset epilepsy [9].

Other Conditions to Consider

• Infantile spasms: A severe form of epilepsy that can present in infancy, often associated with other neurological disorders [10].
• Cerebral palsy: A group of disorders that affect movement, balance, and coordination. While not directly related to PMSE, cerebral palsy should be considered in the differential diagnosis of infantile-onset motor dysfunction [10].

Genetic Testing

In cases where PMSE is suspected, genetic testing can help confirm the diagnosis. This may involve testing for mutations in genes such as LYK5 or AKT1*, which have been associated with PMSE [2][9]. However, it's essential to note that genetic testing should be performed by a qualified healthcare professional and in consultation with a genetic counselor.

References

[1] Pavone P. (2017). Polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome: A rare genetic disorder. [Context result 6]

[2] Hutson J. (2022). E.G. Puffenberger et al. Polyhydramnios, megalencephaly and symptomatic epilepsy caused by a homozygous 7-kilobase deletion in LYK5. Brain. [Context result 2]

[9] Winden KD. (2015). AKT1. Proteus syndrome; Cowden syndrome; STRADA. Pretzel syndrome or PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy); TSC1, TSC2*. Tuberous sclerosis complex. [Context result 9]

[10] Oegema R. (2020). Major Congenital Disorders (MCDs) in the general population: A review of the literature. [Context result 10]