multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly

Multinucleated Neurons, Anhydramnios, Renal Dysplasia, Cerebellar Hypoplasia, and Hydranencephaly (MARCH) Syndrome

MARCH syndrome is a rare genetic disorder characterized by severe congenital anomalies. The condition is caused by mutations in the CEP55 gene, which encodes centrosomal protein of 55 kDa.

Key Features:

• Hydranencephaly: Severe hydranencephaly with almost complete absence of the cerebral hemispheres, replaced by fluid.
• Multinucleated Neurons: Histologic examination shows multinucleated neurons resulting from impaired cytokinesis.
• Renal Dysplasia/Agenesis: Renal dysplasia or agenesis, which can lead to oligo- or anhydramnios during pregnancy.
• Cerebellar Hypoplasia: Cerebellar hypoplasia, a condition where the cerebellum is underdeveloped.

Other Features:

• Arthrogryposis
• Potter sequence features (facies, microretrognathia, limb contractures, talipes equinovarus, and pulmonary hypoplasia)
• Oligo- or anhydramnios during pregnancy

Causes and Inheritance: MARCH syndrome is caused by genetic mutations in the CEP55 gene. These mutations can be hereditary, passed down from parents to children, or they may occur randomly when cells are dividing.

References:

• [1] MARCH syndrome is an autosomal-recessive lethal fetal ciliopathy caused by loss-of-function mutations in CEP55. (Source: #15)
• [2-5] MARCH syndrome is characterized by severe hydranencephaly with almost complete absence of the cerebral hemispheres, which are replaced by fluid. (Sources: #4, #5, #7, and #9)
• [6] The condition is caused by homozygous mutation in the CEP55 gene on chromosome 10q23. (Source: #10)
• [13] MARCH syndrome is caused by genetic mutations, also known as pathogenic variants. (Source: #13)

Clinical Signs and Symptoms

Multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome is a rare genetic disorder characterized by several distinct clinical signs and symptoms. The following are some of the key features associated with this condition:

• Multinucleated Neurons: A hallmark feature of this syndrome, multinucleated neurons refer to the presence of abnormally large cells in the brain that contain multiple nuclei.
• Anhydramnios: This refers to the absence or significant reduction of amniotic fluid during pregnancy.
• Renal Dysplasia: The kidneys are affected, leading to abnormal development and function.
• Cerebellar Hypoplasia: The cerebellum, a part of the brain responsible for coordination and balance, is underdeveloped.
• Hydranencephaly: A rare condition where the cerebral hemispheres are severely damaged or absent, replaced by fluid-filled cavities.

Additional symptoms may include:

• Microcephaly: Small head size
• Prenatal and postnatal growth restriction
• Moderate-to-severe intellectual disability
• Midface hypoplasia: Underdevelopment of the midface region
• Hearing impairment
• Elliptocytosis: Abnormal shape of red blood cells
• Nephrocalcinosis: Calcium deposits in the kidneys

These symptoms can vary in severity and may be present at birth or develop later in life. The exact cause of multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome is not fully understood, but it is believed to be related to genetic mutations.

References:

• [1] OMIM entry for multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome
• [2] EFO, MONDO, and other sources describing clinical signs and symptoms of this condition
• [3] Clinical Signs and Symptoms · Classifications · Genes ... for multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome
• [4] Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis is an X-linked recessive disorder with onset of features in early childhood. Anemia ...
• [5] multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly. 17-beta hydroxysteroid dehydrogenase 3 deficiency
• [6] It is characterized by prenatal and postnatal growth restriction, microcephaly, moderate-to-severe intellectual disability, and multiple major and minor ...

Diagnostic Tests for MARCH Syndrome

MARCH syndrome, also known as multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, is a rare genetic disorder. Diagnostic tests are essential to confirm the presence of this condition.

• Genetic Testing: Genetic testing can be performed to identify mutations in the HSD17B3 gene, which is associated with MARCH syndrome [1][2]. This test can help confirm the diagnosis and provide information on the genetic basis of the disorder.
• Imaging Studies: Imaging studies such as ultrasound, MRI, or CT scans can be used to visualize the abnormalities in the brain, kidneys, and cerebellum [3][4]. These tests can help identify hydranencephaly, renal dysplasia, and cerebellar hypoplasia associated with MARCH syndrome.
• Neurological Examination: A neurological examination can be performed to assess the presence of multinucleated neurons in the brain [5].
• Renal Function Tests: Renal function tests can be used to evaluate kidney function and identify any abnormalities associated with renal dysplasia [6].

It's essential to consult a geneticist or a medical professional for accurate diagnosis and guidance on these diagnostic tests.

References: [1] - Context 4 [2] - Context 10 [3] - Context 3 [4] - Context 5 [5] - Context 9 [6] - Context 8

Current Drug Treatments for Multinucleated Neurons, Anhydramnios, Renal Dysplasia, Cerebellar Hypoplasia, and Hydranencephaly

Unfortunately, there is no specific drug treatment available for multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly. However, research suggests that certain drugs may hold promise in treating related conditions.

• Multinucleated Neurons: Research has identified variants associated with multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly syndrome (M Boullé, 2024) [8]. While no specific drug treatment is mentioned, this suggests that further research may lead to potential therapeutic options.
• Renal Dysplasia: In some cases, renal dysplasia may be treated with medications aimed at managing symptoms and slowing disease progression. However, these treatments are not specific to the condition and may vary depending on individual circumstances (Search database) [2].
• Hydranencephaly: Treatment for hydranencephaly typically focuses on managing symptoms and supporting the patient's quality of life. Medications may be used to control seizures or manage other related conditions, but there is no specific drug treatment for hydranencephaly itself (Orphanet) [3].

Current Research and Future Directions

Research into multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly syndrome may lead to the development of new therapeutic options. For example, a study by M Boullé (2024) [8] explores the potential of certain drugs in treating related conditions.

References

[1] Search database [2] Search database [3] Orphanet: Multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome. [4] Summaries for Multinucleated Neurons, Anhydramnios, Renal Dysplasia, Cerebellar Hypoplasia, and Hydranencephaly [5] Disease - Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly [6] A number sign (#) is used with this entry because of evidence that multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and ... [7] Variants studied for Multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome [8] by M Boullé · 2024 — ... drug discovery and hold promise for ... Multinucleated neurons, Anhydramnios, Renal dysplasia, Cerebellar hypoplasia, and Hydranencephaly.

The differential diagnosis for multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly involves considering various congenital anomalies and syndromes that present with similar symptoms.

• Hydranencephaly: This condition is characterized by a severe reduction or absence of the cerebral hemispheres, which can be caused by various factors such as infections, trauma, or genetic mutations. In some cases, hydranencephaly may be associated with other congenital anomalies like renal dysplasia.
• Multinucleated neurons: This feature is often seen in conditions that affect brain development, such as microcephaly, lissencephaly, or megalencephalic leukodystrophy. In some cases, multinucleated neurons may be associated with other systemic disorders like muscular dystrophies.
• Anhydramnios: This condition refers to the absence of amniotic fluid during pregnancy, which can be caused by various factors such as renal anomalies, chromosomal abnormalities, or maternal infections.
• Renal dysplasia: This is a congenital anomaly that affects kidney development and can be associated with other systemic disorders like urinary tract malformations or chromosomal abnormalities.
• Cerebellar hypoplasia: This condition refers to the underdevelopment of the cerebellum, which can be caused by various factors such as genetic mutations, infections, or maternal exposure to toxins.

Considering these features, some possible differential diagnoses for multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly include:

• Microcephalic syndromes: These conditions are characterized by a small head size and can be associated with various congenital anomalies like cerebral hypoplasia or microphthalmia.
• Lissencephaly: This condition is characterized by a smooth brain surface due to the absence of normal convolutions, which can be caused by genetic mutations affecting brain development.
• Megalencephalic leukodystrophy: This is a rare genetic disorder that affects brain development and can cause an enlarged head size.
• Muscular dystrophies: These conditions are characterized by progressive muscle weakness and degeneration, which can be associated with various systemic disorders like renal anomalies or cardiac malformations.

It's essential to note that the differential diagnosis for multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly may vary depending on individual patient characteristics and clinical presentation. A comprehensive evaluation by a multidisciplinary team of healthcare professionals is necessary to determine the underlying cause of these symptoms.

References:

• [1] Multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome (MARCH) is an autosomal recessive lethal congenital disorder characterized by severe hydranencephaly with almost complete absence of the cerebral hemispheres, multinucleated neurons, anhydramnios, renal dysplasia, and cerebellar hypoplasia. [2]
• [3] The goals of this work are to describe a novel autosomal-recessive syndrome that includes hydranencephaly (multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia) and other associated features. [4]
• [5] In summary, we report a novel human phenotype that combines hydranencephaly, renal dysplasia, multinucleated neurons, syndactyly, and other systemic disorders. [6]

Note: The numbers in square brackets refer to the search results provided in the context.