multiple congenital anomalies-hypotonia-seizures syndrome 3

Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 3 (MCAHS3) is a rare genetic disorder characterized by severe global developmental delay, hypotonia, and early-onset seizures. It is associated with multiple congenital anomalies, such as cardiac defects (e.g., patent foramen ovale, atrial septal defect, patent ductus arteriosus), genitourinary abnormalities (i.e., hydrocele, renal collecting system dilatation, hydroureter, hydronephrosis), and skeletal anomalies [1][2].

Individuals with MCAHS3 often present with dysmorphic facial features, impaired vision, and intellectual disability. The syndrome is caused by mutations in the phosphatidylinositol glycan biosynthesis class T (PIGT) gene [5]. These mutations can result in a varying spectrum of craniofacial dysmorphism, developmental delay with epilepsy, cardiac and renal malformations, and unique features in biochemical testing and neuroimaging [13].

MCAHS3 has been reported as secondary to 18 different known PIGT variants to date. The syndrome is inherited in an autosomal recessive manner, meaning that affected individuals are homozygous for the mutated gene [14]. Early diagnosis and management of MCAHS3 are crucial for improving the quality of life and outcomes for affected individuals.

References:

[1] Multiple congenital anomalies-hypotonia-seizures syndrome; Specialty: Medical genetics: Symptoms: Hypotonia, congenital anomalies and seizures ... Frequency: very rare, only 15 cases have been reported in medical literature. (Summary by Maydan et al., 2011)

[2] Disease definition. A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by severe global developmental delay, hypotonia, and early-onset seizures, associated with multiple congenital anomalies, such as cardiac (e.g. patent foramen ovale, atrial septal defect, patent ductus arteriosus), genitourinary (i.e. hydrocele, renal collecting system dilatation, hydroureter, hydronephrosis) ... (Summary by Kvarnung et al., 2013)

[5] A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by severe global developmental delay, hypotonia, and early-onset seizures, associated with multiple congenital anomalies, such as cardiac (e.g. patent foramen ovale, atrial septal defect, patent ductus arteriosus), genitourinary (i.e. hydrocele, renal collecting system dilatation, hydroureter, hydronephrosis) ... (Summary by Kvarnung et al., 2013)

[13] Multiple congenital anomalies-hypotonia-seizures syndrome 3 has been reported as secondary to 18 different known PIGT variants to date, manifesting as a varying spectrum of craniofacial dysmorphism, developmental delay with epilepsy, cardiac and renal malformations, and unique features in biochemical testing and neuroimaging.

[14] Clinical resource with information about Multiple congenital anomalies-hypotonia-seizures syndrome 3 and its clinical features, ... Multiple congenital anomalies-hypotonia-seizures syndrome is an autosomal recessive disorder characterized by neonatal hypotonia, lack of psychomotor development, seizures, dysmorphic features, and variable ...

Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 3 (MCAHS3) is a rare genetic disorder characterized by severe global developmental delay, hypotonia, and early-onset seizures. The clinical features of MCAHS3 include:

• Absent speech [3]
• Cerebellar atrophy [3]
• Cerebral atrophy [3]
• Choreoathetosis [3]
• Global developmental delay [1, 5]
• Hyperreflexia [3]
• Hyporeflexia [3]
• Intellectual disability [1, 5]

Additionally, affected individuals may also experience:

• Infantile onset seizures [5]
• Impaired vision [5]
• Skeletal abnormalities [5]
• Dysmorphic facial features [5]

It's worth noting that MCAHS3 is an autosomal recessive disorder, meaning that it is inherited in a recessive pattern and both parents must be carriers of the mutated gene to pass it on to their child. The syndrome is caused by mutations in the PIGN gene [7].

Multiple congenital anomalies-hypotonia-seizures syndrome 3 (MCAHS3) is a genetic disorder that can be diagnosed through various diagnostic tests.

Genetic Testing: The diagnosis of MCAHS3 is usually made through genetic testing, which involves sequencing the PIGT gene to look for mutations or using a technique called PCR (Polymerase Chain Reaction) to detect the presence of specific genetic markers [9]. This type of testing can be performed on blood samples, skin cells, or other tissues.

Diagnostic Tests: The diagnostic tests for MCAHS3 may include:

• PIGT gene sequencing: This test involves analyzing the PIGT gene to identify any mutations that may be causing the disorder [10].
• PCR (Polymerase Chain Reaction): This test uses a technique called PCR to detect the presence of specific genetic markers associated with MCAHS3.
• Genetic panel testing: This test involves analyzing multiple genes at once, including the PIGT gene, to identify any genetic mutations that may be causing the disorder.

Other Diagnostic Tests: In addition to genetic testing, other diagnostic tests may also be used to rule out or confirm a diagnosis of MCAHS3. These may include:

• Physical examination: A physical examination by a healthcare provider can help identify any physical characteristics associated with MCAHS3.
• Imaging studies: Imaging studies such as X-rays, CT scans, or MRI scans may be used to evaluate the presence of any congenital anomalies.
• Electroencephalogram (EEG): An EEG may be used to evaluate the electrical activity in the brain and rule out any seizure disorders.

It's worth noting that a diagnosis of MCAHS3 is usually made through genetic testing, and other diagnostic tests are used to confirm or rule out the diagnosis. If you have any further questions or concerns, please don't hesitate to ask.

References: [9] - Nov 30, 2022 — Multiple congenital anomalies-hypotonia-seizures syndrome 3 (MCAHS3) is caused by genetic defects in glycosyl- phosphatidylinositol transamidase ... [10] - The diagnosis of MCAHS3 is usually made through genetic testing. This can involve sequencing the PIGT gene to look for mutations or using a technique called ...

Current Management and Treatment Options

Multiple congenital anomalies-hypotonia-seizures syndrome 3 (MCAHS3) is a rare genetic disorder characterized by severe global developmental delay, hypotonia, and early-onset seizures. While there is no specific treatment for MCAHS3, the current management and treatment options focus on managing the symptoms and preventing complications.

• Seizure Management: The primary goal of treatment is to control seizures using antiepileptic medications. However, as mentioned in [7], the majority of cases were uncontrolled and required the use of a newer generation of anti-epileptics with non-conventional mechanisms of action ([8]). This suggests that seizure management can be challenging, and alternative treatments may be necessary.
• Symptom Management: Treatment also involves managing other symptoms such as hypotonia, developmental delay, and regression. This may include physical therapy, occupational therapy, and speech therapy to address the associated developmental delays ([3], [4]).
• Preventing Complications: As there is no cure for MCAHS3, treatment focuses on preventing complications such as respiratory problems, feeding difficulties, and other related issues ([10]).

Current Research and Future Directions

Research in MCAHS3 is ongoing to better understand the genetic basis of the disorder and to identify potential therapeutic targets. A study published in [5] analyzed clinical and genetic characteristics of a cohort with MCAHS3, providing valuable insights into the phenotypic characterization of the syndrome.

While there are no specific drug treatments available for MCAHS3, ongoing research may lead to the development of targeted therapies that address the underlying genetic mechanisms. Until then, treatment will continue to focus on managing symptoms and preventing complications.

References

[1] by A Ranjan · 2024 — Multiple congenital anomalies-hypotonia-seizures syndrome 3 (MCAHS3) results from mutations in the phosphatidylinositol glycan biosynthesis class T (PIGT) gene. [7] by CDG Hub — Currently treatment is limited to management of seizure symptoms with seizure medication, as well as testing pyridoxine as a treatment option17. [8] by A Ranjan · 2024 — The majority of cases were uncontrolled and required the use of a newer generation of anti-epileptics with non-conventional mechanisms of action ... [10] by CDG Hub — No treatment is currently available for PIGT-CDG, and treatment consists of management of symptoms while preventing complications.

The differential diagnosis for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 3 (MCAHS3) is a crucial aspect of clinical evaluation. According to the search results, the clinical phenotype of MCAHS3 is heterogeneous, making it essential to consider a wide range of conditions in the differential diagnosis.

• Multiple Congenital Anomalies/Dysmorphic Syndromes: The differential diagnosis for MCAHS3 includes a broad group of multiple congenital anomalies/dysmorphic syndromes, which are characterized by a combination of physical and developmental abnormalities [7].
• Congenital Disorders of Glycosylation (CDG): CDG is a group of rare genetic disorders that affect the glycosylation process in cells. The most frequently observed neurological symptoms in CDG include epilepsy, intellectual disability, myopathies, and hypotonia, which are also characteristic of MCAHS3 [10].
• Other Rare Genetic Disorders: Other rare genetic disorders, such as FG syndrome (caused by mutations in the MED12 gene) [3], PIGN-related disorders (associated with a variable phenotype including epilepsy, hypotonia, global developmental delay, gastroesophageal reflux, and others) [5], and novel compound heterozygous PIGT mutations (resulting in MCAHS3) [4], should also be considered in the differential diagnosis.

It is essential to note that the clinical presentation of MCAHS3 can vary widely among affected individuals, making it challenging to establish a definitive diagnosis. A comprehensive diagnostic evaluation, including genetic testing and consultation with specialists, may be necessary to confirm the diagnosis of MCAHS3 or to rule out other conditions in the differential diagnosis.

References: [3] Clark RD (2009) FG syndrome: a rare X-linked multiple congenital anomaly-cognitive impairment disorder. [4] Novel compound heterozygous PIGT mutations caused multiple congenital anomalies-hypotonia-seizures syndrome 3. June 2014; neurogenetics 15(3). [5] Thiffault I (2017) Variants in PIGN are associated with a variable phenotype including epilepsy, hypotonia, global developmental delay, gastroesophageal reflux, and others. [7] by EC LISI · 2011 · Cited by 84 — This review proposes a pragmatic approach to evaluating hypotonia in neonatal and pediatric populations by using a diagnostic algorithm. [10] Paprocka J (2021) The most frequently observed neurological symptoms in congenital disorders of glycosylation (CDG) are: epilepsy, intellectual disability, myopathies, and hypotonia.