primary autosomal recessive microcephaly 15

Primary autosomal recessive microcephaly (PMCPH) is a rare genetic disorder characterized by a significantly small head size and intellectual disability.

Causes and Symptoms

• PMCPH is caused by mutations in the ASPM, CENPJ, CDK2AP1, and CEP135 genes [1].
• The condition is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the disorder [2].
• Symptoms typically become apparent at birth or during early childhood and may include:
  • Microcephaly: A head circumference significantly smaller than average for age and sex [3].
  • Intellectual disability: Ranging from mild to severe, depending on the severity of the genetic mutation [4].
  • Developmental delays: Children with PMCPH may experience delays in reaching developmental milestones, such as sitting, standing, or walking [5].

Diagnosis and Treatment

• Diagnosis is typically made through a combination of clinical evaluation, genetic testing (such as DNA sequencing), and imaging studies (e.g., MRI) to confirm the presence of microcephaly and rule out other conditions [6].
• There is no specific treatment for PMCPH, but supportive care and management strategies can help improve quality of life. These may include:
  • Early intervention programs: To address developmental delays and promote cognitive development.
  • Speech and language therapy: To support communication skills.
  • Physical therapy: To enhance motor function and mobility.

Prognosis

• The prognosis for individuals with PMCPH varies depending on the severity of the genetic mutation and the effectiveness of supportive care. Some people may experience significant intellectual disability, while others may have milder symptoms [7].

References:

[1] ASPM gene mutations: https://www.ncbi.nlm.nih.gov/pubmed/15707855 [2] Autosomal recessive inheritance pattern: https://ghr.nlm.nih.gov/primer/inheritance/autosomerecessive [3] Microcephaly definition: https://www.merriam-webster.com/dictionary/microcephaly [4] Intellectual disability spectrum: https://www.cdc.gov/ncbddd/disabilityandhealth/index.html [5] Developmental delays: https://www.healthychildren.org/English/ages-stages/babies/Pages/Developmental-Delays.aspx [6] Diagnostic criteria for PMCPH: https://www.ncbi.nlm.nih.gov/pubmed/25540955 [7] Prognosis and supportive care: https://www.ncbi.nlm.nih.gov/pubmed/28684451

Based on the provided context, here are the signs and symptoms of primary autosomal recessive microcephaly (MCPH):

• Reduced head circumference at birth [4]
• Variable degree of mental retardation [4]
• Absent speech [1]
• Autistic behavior [1]
• Cerebellar ataxia [1]
• Cerebellar hypoplasia [1]
• Global developmental delay [1]
• Hyperreflexia [1]
• Hypoplasia of the brain [1]

Additionally, some patients may experience:

• Seizures [2]
• Lack of developmental milestones [2]
• Early death [2]
• Short stature [3]
• Mild seizures [3]
• Simplification of the cerebral cortical gyral pattern [3]
• Intellectual impairment [7]
• Delayed speech and motor skills [7]

Please note that these symptoms may vary in severity and presentation, and not all individuals with MCPH will exhibit all of these signs.

Based on the provided context, here are some diagnostic tests associated with primary autosomal recessive microcephaly (MCPH):

• Head Circumference Measurement: This is the most common diagnostic tool for MCPH. Head circumference (HC) or occipitofrontal circumference (OFC) is measured to assess whether it falls within the normal range or if there's a significant reduction, indicating MCPH [5].
• Genetic Testing: Specific genes associated with MCPH can be tested to confirm the diagnosis. For instance, testing for the ANKLE2 gene is one of the 16 genes that can be analyzed in relation to this condition [6].

It's essential to note that a comprehensive diagnostic approach may involve a combination of clinical evaluation, genetic testing, and other assessments to rule out other potential causes of microcephaly. A detailed medical history, physical examination, and imaging studies (such as MRI or CT scans) might also be part of the diagnostic process.

References: [5] - Head circumference measurement is mentioned in [5], which states that HC ranges are observed for MCPH. [6] - Genetic testing, specifically ANKLE2 gene analysis, is listed among the 16 genes tested for conditions (1): Autosomal recessive primary microcephaly.

Treatment Overview

Primary autosomal recessive microcephaly (MCPH) is a rare genetic disorder that affects brain development, leading to a small head size and potentially severe cognitive impairments. While there is no cure for MCPH, various treatments can help manage its symptoms and improve the quality of life for affected individuals.

Drug Treatment

While specific drug treatment options are not mentioned in the search results, it's essential to note that seizures associated with MCPH can be stabilized using common anticonvulsants (1). However, there is no specific etiologic treatment for MCPH itself (3).

Multidisciplinary Care

A multidisciplinary team, often including a pediatric neurologist and developmental pediatrician, speech-language pathologist, and other specialists, can provide comprehensive care for individuals with MCPH (4). This team approach helps address various aspects of the condition, such as seizures, cognitive impairments, and physical disabilities.

No Cure

It's crucial to emphasize that there is no treatment for MCPH that will return the baby's head to a normal size or shape. Microcephaly is a lifelong condition with no cure (5, 7, 9). Therefore, treatment focuses on managing symptoms, improving quality of life, and providing supportive care.

References

• [1] Clinical trials determine if a new test or treatment for a disease is effective and safe by comparing groups receiving different tests/treatments.
• [3] There is no specific etiologic treatment. Physical and speech therapy may be beneficial. Seizures are usually stabilized with common anticonvulsants. Ritalin ...
• [4] Feb 17, 2022 — Treatment is symptomatic. Care by a multidisciplinary team, often including a pediatric neurologist, developmental pediatrician, speech-language ...
• [5] How is microcephaly treated in a child? ... There is no treatment for microcephaly that will return the baby's head to a normal size or shape. Microcephaly is a ...
• [7] There is no treatment for microcephaly that will return the baby's head to a normal size or shape. Microcephaly is a lifelong condition that has no cure.
• [9] There is no treatment for microcephaly that will return the baby's head to a normal size or shape. Microcephaly is a lifelong condition that has no cure.

Differential Diagnosis of Primary Autosomal Recessive Microcephaly

Primary autosomal recessive microcephaly (MCPH) is a rare neurodevelopmental disorder characterized by reduced head circumference at birth, with no major brain abnormalities. When diagnosing MCPH, it's essential to consider differential diagnoses that can mimic its symptoms.

Key Differential Diagnoses:

• Microcephalic forms of Seckel syndrome: This condition shares similarities with MCPH, including microcephaly and intellectual disability.
• Other primary microcephalies: These conditions, such as autosomal dominant primary microcephaly (MCPHD), can also present with reduced head circumference at birth.

Diagnostic Considerations:

When diagnosing MCPH, it's crucial to rule out other conditions that may present with similar symptoms. This includes:

• Imaging studies: Neuroimaging techniques like ultrasound and MRI are useful for differential diagnosis in patients with primary microcephaly.
• Genetic testing: Identifying pathogenic variants in genes associated with MCPH can confirm the diagnosis.

References:

• [3] Most primary microcephalies are inherited in an autosomal recessive manner. To date, pathogenic variants in more than 100 genes are known to cause this condition.
• [5] Neuroimaging of the brain with ultrasound and/or MRI are useful for the differential diagnosis in patients with primary microcephaly.
• [9] Autosomal recessive primary microcephaly (MCPH) is a rare disorder characterized by reduced head circumference at birth, with no major brain abnormalities.