primary autosomal recessive microcephaly 4

Primary autosomal recessive microcephaly 4 (MCPH4) is a rare genetic disorder characterized by a very small head and brain size at birth, intellectual disability, and developmental delays.

Key Features:

• Small Head Size: Infants born with MCPH4 have a significantly smaller head circumference compared to the average population mean.
• Intellectual Disability: Affected individuals often experience nonprogressive mental retardation, which means their cognitive abilities remain impaired throughout life.
• Developmental Delays: Children with MCPH4 may exhibit delays in reaching developmental milestones, such as sitting, walking, or talking.

Genetic Cause: MCPH4 is caused by mutations in the CASC5 gene (KNL1; 609173) on chromosome 15q15. This genetic mutation leads to impaired neurogenesis and brain development during fetal growth.

Clinical Diagnosis: A diagnosis of MCPH4 is made when an individual has a head circumference more than 3 standard deviations below the age- and sex-matched population mean, accompanied by mental retardation, with no other associated malformations and without apparent etiology.

References:

• [1] Description. Autosomal recessive primary microcephaly (often shortened to MCPH, which stands for "microcephaly primary hereditary") is a condition in which infants are born with a very small head and a small brain.
• [3] Primary microcephaly (MCPH) is a clinical diagnosis made when an individual has a head circumference more than 3 standard deviations below the age- and sex-matched population mean and mental retardation, with no other associated malformations and with no apparent etiology.
• [5] Apr 1, 2011 — The reduced brain size underlies the small head size, intellectual disability, and developmental delays seen in many affected individuals.

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

Common Features

• Microcephaly present at birth (congenital) [6]
• Reduced head circumference at birth with variable degree of mental retardation [4]
• Intellectual impairment [9]

Developmental Delays

• Delayed speech and language development [2][7]
• Global developmental delay [2]
• Delay in early motor milestones, such as sitting, standing, and walking [1][7]

Other Features

• Aggressive behavior [2]
• Bimanual synkinesia (a neurological disorder characterized by involuntary movements of the hands) [2]
• Cerebellar vermis hypoplasia (a condition where the cerebellum is underdeveloped) [2]

Please note that these symptoms may vary in severity and presentation among individuals with MCPH.

Based on the provided context, here are the diagnostic tests for primary autosomal recessive microcephaly 4 (MCPH4):

• Genetic Testing: Genetic testing is a crucial step in diagnosing MCPH4. This can include exome sequencing with CNV detection (as mentioned in search result [8]) to identify any genetic mutations associated with the condition.
• Head Circumference Measurement: Measuring head circumference is a common diagnostic tool for MCPH, as it has been observed that HC ranges from 3-5 standard deviations below the mean (search result [14]). This measurement can help confirm the diagnosis of MCPH4.
• Intellectual Disability Assessment: Assessing intellectual disability is also an essential part of diagnosing MCPH4. This can involve evaluating cognitive function and developmental milestones to determine if there are any signs of intellectual impairment (search results [10] and [12]).
• Exome Sequencing with CNV Detection: Exome sequencing with CNV detection is a specific genetic testing method that can help identify the underlying genetic cause of MCPH4. This test can detect deletions or duplications in genes associated with the condition (search result [8]).

It's worth noting that establishing care with an engaged and dedicated primary care provider (PCP) may improve care and shorten the time it takes to reach an accurate diagnosis (search result [11]). A PCP can help coordinate providers, order diagnostic tests, and provide overall care for individuals with MCPH4.

Based on the search results, it appears that there is no specific etiologic treatment for primary autosomal recessive microcephaly (MCPH). However, seizures associated with MCPH can be stabilized with common anticonvulsants.

• Seizures are usually stabilized with common anticonvulsants [1].
• Physical and speech therapy may also be beneficial in managing the condition [1].

It's worth noting that there is no treatment available to return the baby's head to a normal size or shape, as microcephaly is a lifelong condition with no cure [4][6][7]. However, early intervention and management through physical and speech therapy can help improve the quality of life for individuals with MCPH.

References: [1] - Search result 1 [4] - Search result 4 [6] - Search result 6 [7] - Search result 7

Differential Diagnosis of Primary Autosomal Recessive Microcephaly (MCPH)

Primary autosomal recessive microcephaly (MCPH) is a rare neurodevelopmental disorder characterized by reduced head circumference at birth, with no major brain abnormalities. The differential diagnosis for MCPH involves ruling out other conditions that may present with similar symptoms.

Conditions to Consider:

• Microcephalic disorders: Other genetic conditions that result in microcephaly, such as lissencephaly or megalencephalic leukodystrophy.
• Neurodevelopmental disorders: Conditions like intellectual disability, autism spectrum disorder, or developmental delay, which may present with similar symptoms to MCPH.
• Infections and metabolic disorders: Certain infections (e.g., congenital toxoplasmosis) or metabolic disorders (e.g., phenylketonuria) that can cause microcephaly.

Diagnostic Tools:

• Neuroimaging: Ultrasound, MRI, or CT scans may be used to rule out other conditions and confirm the diagnosis of MCPH.
• Genetic testing: Molecular genetic analysis can help identify mutations in genes associated with MCPH.

References:

• [7] Autosomal recessive primary microcephaly (MCPH) is a rare disorder characterized by reduced head circumference at birth, with no major brain abnormalities. It ...
• [5] by S Zaqout · 2017 · Cited by 93 — Neuroimaging of the brain with ultrasound and/or MRI are useful for the differential diagnosis in patients with primary microcephaly.
• [9] by M Faheem · 2015 · Cited by 276 — In this review article, we discuss the clinical manifestations of autosomal recessive primary microcephaly (MCPH), its incidence, and molecular genetics.

Note: The above information is based on search results [7], [5], and [9].