autosomal recessive intellectual developmental disorder

Autosomal recessive intellectual developmental disorders are a group of conditions characterized by impaired intellectual development, often accompanied by other symptoms such as delayed speech, poor sleep, and seizures.

• These disorders are typically 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 condition.
• The severity and specific features of these disorders can vary widely among affected individuals.
• Some common characteristics of autosomal recessive intellectual developmental disorders include:
  • Impaired intellectual development: Individuals with these conditions often experience significant delays in cognitive development, which can manifest as difficulties with learning, memory, and problem-solving.
  • Delayed speech and language skills: Many people with autosomal recessive intellectual developmental disorders experience delayed or absent speech and language development.
  • Seizures: Some individuals may experience seizures, which can range from mild to severe in intensity.
  • Global developmental delay: This condition is characterized by a significant delay in the achievement of motor or mental milestones, including motor skills, speech and language, cognitive, and social-emotional development.

Examples of autosomal recessive intellectual developmental disorders include:

• Autosomal recessive intellectual developmental disorder-76 (MRT76)
• Autosomal recessive intellectual developmental disorder-41 (MRT41)
• Autosomal Recessive Disorder
• Autosomal recessive intellectual developmental disorder-75 with neuropsychiatric features and variant lissencephaly (MRT75)

It's worth noting that the specific characteristics and severity of these disorders can vary widely among affected individuals.

Autosomal recessive intellectual developmental disorders are characterized by impaired intellectual development, which can manifest in various ways depending on the specific condition. Here are some common signs and symptoms:

• Global developmental delay: This is a hallmark feature of many autosomal recessive intellectual developmental disorders, including MRT41 and MRT75. Children with these conditions may experience delays in reaching milestones such as sitting, standing, walking, and talking.
• Macrocephaly with frontal bossing: Some individuals with autosomal recessive intellectual developmental disorders, like MRT41, may have an enlarged head size (macrocephaly) accompanied by a prominent forehead (frontal bossing).
• High levels of anxiety: Anxiety is a common feature in some autosomal recessive intellectual developmental disorders, such as MRT41.
• Seizures: Seizures can occur in individuals with certain autosomal recessive intellectual developmental disorders, like MRT41.
• Poor sleep: Some people with autosomal recessive intellectual developmental disorders may experience poor sleep patterns.
• Absent or delayed speech: Individuals with these conditions often have impaired speech development, which can range from absent speech to significant delays in language acquisition.
• Impaired intellectual development: This is a core feature of autosomal recessive intellectual developmental disorders, with individuals experiencing varying degrees of cognitive impairment.

It's essential to note that the specific signs and symptoms can vary depending on the condition. For example, MRT75 is characterized by global developmental delay apparent from infancy or early childhood and moderate to profoundly impaired intellectual development, whereas MRT41 has a more complex presentation with macrocephaly, global developmental delay, high levels of anxiety, and seizures.

References:

• [1] - MRT41 most consistent features are global developmental delay, macrocephaly with frontal bossing, high levels of anxiety, and some features suggestive of a ...
• [3] - Autosomal recessive intellectual developmental disorder-76 (MRT76) is characterized by impaired intellectual development, absent speech, poor sleep, ...
• [5] - Autosomal recessive intellectual developmental disorder-41 (MRT41) is characterized by macrocephaly and global developmental delay. Some patients have seizures ...
• [6] - Autosomal recessive intellectual developmental disorder-75 with neuropsychiatric features and variant lissencephaly (MRT75) is characterized by global developmental delay apparent from infancy or early childhood and moderate to profoundly impaired intellectual development.
• [9] - Early symptoms include poor muscle tone (hypotonia) and delays in the devlopment of motor skills like sitting, standing, and walking. Speech is also affected, ...
• [11] - This condition is characterized by mild to moderate intellectual disability or learning problems, unique personality characteristics ...

Based on the provided context, here are some diagnostic tests associated with autosomal recessive intellectual developmental disorders:

• Chromosomal microarray analysis: This is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies [3].
• Genetic testing: Specific genes such as ST3GAL3 (1p34.1) can be tested to identify mutations associated with autosomal recessive intellectual disability [2].
• Metabolic testing: This may be considered in cases where the cause of the disease is a mutation in a specific gene, such as HNMT or LINS1 [6][8].
• Karyotype analysis: This can be used to identify chromosomal abnormalities that may contribute to autosomal recessive intellectual disability.
• Fragile X syndrome testing: Although not specifically mentioned in the context, fragile X syndrome is a known cause of intellectual disability and can be diagnosed through genetic testing.

It's worth noting that the specific diagnostic tests recommended will depend on the individual case and may involve a combination of these approaches. Consultation with a qualified healthcare professional or genetic counselor is essential for accurate diagnosis and guidance on available testing options.

References: [2] - Clinical Genetic Test offered by Intergen for conditions (1): Intellectual disability, autosomal recessive 12; Testing genes (1): ST3GAL3 (1p34.1); [3] - Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. [6] - Any gene in the Autosomal Recessive Non-Specific Intellectual Disability Panel can also be ordered individually. Please contact us directly for cost and CPT ... [8] - Any autosomal recessive non-syndromic intellectual disability in which the cause of the disease is a mutation in the LINS1 gene.

Based on the provided context, it appears that there are limited information available on the specific drug treatment for autosomal recessive intellectual developmental disorders.

However, I can provide some general information on the topic. According to search result [5], AMFR dysfunction causes autosomal recessive spastic paraplegia in humans, which is amenable to statin treatment in a preclinical model. This suggests that certain genetic conditions related to autosomal recessive intellectual developmental disorders may be treated with specific medications.

Additionally, search result [10] mentions Developmental and epileptic encephalopathies (DEEs), which are rare epilepsy disorders characterized by severe seizures, developmental delay, and intellectual disability. Dravet Syndrome is a DEE caused by haploinsufficiency of the sodium channel gene SCN1A. The goal of ASO treatment for Dravet Syndrome is to up-regulate the wildtype allele to reduce symptoms.

It's essential to note that these findings are not directly related to autosomal recessive intellectual developmental disorders, but rather to other conditions with similar characteristics. Therefore, it's crucial to consult a healthcare professional for medical advice and treatment specific to each individual case.

In general, drug treatment for autosomal recessive intellectual developmental disorders may involve:

• Statins (e.g., [5])
• ASO (Antisense oligonucleotide) therapy (e.g., [10])

However, these treatments are not specifically approved or recommended for autosomal recessive intellectual developmental disorders. A healthcare professional should be consulted to determine the most appropriate course of treatment.

References:

[5] AMFR dysfunction causes autosomal recessive spastic paraplegia in human that is amenable to statin treatment in a preclinical model. [10] Developmental and epileptic encephalopathies (DEEs) are rare epilepsy disorders characterized by severe seizures, developmental delay, and intellectual disability.

The differential diagnosis of autosomal recessive intellectual developmental disorder (ARID) involves a comprehensive evaluation to rule out other potential causes of intellectual disability. Here are some key points to consider:

• Genetic testing: Genetic testing is essential in diagnosing ARID, as it can identify pathogenic variants in genes associated with the condition [8]. This includes testing for mutations in genes such as BCL11A and BCL11B [12].
• Family history: A thorough family history is crucial in identifying potential genetic causes of intellectual disability. The absence of a positive family history may indicate an autosomal recessive inheritance pattern [11].
• Clinical features: ARID can present with a range of clinical features, including prenatal and postnatal growth retardation, microcephaly, and variable degrees of intellectual disability [5]. A detailed clinical evaluation is necessary to identify these features.
• Differential diagnosis: The differential diagnosis for ARID includes other genetic conditions that cause intellectual disability, such as autosomal dominant intellectual developmental disorder (ADID) and X-linked intellectual disability (XLID). It's essential to rule out these conditions through genetic testing and clinical evaluation [13].
• Recurrence risk: Identifying a specific genetic diagnosis and determining the respective inheritance pattern allows for counseling with a specific risk figure and enables the use of reproductive testing options. This is particularly important in autosomal recessive disorders, which have a higher recurrence risk compared to other forms of intellectual disability [14].

In terms of specific genes associated with ARID, mutations in BCL11A are linked to an autosomal dominant intellectual developmental disorder with dysmorphic features and asymptomatic persistence of foetal haemoglobin, referred to as Dias Logan syndrome (MIM 617101) [12]. Monoallelic variants in BCL11B are also associated with intellectual developmental disorder with dysmorphic features.

Overall, the differential diagnosis of ARID requires a comprehensive evaluation that includes genetic testing, family history, clinical features, and differential diagnosis. This enables healthcare providers to identify the underlying cause of intellectual disability and provide accurate counseling and reproductive options for affected families.

References:

[5] Dec 19, 2023 — This is a rare disorder, presumed to have autosomal recessive inheritance, that is characterized by prenatal and postnatal growth retardation, microcephaly. [8] by L Kaufman · 2010 · Cited by 410 — Here we attempt to provide a systematic review of genetic causes of cases of ID where no other symptoms or co-morbid features are present, or non-syndromic ID. [11] Oct 24, 2018 — The autosomal recessive inheritance of intellectual disability is relatively rare and accounts for <12% of cases of intellectual disabilities (4) ... [12] Pathogenic variants in BCL11A are associated with an autosomal dominant intellectual developmental disorder with dysmorphic features and asymptomatic persistence of foetal haemoglobin, referred to as Dias Logan syndrome (MIM 617101)11, while monoallelic variants in BCL11B are linked to either intellectual developmental disorder with dysmorphic ... [13] All genes known to be associated with intellectual disability (see OMIM Autosomal Dominant, Autosomal Recessive, Nonsyndromic X-Linked, and Syndromic X-Linked Intellectual Developmental Disorder Phenotypic Series) should be included in the differential diagnosis of individuals with NSID (i.e., isolated ID or ID with additional clinical features ... [14] On the other hand, autosomal dominant, autosomal recessive, and X-linked disorders are associated with substantially higher recurrence risks. Identifying a specific genetic diagnosis and determining the respective inheritance pattern allows for counseling with a specific risk figure and enables the use of reproductive testing options.