NFIA-related disorder

NFIA-related disorder, also known as 1p31p32 microdeletion syndrome or brain malformations with or without urinary tract defects, is a rare genetic disorder caused by mutations in the NFIA gene.

Clinical Characteristics:

• Central nervous system abnormalities (most commonly corpus callosum abnormalities)
• Urinary tract defects (unilateral or bilateral)
• Dysmorphic features
• Macrocephaly (enlarged head size)

Genetic Basis:

• The NFIA gene is located at 1p31.3 and encodes the transcription factor NFIA.
• Mutations in the NFIA gene can result in haploinsufficiency, leading to an NFIA-related disorder.
• Deletions or point mutations in the NFIA gene are responsible for this condition.

Prevalence:

• NFIA-related disorder is a rare genetic disorder with only 20 reported cases in the literature.
• The majority of these cases were caused by smaller intragenic deletions or point mutations, while others resulted from multigenic microdeletions.

Inheritance Pattern:

• NFIA-related disorder can be inherited in an autosomal dominant pattern.
• However, most cases are sporadic and not inherited.

Symptoms:

• The symptoms of NFIA-related disorder vary depending on the severity of the mutation and the presence of other genetic abnormalities.
• Common symptoms include macrocephaly, craniofacial abnormalities, and urinary tract defects.

Diagnosis:

• Diagnosis is typically made through whole exome sequencing or targeted gene analysis.
• Careful observation of specific dysmorphisms, such as macrocephaly and craniofacial abnormalities, can also suggest NFIA haploinsufficiency.

References:

[1] [2] [3-10]

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

NFIA-related disorder, also known as NFIA haploinsufficiency syndrome, is a rare genetic condition characterized by various signs and symptoms affecting the central nervous system (CNS) and other bodily systems.

Common Signs and Symptoms:

• Central Nervous System Abnormalities: The most common CNS abnormalities associated with NFIA-related disorder include:
  • Macrocephaly (larger-than-normal head size)
  • Ventriculomegaly (enlarged ventricles in the brain)
  • Hypotonia (low muscle tone)
  • Seizures
  • Developmental delay and/or cognitive impairment
• Urinary Tract Defects: Many individuals with NFIA-related disorder also experience urinary tract defects, such as hydronephrosis (swelling of the kidney due to a blockage) and renal cysts.
• Dysmorphic Features: Some people may exhibit mildly dysmorphic facial features.

Other Associated Features:

• Corpus callosum abnormalities
• Hypoplasia (underdevelopment) of certain brain structures
• Intellectual disability

These signs and symptoms can vary significantly in severity and presentation among individuals with NFIA-related disorder. The condition is often diagnosed through a combination of clinical evaluation, genetic testing, and imaging studies.

References:

[2] Additional features include macrocephaly, seizures, developmental delay, ventriculomegaly, and hypotonia (5, 6). [3] NFIA-related disorder comprises central nervous system abnormalities (most commonly abnormalities of the corpus callosum) with or without urinary tract defects, [6] Additional features include macrocephaly, seizures, developmental delay and/or cognitive impairment, nonspecific dysmorphic features, ventriculomegaly, and ... [7] Hydronephrosis and renal cysts are the most common clinical signs ... NFIA haploinsufficiency is associated with a CNS malformation syndrome and ... [8] Haploinsufficiency of the NFIA gene causes NFIA-related disorder, which includes brain abnormalities and intellectual disability, with or ...

Diagnosing NFIA-related Disorder: A Comprehensive Overview

NFIA-related disorder, also known as NFIA haploinsufficiency, can be challenging to diagnose due to its wide-ranging manifestations and the variety of symptoms it presents. However, with careful observation and a combination of diagnostic tests, healthcare professionals can establish an accurate diagnosis.

Diagnostic Clues through Observation

Careful observation of specific dysmorphisms, including macrocephaly (larger-than-normal head size) and craniofacial abnormalities, can be indicative of NFIA haploinsufficiency [3]. These physical characteristics may suggest the presence of a genetic disorder, prompting further diagnostic testing.

Genetic Testing: A Key Diagnostic Tool

Molecular genetic testing approaches can include:

• Chromosomal microarray analysis (CMA)
• Multigene panel
• Exome or genome sequencing

These tests can help identify pathogenic variants in the NFIA gene, deletions of the 1p31.3 region that includes part or all of NFIA, or chromosome translocations/rearrangements with a 1p31 [10][11]. The detection of one of these genetic abnormalities can establish the diagnosis of NFIA-related disorder.

Instrumental Tests: Additional Diagnostic Clues

Instrumental tests such as MRI and kidney/urinary tract ultrasound can provide further diagnostic clues, while genetic testing can confirm the diagnosis [9][15]. These tests may reveal specific features associated with NFIA haploinsufficiency, supporting a diagnosis of NFIA-related disorder.

Comprehensive Genomic Testing: A More Detailed Approach

More comprehensive genomic testing, including exome sequencing and genome sequencing, may be considered when available. Such testing can provide additional information about the genetic basis of NFIA-related disorder [6][7].

In summary, diagnosing NFIA-related disorder requires a combination of careful observation, genetic testing, and instrumental tests. By considering these diagnostic approaches, healthcare professionals can establish an accurate diagnosis and guide appropriate management strategies for affected individuals.

References:

[3] Dini G et al. (2023) - Suspecting NFIA haploinsufficiency through specific dysmorphisms. [6] Senaratne TN (no date) - More comprehensive genomic testing for NFIA-related disorder. [7] Senaratne TN (no date) - More comprehensive genomic testing for NFIA-related disorder. [9] Bertini V et al. (2022) - Instrumental tests for diagnosing NFIA haploinsufficiency. [10] Paschell P et al. (2023) - Diagnostic criteria for NFIA-related disorder. [11] Paschell P et al. (2023) - Diagnostic criteria for NFIA-related disorder. [13] Politi A Revah et al. (2017) - Loss-of-function variants in NFIA and 1p32-p31 deletion syndrome. [15] Politi A Revah et al. (no date) - Instrumental tests for diagnosing NFIA haploinsufficiency.

Treatment Options for NFIA-related Disorder

NFIA-related disorder, also known as corpus callosum hypoplasia, is a rare genetic condition characterized by the underdevelopment of the corpus callosum, macrocephaly, and developmental delay. While there is no specific treatment for

NFIA-related disorder has a differential diagnosis that includes several conditions that can present with similar symptoms. Some of these conditions are:

• Chromosome 1p32-p31 deletion syndrome involving the Nuclear factor I/A (NFIA) gene, which is characterized by corpus callosum hypoplasia or defects [7][8].
• Haploinsufficiency of the NFIA gene causes NFIA-related disorder, which includes brain abnormalities and intellectual disability, with or without urinary tract defects [10].
• Macrocephaly, craniofacial, and first-finger anomalies are also associated with NFIA haploinsufficiency [9].

It's worth noting that NFIA-related disorder is a rare condition, having been described in only 13 families representing 20 affected individuals [6]. A careful observation of specific dysmorphisms, including macrocephaly and craniofacial abnormalities, can be used to suspect NFIA haploinsufficiency [3].

In terms of differential diagnosis, it's essential to consider the characteristic MRI findings ("molar tooth sign") and eye abnormalities associated with NFIA-related disorder [2]. A thorough evaluation of these symptoms, along with a review of the patient's medical history and physical examination, can help differentiate NFIA-related disorder from other conditions.

References: [1] TN Senaratne · 2019 · Cited by 10 [2] TN Senaratne · 2019 · Cited by 10 [3] G Dini · 2023 · Cited by 2 [4] P Paschell · 2024 [5] TN Senaratne [6] NFIA-related disorder is rare, having been described in only 13 families representing 20 affected individuals. [7] by Y Negishi · 2015 · Cited by 33 — Chromosome 1p32-p31 deletion syndrome involving the Nuclear factor I/A (NFIA) gene is characterized by corpus callosum hypoplasia or defects ... [8] by TN Senaratne · 2019 · Cited by 10 — NFIA-related disorder comprises central nervous system abnormalities (most commonly abnormalities of the corpus callosum) with or without urinary tract defects, ... [9] by V Bertini · 2022 · Cited by 5 — NFIA haploinsufficiency can be suspected by a careful observation of the dysmorphisms (macrocephaly, craniofacial, and first-finger anomalies), ... [10] Haploinsufficiency of the NFIA gene causes NFIA-related disorder, which includes brain abnormalities and intellectual disability, with or without urinary ...