X-Linked Lissencephaly With Absent Corpus Callosum and Abnormal Genitalia: An Evolving Multisystem Syndrome With
David Coman1,2,3, Tom Fullston4,5, Cheryl Shoubridge4
1Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia.
Insights
X-linked lissencephaly with abnormal genitalia is a rare syndrome. A novel ARX gene mutation was identified in an infant with severe intestinal and central nervous system issues, impacting enteroendocrine system development.
Area of Science:
- Genetics
- Developmental Biology
- Pediatric Medicine
Background:
- X-linked lissencephaly with abnormal genitalia is a rare and severe genetic disorder.
- The syndrome presents with significant central nervous system abnormalities and other multisystemic features.
- Intestinal manifestations can be life-limiting, posing critical challenges in patient management.
Purpose of the Study:
- To report a case of X-linked lissencephaly with abnormal genitalia.
- To detail the multisystemic phenotype, emphasizing severe intestinal complications.
- To identify the molecular genetic basis of the disorder in this patient.
Main Methods:
- Clinical case presentation and detailed phenotypic analysis.
- Histological examination of affected tissues.
- Molecular genetic analysis, including gene sequencing to identify mutations.
Main Results:
- The infant exhibited severe chronic diarrhea, failure to thrive, dehydration, and electrolyte imbalances.
- Additional findings included megacolon, colitis, pancreatic insufficiency, and endocrine dysfunctions (hypothyroidism, hypophosphatasia).
- A novel mutation in the aristaless-related homeobox (ARX) gene (c.1136G>T/p.R379L) was identified.
Conclusions:
- This case highlights the critical role of the ARX gene in the development of the enteroendocrine system.
- The study expands the understanding of the multisystemic nature of X-linked lissencephaly with abnormal genitalia.
- Early identification of ARX mutations is crucial for understanding and managing this devastating syndrome.
Abstract:
X-linked lissencephaly with abnormal genitalia is a rare and devastating syndrome. The authors present an infant with a multisystem phenotype where the intestinal manifestations were as life limiting as the central nervous system features. Severe chronic diarrhea resulted in failure to thrive, dehydration, electrolyte derangements, long-term hospitalization, and prompted transition to palliative care. Other multisystem manifestations included megacolon, colitis, pancreatic insufficiency hypothalamic dysfunction, hypothyroidism, and hypophosphatasia. A novel aristaless-related homeobox gene mutation, c.1136G>T/p.R379L, was identified. This case contributes to the clinical, histological, and molecular understanding of the multisystem nature of this disorder, especially the role of ARX in the development of the enteroendocrine system.
Related Concept Videos
01:43Sex-linked Disorders
01:33Pleiotropy
02:30Genomic Imprinting and Inheritance
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
01:19Autism Spectrum Disorder
These core symptoms manifest differently among individuals, ranging from mild to severe. The disorder's complexity extends beyond its clinical presentation, encompassing a diverse range of biological, cognitive, and sociocultural influences.
01:17Chronic Bowel Disorders: Introduction
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...
01:22Lysosomal Hydrolases