AJNR Case Collection

Background:
Mutations or deletions involving the NFIA gene are linked to a range of brain malformations and developmental anomalies. These include significant structural abnormalities in the central nervous system, such as hypogenesis of the corpus callosum, optic nerve anomalies, and pituitary hypoplasia.

Clinical Presentation:
Patients commonly present with global developmental delay, impaired speech and language, and various craniofacial features. Ocular manifestations, including strabismus and the appearance of optic disc congestion, are also reported. Endocrine dysfunction may be associated with pituitary hypoplasia.

Key Diagnostic Features:
• Corpus callosum: Hypogenesis is a common finding in NFIA mutation cases, possibly manifesting as absence of key structures such as the splenium and the rostrum, as observed in this patient.
• Optic nerves: Tortuosity of the optic nerves and ectasia of the optic nerve sheaths are present in this case. Additionally, optic disc congestion, a feature previously reported in NFIA-associated disorders, was also noted.
• Pituitary gland: Reduced thickness of the anterior pituitary has been documented in the literature and is evident in this patient.

Differential Diagnosis:
• Septo-optic dysplasia: Characterized by any combination of optic nerve hypoplasia, endocrine abnormalities (commonly ectopic neurohypophysis), absence of the septum pellucidum, and malformations of cortical development
• Aicardi syndrome: Typically presents with the triad of infantile spasms, corpus callosum dysgenesis, and distinctive chorioretinal lacunae, occurring in females
• Mowat-Wilson syndrome: Recognized by corpus callosum hypogenesis/agenesis, distinctive facial dysmorphism, and congenital malformations such as Hirschsprung disease and genitourinary anomalies
• Axenfeld-Rieger syndrome: Characterized by anterior segment dysgenesis of the eye, distinctive craniofacial features, and, in some cases, pituitary abnormalities

Management:
• Developmental interventions: Early intervention with speech, occupational, and physical therapy is crucial.
• Ophthalmologic follow-up: Regular monitoring for strabismus and optic nerve changes
• Endocrine surveillance: Routine evaluation and management of potential pituitary insufficiencies
• Genetic counseling: Advised for affected families to discuss genetic inheritance and future risks