Pt

A 6-month-old infant presenting with a small corpus callosum and insatiable appetite raises concern for a syndromic or neurodevelopmental condition. Here’s a differential diagnosis (DDx) to consider:

1. Prader-Willi Syndrome (PWS)

• Key features: Hypotonia in infancy, poor feeding early on → followed by hyperphagia (insatiable appetite), developmental delay, small hands/feet, almond-shaped eyes.
• Corpus callosum: May be hypoplastic or abnormal in some cases.
• Cause: Loss of paternal 15q11-q13 (either deletion or maternal uniparental disomy).
• Testing: DNA methylation analysis for 15q11-q13 region.

2. Septo-Optic Dysplasia (SOD)

• Features: Hypoplasia of corpus callosum, optic nerve hypoplasia, pituitary hormone deficiencies.
• Appetite: Can have hypothalamic dysfunction leading to abnormal feeding behavior.
• Imaging: MRI shows midline brain anomalies.
• Ophthalmologic and endocrine evaluation is key.

3. Congenital Hypothalamic Syndromes / Hypothalamic Hamartoma

• Hypothalamic dysregulation can lead to hyperphagia, temperature instability, and behavioral issues.
• May be associated with corpus callosum abnormalities.

4. Genetic Syndromes

• Several genetic syndromes can present with corpus callosum agenesis/hypoplasia and feeding abnormalities:
  
• Pitt-Hopkins Syndrome
• Cohen Syndrome
• Smith-Lemli-Opitz Syndrome
• Pallister-Killian Syndrome
• 
  
• Usually accompanied by dysmorphic features or developmental delays.

5. Metabolic/Neurodegenerative Disorders

• Though less common, some disorders (e.g., leukodystrophies) can present with structural brain anomalies and abnormal appetite as part of broader neuroregression.

Workup recommendations:

• Brain MRI (already likely done)
• Genetic testing: Chromosomal microarray, Prader-Willi methylation analysis, whole exome sequencing if needed
• Endocrine panel: Especially to rule out hypothalamic-pituitary axis dysfunction
• Ophthalmology eval: For optic nerve hypoplasia
• Developmental assessment

Would you like a structured diagnostic flowchart or lab/imaging guide for next steps?