Genomic coordinate: (human 10:102,230,189 PITX3) & (mouse 19:46,124,124 Pitx3).
Cytoband: (human 10q24.32 PITX3) & (mouse 19qC3 Pitx3).
Here I present: “Anterior Segment Mesenchymal Dysgenesis“, Victor McKusick, Mendelian Inheritance in Man’, 1966. (PITX3) 眼前段間質發育不全。icd10=Q13.8
INTRODUCTION.
Anterior segment mesenchymal dysgenesis (ASMD) is a group of congenital developmental disorders of the eye’s anterior segment (cornea, iris, trabecular meshwork, and anterior chamber angle). It results from abnormal migration, differentiation, or survival of neural crest–derived mesenchymal cells during early embryogenesis (≈ weeks 4–7).
Key Ocular Structures Affected.
Cornea – endothelium, Descemet membrane, stroma.
Iris – stroma, pupil formation.
Anterior chamber angle – trabecular meshwork, Schlemm canal.
Lens position (secondary effects).
Major Clinical Entities within ASMD.
1. Axenfeld Anomaly.
Prominent, anteriorly displaced Schwalbe line (posterior embryotoxon)
Iris strands attached to cornea
Often asymptomatic initially
2. Rieger Anomaly.
Axenfeld features plus iris abnormalities
Iris hypoplasia
Corectopia (displaced pupil)
Polycoria (multiple pupils)
3. Axenfeld–Rieger Syndrome.
Ocular findings plus systemic abnormalities
Systemic features:
Dental anomalies (hypodontia, microdontia)
Craniofacial abnormalities (maxillary hypoplasia)
Umbilical defects
High risk of glaucoma (≈50%)
4. Peters Anomaly.
Central corneal opacity (leukoma)
Absence of Descemet membrane and corneal endothelium centrally
Iris–cornea or lens–cornea adhesions
Can be unilateral or bilateral
5. Aniridia
Partial or near-total absence of iris
Often associated with PAX6 mutation
High risk of glaucoma, cataract, keratopathy
Genetics
Common genes implicated:
PITX2 – Axenfeld–Rieger syndrome
FOXC1 – Axenfeld–Rieger spectrum
PAX6 – Aniridia
CYP1B1 – congenital glaucoma overlap
B3GLCT – Peters plus syndrome
PITX3-related Differential Diagnosis.
PITX3-related ASMD must be distinguished from:
PAX6 – Aniridia.
PITX2 – Axenfeld–Rieger syndrome.
FOXC1 – Axenfeld–Rieger spectrum
CYP1B1 – Primary congenital glaucoma.
LMX1B – Nail–patella syndrome.
Inheritance patterns:
Autosomal dominant (most common).
Autosomal recessive (some Peters anomaly forms)
Major Complication:
Glaucoma
Occurs in 30–70% of patients depending on subtype
Due to malformed trabecular meshwork
May present in childhood or adulthood
There is evidence that anterior segment mesenchymal dysgenesis can be caused by mutation in the pituitary homeobox-3 gene (PITX3) encoded on genomic coordinate 10:102,230,189 and cytoband 10q24.32 in humans.
