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Ring chromosome 4 and Wolf-Hirschhorn syndrome (WHS) in a child with multiple anomalies

Sevim Balci1, Ozlem Engiz, Dilek Aktaş

  • 1Department of Clinical Genetics, Hacettepe University Faculty of Medicine, Ihsan Doğramaci Children's Hospital, Ankara, Turkey. sbalci@hacettepe.edu.tr

American Journal of Medical Genetics. Part A
|February 14, 2006
PubMed

Insights

A rare ring chromosome 4 in a male infant caused multiple congenital anomalies, including facial clefts and microcephaly. This case highlights the complex genetic basis of Wolf-Hirschhorn syndrome (WHS) deletions.

Area of Science:

  • Genetics
  • Developmental Biology
  • Clinical Medicine

Background:

  • Ring chromosome 4 (r(4)) is a rare chromosomal abnormality.
  • Wolf-Hirschhorn syndrome (WHS) is associated with deletions in the 4p16.3 region.
  • Multiple congenital anomalies (MCAs) can arise from complex chromosomal rearrangements.

Observation:

  • A 16-month-old male presented with MCAs including unilateral cleft lip and palate, iris coloboma, microcephaly, midgut malrotation, hypospadias, and double urethral orifices.
  • Karyotype revealed 46,XY,r(4)(p16.3q35) de novo.
  • FISH and chromosomal microarray confirmed deletions in the subtelomeric 4p and 4q regions, including the WHS critical region.

Findings:

  • The patient's r(4) involved deletions of the 4p subtelomeric region, 4q subtelomeric region, and the WHS critical region.
  • Cranial MRI demonstrated hypoplastic corpus callosum, delayed myelination, and frontal and occipital lobe atrophies.
  • Parental chromosomal analyses were normal, indicating a de novo event.

Implications:

  • This case expands the understanding of phenotypic variability in ring chromosome 4.
  • It underscores the importance of comprehensive genetic analysis for diagnosing complex congenital anomalies.
  • Comparing this patient's phenotype with 16 previously reported r(4) cases provides insights into genotype-phenotype correlations.

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