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Cleft palate and complex chromosome rearrangements
B G Kousseff1, P Papenhausen, R L Neu
1Department of Pediatrics, University of South Florida, Tampa 33612.
Insights
Congenital complex chromosome rearrangements (CCR) can cause cleft lip and palate in children. Doctors should consider CCR in patients with cleft palate and other anomalies for accurate diagnosis and genetic counseling.
Area of Science:
- Genetics
- Developmental Biology
- Clinical Genetics
Background:
- Congenital anomalies can arise from complex chromosomal abnormalities.
- De novo congenital complex chromosome rearrangements (CCR) involve multiple chromosome breaks and rearrangements.
Observation:
- Two unrelated children with de novo CCR and over four breaks presented with cleft lip and palate.
- Patient 1 had unilateral cleft palate, ectrodactyly, choanal atresia, and six breakpoints with multiple chromosomal aberrations.
- Patient 2 exhibited bilateral cleft lip and palate, growth retardation, and six breakpoints with chromosomal deletions, translocations, and an inversion.
Findings:
- Both patients had de novo CCR involving multiple chromosomes, suggesting a gametic "catastrophe" event.
- Parental karyotypes were normal, indicating the rearrangements were new in the children.
- The identified chromosomal aberrations were stable without evidence of persistent instability.
Implications:
- Cleft palate, especially with other anomalies, warrants consideration of CCR in clinical genetic evaluation.
- Accurate cytogenetic diagnosis is crucial for prognosis, management, and genetic counseling.
- Understanding CCR is essential for assessing lifespan, quality of life, and reproductive options for affected families.
Abstract:
Two of three unrelated children with de novo congenital complex chromosome rearrangements (CCR) with more than four chromosome breaks had cleft lip and palate as one of several congenital anomalies. In patient 1, unilateral complete cleft of the primary and secondary palates accompanied severe ectrodactyly, bilateral posterior choanal atresia and several minor congenital anomalies. Karyotypes of peripheral lymphocytes and skin fibroblasts showed five derivative chromosomes with six break points. There were two translocations, t(2;5), t(3;11) and an interstitial deletion, del(13)(q12q14). Patient 2 had a bilateral complete cleft of the lip and palate, in addition to slow pre- and postnatal growth and minor congenital anomalies. Peripheral lymphocytes and palatal mucosa fibroblasts karyotypes showed five derivative chromosomes with six break points. A partial deletion of 10p, two translocations, t(2;3), t(7;18) and an inversion of the derivative chromosome 2 were present. In both patients, a "major catastrophe" of unknown etiology in one of the parental gametes appeared to be the event leading to the stable CCR without evidence of persistent chromosome instability. All four parents had normal karyotypes. The presence of palatal clefts in these patients indicates that dysmorphologists and pediatricians have to consider CCR whenever taking care of a patient with cleft palate, particularly if additional anomalies, no matter how subtle, are present. The detection and interpretation of the latter anomalies are essential for the diagnosis and management of these patients. Accurate cytogenetic diagnosis determines the short- and long-term prognosis and facilitates genetic counseling in regard to life-span, quality of life and reproductive plans of patients and parents.