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Kenny-Caffey syndrome is part of the CATCH 22 haploinsufficiency cluster
M A Sabry1, M Zaki, S J Abul Hassan
1Kuwait Medical Genetics Centre, Kuwait.
Insights
Kenny-Caffey syndrome, a rare genetic disorder, is linked to 22q11.2 haploinsufficiency. This microdeletion, identified in Bedouin siblings, expands the known spectrum of CATCH 22 conditions.
Area of Science:
- Genetics
- Pediatrics
- Immunology
Background:
- Kenny-Caffey syndrome is a rare autosomal recessive disorder characterized by severe growth retardation and unique bone abnormalities.
- Previous research has not established a clear genetic cause for Kenny-Caffey syndrome.
Observation:
- Four siblings from a consanguineous Bedouin family presented with Kenny-Caffey syndrome.
- Affected individuals exhibited characteristic clinical, biochemical, and radiological features, including severe growth retardation, bone abnormalities, hypocalcemia, and immune dysfunction.
- Fluorescence in situ hybridization (FISH) revealed 22q11.2 haploinsufficiency in affected siblings, inherited from their mother.
Findings:
- The study identified 22q11.2 haploinsufficiency as a genetic cause for Kenny-Caffey syndrome in this family.
- Immune abnormalities, including impaired neutrophil function and altered T and B lymphocyte populations, were noted in affected individuals.
- The findings suggest a link between Kenny-Caffey syndrome and the DiGeorge critical region.
Implications:
- This research expands the phenotypic spectrum associated with 22q11.2 microdeletions to include Kenny-Caffey syndrome.
- It provides a potential genetic basis for Kenny-Caffey syndrome, aiding in diagnosis and genetic counseling.
- Further investigation into the role of 22q11.2 genes in skeletal and immune development is warranted.
Abstract:
We report four sibs with Kenny-Caffey syndrome in a consanguineous Bedouin family. The first two died in the neonatal period while the remaining affected brother and sister had all the characteristic clinical, biochemical, and radiological abnormalities of the syndrome. These included severe pre- and postnatal growth retardation, cortical thickening of the tubular bones with medullary stenosis, eye abnormalities, facial dysmorphism, hypocalcaemia, and low levels of parathyroid hormone. The children also showed intracranial calcification, impaired neutrophil phagocytosis, increased proportion of B lymphocytes, reduced CD4 and CD8 subpopulations of T lymphocytes, and inhibited transformation in response to Candida antigen. Fluorescence in situ hybridisation (FISH) was applied to blood lymphocyte metaphase spreads from these two Bedouin sibs and their parents using probe D22S75 (Oncor), specific for the DiGeorge critical region on chromosome 22q11.2. The presence of 22q11.2 haploinsufficiency was identified in the affected sibs, which was transmitted from the phenotypically normal mother. The present report widens the spectrum of CATCH 22 microdeletion to accommodate Kenny-Caffey syndrome.