Two distinctive classic genetic syndromes, 22q11.2 deletion syndrome and Angelman syndrome, occurring within the same family.
We document a sib pair born to a mother with a reciprocal translocation, t(15;22)(q13;q11.2): the daughter had the Angelman syndrome phenotype associated with a maternally derived 15q deletion, and the son had a phenotype associated with a 22q deletion. Adjacent two-type segregation during gametogenesis in the mother can account for the unbalanced karyotypes of the siblings. From a tetravalent chromatid formed by normal chromosome 15, derivative chromosome 15, normal chromosome 22, and derivative chromosome 22, the daughter inherited chromosome 22 and derivative chromosome 22 and the son inherited chromosome 15 and derivative chromosome 15. The family is unique in that two distinctive genetic syndromes, 22q11.2 deletion syndrome and Angelman syndrome, occurred within the same family. The family is also elucidative from an educational standpoint in that major concepts of non-Mendelian inheritance (microdeletion, genomic imprinting, and reciprocal translocation) need to be considered to appreciate the inheritance pattern. Furthermore, the family illustrates the importance of cryptic rearrangements at the most proximal end of acrocentric chromosomes in the evaluation of siblings with multiple congenital anomaly-mental retardation phenotypes that are dissimilar among affected siblings. The situation is analogous to parental balanced translocation between the most "distal" segments of a chromosome, that is, the subtelomere region, a recently appreciated cause of familial recurrence of multiple congenital anomaly-mental retardation phenotype with a normal G-banding karyotype. We suggest that cryptic rearrangements at the most proximal end, analogous to those at the most distal end, should be considered as an appreciable cause of recurrent multiple congenital anomaly-mental retardation phenotype.
Kosaki
Rika
R
Department of Clinical Genetics and Molecular Medicine, National Center for Child Health and Development, Tokyo, Japan.
Migita
Ohsuke
O
Takahashi
Takao
T
Kosaki
Kenjiro
K
D000015:Abnormalities, Multiple / Q000235:genetics; D017204:Angelman Syndrome / Q000235:genetics*; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004062:DiGeorge Syndrome / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D007621:Karyotyping; D008297:Male; D010641:Phenotype; D013577:Syndrome; D014178:Translocation, Genetic