Tetrasomy 21pter→q21.2 in a male infant without typical Down’s syndrome dysmorphic features but moderate mental retardation

Down’s syndrome is caused by trisomy of chromosome 21. This invariably results in cognitive impairment, hypotonia, and characteristic phenotypic features such as flat facies, upslanting palpebral fissures, and inner epicanthal folds, and variations in digits and the ridge formation on hands and feet. Furthermore, trisomy 21 is a risk factor for congenital heart disease, Hirschsprung’s disease, and many other developmental abnormalities.1 The physical phenotype of Down’s syndrome has often been attributed to an imbalance of the region comprising bands in chromosome region q22.1–q22.3.1 However, imbalance of other regions on chromosome 21 may also contribute to the phenotype. A “phenotypic map” established from cell lines from patients with partial trisomy 21 suggested that Down’s syndrome is a contiguous gene syndrome. These results argued against a single chromosomal region responsible for most of the Down’s syndrome phenotypic features.2 However, it still remains unknown how the inheritance of three copies of chromosome 21 produces this broad spectrum of problems and which genes on chromosome 21 play a key role in the various symptoms characterising the syndrome. Patients with over-representation of defined regions on chromosome 21 may help explain the pathogenetic mechanisms in Down’s syndrome.2 Patients with partial chromosome 21 imbalance are rare. A large number of partial chromosome 21 trisomies result from unbalanced translocations3 and are often accompanied by deletions of other regions in the genome. Such deletions undoubtedly contribute to the phenotypic changes in addition to the partial trisomy 21. Particularly rare cases are complete or partial tetrasomy 21 that usually involve no other chromosome material. To our knowledge, complete or partial tetrasomy 21 without mosaicism has been reported in only five liveborn infants.4–8 Four of these five infants showed classical dysmorphic signs of Down’s syndrome4–6,8 (table 1). In the case described …