Chromosomal deletion syndromes result from loss of parts of chromosomes. They may cause severe congenital anomalies and significant intellectual and physical disability. Specific chromosomal deletion syndromes are less likely to be suspected prenatally but may be incidentally discovered at that time if karyotyping is done for other reasons. Postnatal diagnosis is suspected by clinical appearance and is confirmed by karyotyping, if the deletion is relatively large, or by other cytogenetic techniques such as fluorescent in situ hybridization or microarray analysis.
(See also Overview of Chromosomal Anomalies.)
Chromosomal deletion syndromes typically involve larger deletions that are usually visible on karyotyping. Syndromes involving smaller deletions (and additions) that affect one or more contiguous genes on a chromosome and are not visible on karyotyping are considered microdeletion and duplication syndromes. (See also Next-generation sequencing technologies.)
5p- syndrome (5p minus syndrome or cri-du-chat syndrome)
Deletion of the end of the short arm of chromosome 5 (5p minus, usually paternal) is characterized by a high-pitched, mewing cry, closely resembling the cry of a kitten, which is typically heard in the immediate neonatal period, lasts several weeks, and then disappears. However, not all affected neonates have this unusual cry. Affected neonates are hypotonic and have low birth weight, microcephaly, a round face with wide-set eyes, downward slanting of the palpebral fissures (with or without epicanthal folds), strabismus, and a broad-based nose. The ears are low-set, abnormally shaped, and frequently have narrow external auditory canals and preauricular tags. Syndactyly, hypertelorism, and cardiac anomalies occur often. Mental and physical development is markedly retarded. Many affected children survive into adulthood but have significant disability.
4p- syndrome (4p minus syndrome or Wolf-Hirschhorn syndrome)
Deletion of the short arm of chromosome 4 (4p) results in variable intellectual disability; individuals with larger deletions are usually more severely affected. Manifestations also may include epilepsy, a broad or beaked nose, midline scalp defects, ptosis and colobomas, cleft palate, delayed bone development, and, in boys, hypospadias and cryptorchidism. Some patients with Wolf-Hirschhorn syndrome also have immune deficiency. Many affected children die during infancy; those who survive into their 20s often have severe disability.
These deletions may be visible on karyotyping but are also sometimes small and submicroscopic and may occur at either telomere (the end of a chromosome). Phenotypic changes may be subtle. Subtelomeric deletions may be associated with nonspecific intellectual disability and mildly dysmorphic features as well as multiple congenital anomalies.