Cri-du-chat Syndrome, 5p15.2 Deletion, FISH
As an aid in the diagnosis of cri-du-chat syndrome, in conjunction with CMS / Chromosome Analysis, For Congenital Disorders, Blood
Detecting cryptic translocations involving 5p15.2 that are not demonstrated by conventional chromosome studies
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Cri-du-chat syndrome is associated with a deletion on the short arm of chromosome 5 (5p-). The syndrome can be suspected in infants with a plaintive, mewing cry, low birth weight, and failure to thrive. The weak kittenlike cry that gives name to the syndrome is at least partly due to anatomic abnormalities of the larynx and although the cry changes with time, it does not become normal. Facial features include microcephaly, round face, low-set ears, strabismus, hypertelorism (wide-set eyes), and epicanthus (a vertical fold of skin on either side of the nose). The hands and feet are small, and the hands often have a single crease extending across the palm (simian crease). With age, premature gray hair, dental malocclusion, inguinal hernia, distasis recti, (a separation of the left and right side of the rectus abdominis muscle), and scoliosis are common. Affected individualsâ€™ intelligence varies widely from mild-to-severe mental retardation.
FISH studies are highly specific and do not exclude other chromosome abnormalities. We recommend that patients suspected of having cri-du-chat syndrome also have conventional chromosome studies (CMS / Chromosomes Analysis, for Congenital Disorders, Blood) performed to rule out other chromosome abnormalities or translocations.
An interpretive report will be provided.
Any individual with a normal signal pattern (2 signals) in each metaphase is considered negative for a deletion in the region tested by this probe (see Cautions).
Any patient with a FISH signal pattern indicating loss of the critical region will be reported as having a deletion of the region tested by this probe.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Because this FISH test is not approved by the FDA, it is important to confirm cri-du-chat syndrome diagnoses by other established methods, such as clinical history or physical evaluation.
Additional critical genes associated with cri-du-chat syndrome may lie distal to the loci in this probe set, and this test may give normal results if a microdeletion occurs outside the region tested by this probe. If this test is normal and the patientâ€™s phenotype is consistent with cri-du-chat syndrome, subtelometric FISH analysis may be warranted (FRTEL / Subtelomeric Region Anomalies, FISH).
FISH analysis was performed on a series of 10 patient peripheral blood or amniotic fluid samples and results were compared to cytogenetic or FISH telomere analyses and the patientâ€™s phenotype. Using a probe for the cri-du-chat (CDC) region at 5p15.2, this FISH analysis identified a deletion in 6 patients with a phenotype consistent with cri-du-chat syndrome or a cytogenetic or telomere 5p deletion. Four additional patients with chromosome abnormalities involving chromosome 5, but not containing the 5p15.2 deletion, were further characterized using this probe set. This demonstrated the probeâ€™s ability to define other chromosome 5 rearrangements in this region that are not consistent with 5p15.2 deletion. In a group of 34 patient samples (peripheral blood, tissue, or amniotic fluid) with a normal karyotype or FISH telomere analysis results, no deletions of the CDC region were identified. Two patients with normal results using this probe set were identified to have a more proximal 5p deletion using a telomere FISH analysis (see Cautions).
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Van Dyke DL, Witkor A: Chapter 26: Clinical cytogenetics. In Laboratory Medicine. Second edition. Edited by K McClatchey. Baltimore, MD. Williams and Wilkins, 2002
2. Jones K: Deletion 5p syndrome. In Smithâ€™s Recognizable Patterns of Human Malformation. Sixth edition. Philadelphia, Elsevier Saunders, 2005
3. Mainardi PC, Perfumo C, Cali A, et al: Clinical and molecular characterization of 80 patients with 5p deletion: genotype-phenotype correlation. J Med Genet 2001;38:151-158