A de novo complex karyotype with two independent balanced translocations and a double inversion of chromosome 6 presenting with multiple congenital anomalies.
We report a 4-year-old female with a de novo complex karyotype with multiple chromosomal rearrangements and a distinctive phenotype. Her medical history is significant for having been a twin born at 35 weeks gestation, breech presentation, with feeding problems and poor growth as an infant, gastroesophageal reflux disease, peripheral pulmonic stenosis, omphalocele, high myopia, and severe mental retardation. She is small for her age with microcephaly, posteriorly sloping forehead, shallow orbits, long palpebral fissures, prominent nose, wide mouth, absent uvula, kyphosis, brachydactyly, bridged palmar crease, and hypertonia. Peripheral blood lymphocytes revealed a karyotype of 46,XX,t(1;12)(p22.3;q21.3),inv(6)(p24q23),t(7;18)(q11.2;q21.2) in all cells. Parental karyotypes and that of her twin were normal. Spectral Karyotyping (SKY) and fluorescence in situ hybridization (FISH) with whole chromosome paints for chromosomes 1, 6, 7, 12, and 18 did not reveal additional rearrangements. Prometaphase G-banding analysis suggested that the "inverted" chromosome 6 might contain a cryptic rearrangement. Although no deletion nor duplication was detected using metaphase comparative genomic hybridization (CGH), multicolor high resolution banding (mBAND) demonstrated a double inversion of chromosome 6, resulting in a final karyotype as above but including der(6)(pter --> p23::q21 --> q22.3::q21 --> p23::q22.3 --> qter).
Department of Pediatrics, Greater Baltimore Medical Center, Baltimore, Maryland 21204, USA. Akline@gbmc.org
Antonie D
AD
Kline
Constance A
CA
Griffin
Mary H
MH
Haddadin
Ilse
I
Chudoba
Laura A
LA
Morsberger
Anita L
AL
Hawkins
R Stephen
RS
Amato
Gaurang
G
Munshi
Maimon M
MM
Cohen
D000015:Abnormalities, Multiple / Q000235:genetics*; D001741:Black or African American; D002675:Child, Preschool; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D032681:Spectral Karyotyping