Atypical Down Syndrome phenotype with translocation Trisomy 21

Down Syndrome (DS) is the most common chromosomal aneuploidy. Ninety-five percent of DS cases are due to free Trisomy while 3-4% are due to an unbalanced translocation. Generally, there are no phenotypic differences between these two causes of DS. We report an infant with Trisomy 21 due to 21q 21q translocation, who presented with an atypical DS phenotype. The proband was an AGA 36-week gestation infant born by SVD to a 35y.o. G2P2AB1 woman following two normal prenatal ultrasounds and a normal MSAFP. Pregnancy, labor and delivery were uncomplicated. At 2.5 months, exam revealed ht at 10-25th %, wt and HC at <5th%, mild facial asymmetry, high mildly deviated nasal bridge, downslanting palpebral fissures, absent Brushfield spots, moderate micrognathia, left ptosis, low set ears with overfolded superior helices, right Bell's palsy, left torticollis. Other findings were dermatoglyphics: right WRWAU, left ARUUU, tapered fingers with positional clenching of fist, sacral dimple and neurological abnormalities of hypertonia and arching of the back. Vision, hearing and echocardiogram were normal. By diagnostic criteria published in the J. of Peds. (1982), she did not meet the diagnosis of DS. Chromosome analysis by two laboratories at band level KI 550 revealed: 46,XX, +21, der (21; 21)(q10; q10). Both parents had normal karyotypes. FISH analysis utilizing the TUPLE; LSI 13,21 probe confirmed the Trisomy 21 translocation. At 8 months, she has continued hypertonia and developmental delay with functioning at 5-6 months. Our patient with Trisomy 21 due to translocation does not have the characteristic phenotype of DS. In 1977, Avramopoulos et al (1997) reported a patient with full standard Trisomy 21, who also had atypical phenotypes for DS. Possible etiologies for these findings may include: 1) small molecular deletion of the critical region of chromosome 21, 2) disruption of a gene by gene- gene interaction or 3) mosaicism in other cell lines. Further molecular research studies are planned.