A case of Beckwith-Wiedemann syndrome caused by a cryptic 11p15 deletion encompassing the centromeric imprinted domain of the BWS locus.

Marcella Zollino¹, Daniela Orteschi¹, Giuseppe Marangi¹, Agostina De Crescenzo², Vanna Pecile³, Andrea Riccio², Giovanni Neri^1,*

¹ Istituto di Genetica Medica, Università Cattolica Sacro Cuore, Policlinico "A.Gemelli", Roma, Italy;
² Dipartimento di Scienze Ambientali, Seconda Università di Napoli, Caserta, Italy;
³ Unità di Citogenetica, IRCCS "Burlo Garofalo, Trieste, Italy

Correspondence to: Giovanni Neri, Genetica Medica, Università Cattolica del S. Cuore, Istituto di Genetica Medica, Universita Cattolica, Largo F Vito 1, Roma, 00168, Italy; gneri{at}rm.unicatt.it

Accepted 16 September 2009

Beckwith-Wiedemann syndrome is a clinically variable and genetically heterogeneous disorder, providing evidence that imprinted genes play key roles in the control of fetal growth. Clinically, diagnostic criteria include macrosomia, macroglossia, abdominal wall defects, neonatal hypoglycemia, visceromegalies and hemihyperplasia. Component clinical manifestations also include renal abnormalities, adrenocortical cytomegaly and a characteristic facial appearance, with midface hypoplasia and ear anomalies. Genetically, BWS is associated with disturbances within two different domains on 11p15 that are controlled by distinct Imprinting Control Regions, ICR1 and ICR2. The majority of patients have abnormalities within ICR2. In particular, loss of maternal methylation accounts for 50-60% of cases, and is associated with reduction in the expression of the CDKN1C gene, a member of the cyclin-dependent kinase inibitor family acting as negative regulator of cell proliferation. Mutations in CDKN1C are detected in another 5-10 % of subjects with sporadic BWS. Chromosome deletions affecting ICR2 are uncommon. We report on a patient with BWS in which a de novo 11p15 deletion was detected by array-CGH. The deletion, that was maternal in origin, encompassed ICR2 and several flanking genes, including CDKN1C. A normal methylation pattern of ICR1 was observed, supporting the model of two independent domains within the BWS locus.

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