Submicroscopic distal deletion of the long arm of chromosome 13(13q34) with corpus callosum agenesis

The 13q deletion syndrome phenotype was first described in 1969 [Allderdice et al., 1969] and comprises developmental delay, growth retardation, microcephaly, hypertelorism, a broad nasal bridge, micrognathia, hypoplastic or absent thumbs, hypoplastic kidneys, and ambiguous genitalia. Described central nervous system (CNS) anomalies are various comprising neural tube defects, holoprosencephaly, Dandy–Walker malformation and agenesis of the corpus callosum. The phenotypic description of the 13qsyndrome is thought to be dependent on the location and size of the deleted segment. Previously 13q deletions were assigned to three groups: Group 1 (deletions proximal to the presumed ‘‘critical region’’ q32 [Brown et al., 1995]) with growth deficiency, mild mental retardation and minor anomalies; Group 2 (deletions containing q32) with the most serious phenotype with growth deficiency, severe mental retardation, microcephaly, dysmorphic facies, gastrointestinal malformations, distal limb deficiencies and CNS malformations. The zinc finger protein of cerebellum 2 (ZIC2) gene maps to the 13q32.3 region and has been considered a candidate for CNS anomalies [Brown et al., 1995]; Group 3 (terminal deletions q33-34) with mental retardation but lack of major malformations and growth deficiency [Brown et al., 1995; Luo et al., 2000]. We report on a boy with a terminal 13q34 deletion with agenesis of the corpus callosum. A non-consanguineous couple was already prenatally followed in the second pregnancy because of fetal colpocephaly with suspicion of agenesis of the corpus callosum with normal prenatal karyotype 46,XY. He was born at 37 weeks (weight: 2,500 g; length: 48 cm; and head circumference: 34 cm). The diagnosis of agenesis of the corpus callosum was confirmed by ultrasound and MRI. Mental development was first evaluated at the age of 3 years with the Snijders-Oomen non-verbal intelligence test (SON-R test) [Snijders and Snijders-Oomen, 1958] and was normal. At age 6 years a Bayley developmental scale was done and resulted in a borderline intelligence (total IQ: 72; verbal IQ: 92; performance IQ: 59). At age 8 years his weight, length and head circumference were at the 50th centile. A repeat MRI confirmed agenesis of the corpus callosum without associated migration anomalies. At the age of 10 years he was not dysmorphic, and had sociable behavior but delayed motor skills. He was in a special school for Specific Learning Disabilities. Conventional karyotype is normal. A 1 Mb resolution BAC array comparative genomic hybridization (aCGH) shows a 4.4 Mb deletion of 13q34 between the flanking clones RP11-40E6 and RP11 -245B11 (Fig. 1a). Fluorescence in situ hybridization with probe RP11-310D8 confirmed the 13q34 deletion (Fig. 1b) that is de novo. The karyotype is 46,XY arr cgh13q34(RP11-17E4! RP11265C7) 1. Ballarati et al. [2007] reported molecular-cytogenetic characterization of 13q deletions in 14 patients confirming that those lacking the 13q32 band are more seriously affected. Two patients presenting a terminal 13q deletion but with involvement of 13q32 had agenesis of the corpus callosum and associated anomalies. Hindryckx et al. [2008] recently reported a first trimester prenatal diagnosis of 13qsyndrome with increased nuchal translucency, Dandy–Walker malformation and a small parietal encephalocele with a 13q deletion involving 13q32 (del(13)(q31.1q33.1)). But Luo et al. [2000] described a boy with a terminal 13q33-34 deletion and a lumbosacral myelomeningocele suggesting that haploinsufficiency of one or more genes mapping to 13q33-34 may be responsible for CNS malformation. The boy here is the first reported with a deletion distal to 13q32 (13q34) and agenesis of the corpus callosum as the sole major How to Cite this Article: Witters I, Chabchoub E, Vermeesch JR, Fryns J-P. 2009. Submicroscopic distal deletion of the long arm of chromosome 13(13q34) with corpus callosum agenesis.