A Girl with del(4)(q33) And Occipital Encephalocele: Clinical Description And Molecular Genetic Characterization of A Rare Patient

Abstract

We present clinical and developmental data on a girl with a de novo terminal deletion of the long arm of chromosome 4, del(4)(q33). The patient was evaluated at birth and followed up until 5 years of age. She showed facial and digital dysmorphism, a complex congenital heart defect, a large occipital encephalocele, and postnatal growth deficiency. Her neuropsychomotor milestones were delayed, and she developed learning difficulties. Apart from standard Giemsa banding, a molecular genetic analysis was performed using a comparative genomic hybridization (CGH) array. This revealed a terminal deletion at the band 4q32.3, which is directly adjacent to 4q33. The clinical findings in our patient differ from those described previously in patients with del(4)(q33) and del(4)(q32), respectively. In particular, the prominent occipital encephalocele has not been observed before in a terminal 4q deletion.

Terminal chromosome 4q deletion syndrome in an infant with hearing impairment and moderate syndromic features: review of literature

“…The patient we present was analyzed with a high resolution SNP array to delineate the deletion interval and the parental origin of the de novo rearrangement. We found it especially challenging to finely map disease-relevant intervals with the various low-resolution techniques that used GTG banding [7,10,13-15], FISH [16], and the different resolution arrays, including BAC aCGH [18], 1 Mb aCGH [19], 44 K aCGH [6,17,20], 105 K aCGH [9,22], and 300 K SNP array [21]. Another limitation includes possible variations in the depth of clinical descriptions listed, especially those from the DECIPHER database, which were not as detailed as the published cases.…”

12-year-old boy with a 4q35.2 microdeletion and involvement of MTNR1A, FAT1, and F11 genes

“…(2007) due to a 4q35.2 qter deletion (about 1.3 Mb in size) detected with a 32 K Bacterial Artificial Chromosome array (see Table 1 for summary). In addition, array comparative genomic hybridization was used to identify a de-novo terminal deletion of the long arm of chromosome 4, del(4)(q32.3) in a 5-year-old girl with facial and digital dysmorphism, a complex congenital heart defect, a large occipital encephalocele, postnatal growth deficiency, and developmental delay (Quadrelli et al ., 2007). In 2008, a 3-year-old boy with dysmorphic facial features, fifth finger clinodactyly, hypospadias, and severe developmental delay was reported to have a de-novo distal deletion of 4q33, detected at about 20 Mb in size by using a 1 M resolution array comparative genomic hybridization and subsequent fluorescent in-situ hybridization analysis (Kitsiou-Tzeli et al ., 2008).…”

Genotype–phenotype analysis of 4q deletion syndrome: Proposal of a critical region

“…The primary abnormalities in this group of patients are craniofacial malformation, developmental delay, and digital, skeletal, and congenital heart defects. Array CGH is an emerging technology for characterizing patients with 4q deletion syndrome in an attempt to elucidate genotype-phenotype correlations [Quadrelli et al, 2007b]. Recently, Li's group reported two patients with 4q deletions.…”

“…Recently, array CGH has been used to characterize patients with 4q deletions in an attempt to elucidate genotype-phenotype correlations [Quadrelli et al, 2007b;Kaalund et al, 2008;Kitsiou-Tzeli et al, 2008;Sensi et al, 2008;Hillhorst-Hofstee et al, 2009;Rossi et al, 2009;Al-Owain et al, 2010;Bonnet et al, 2010;Chien et al, 2010;Moreira et al, 2010]. Previously published reports are limited to a small number of cases.…”