14q32 deletion syndrome: a clinical report

The advent of chromosomal microarray analysis continues to lead in the discovery of microdeletion/microduplication syndromes not previously recognized (Masurel-Paulet et al., 2010), and to the better characterization of chromosome breakpoints identified by G-banded preparations (Butler et al., 2008). It is becoming an essential tool in expanding our knowledge about phenotypic variation of recognized cytogenetic syndromes, and in gaining a better understanding of the genome and its relationship to health and disease (Bejjani and Shaffer, 2008; Liang et al., 2008; Shinawi and Cheung, 2008; Edelmann and Hirschhorn, 2009; Wilsonet al., 2009; Fruhman and Van den Veyver, 2010; Manning and Hudgins, 2010; Miller et al., 2010).

The previous report by Youngs et al. (2011) gave a clinical description of an adult with a 14q32 deletion identified by G-banded chromosome analysis with further characterization by chromosomal microarray studies and a review of similarly affected individuals reported in the literature. Deletions of the chromosome 14q32 band are relatively rare with 12 reported patients to date. Hence, we report a new infant recently evaluated with dysmorphic features, developmental delays, and a weak high-pitched cry. Chromosomal microarray analysis was ordered and a de-novo 6.1-Mb deletion of the 14q32.2–32.1 region was found along with a 250-kb duplication of chromosome 1p36.22. We wish to add the report of our case to the medical literature.

Clinical report

Our patient was the product of a second pregnancy, but the first child born to nonconsanguineous parents. She was born at 34 weeks gestation complicated by oligohydramnios with intrauterine growth retardation. Congenital heart disease consisting of a bicuspid aortic valve was detected shortly after birth. Due to failure to thrive and feeding difficulties, a gastrostomy tube was placed at 3 months of age. She failed the newborn hearing screen, and fluid was identified in her middle ear. She had one seizure during the neonatal period and was placed on phenobarbital until 3 months of age. Strabismus was also noted at birth. She rarely cried, but the cry was weak and high pitched, similar to a cat cry.

On clinical examination at 8 months of age, her height was 62.8 cm (10th centile), weight was 5.19 kg (< 3rd centile), and head circumference was 42 cm (25th centile). She had a narrow and towering forehead with prominent veins, broad and flat nasal bridge, micro-gnathia, small mouth, thin upper lip, long eyelashes, and protruding, prominent low-set ears with poor architecture (Fig. 1). She had a large, soft anterior fontanel. Her nipples were small and positioned lower than normal. The hands were small and clenched with deep palmar creases. Her feet were also small and the fifth toe overlapped the fourth toe bilaterally. A gastrostomy tube was in place. Eczema was present involving several regions of the body. Significant global developmental delays were noted. She could not sit unassisted nor roll over. She continued to have a weak high-pitched cry.

Fig. 1.

Frontal and profile facial views of our patient with the 14q32.2 deletion at 8 months of age, showing her small mouth, thin upper lip, micrognathia, and prominent, protruding, low-set ears.

Chromosome analysis performed shortly after birth showed a 46,XX karyotype. Later, chromosomal micro-array analysis [array comparative genomic hybridization (aCGH)] was performed commercially using the 105 K ‘CMDX’ Oligo HD Scan (Combimatrix Molecular Diagnostics, Irvine, California, USA) to rule out a 5p deletion. The aCGH study showed a normal chromosome 5, but a 6.1-Mb deletion of the 14q32.2–32.1 region (Fig. 2) involving approximately 75 genes (chromosome 14: 11 291 796–11 539 047) and in addition, a 250-kb duplication of chromosome 1p36.22 band involving only one gene (PTCHD2). The duplication of 1p36.22 was thought to have little effect on the patient's phenotype. Parental studies were normal.

Fig. 2.

Chromosome microarray hybridization showing the location of the 6.1-Mb deletion from the 14q32.2–32.1 region.

Discussion

Twelve patients described in the literature with a cytogenetic deletion of chromosome band 14q32 have been summarized by Youngs et al. (2011). Common physical anomalies seen in at least 50% of the reported patients with the 14q32 deletion included a broad and flat nasal bridge, telecanthus, a high-arched palate, hypotonia, a broad philtrum, thin upper lip, blepharophimosis, a prominent forehead, a small mouth, downslanting palpebral fissures, a pointed chin, and malformed ears.

Our infant presented with features seen in other previously reported patients with the 14q32 deletion, but in addition, had a cat-like cry. Interestingly, a cat cry has been reported previously in a 3-year-old female patient with the 14q32 deletion syndrome (Ortigas et al., 1997). Small and lower positioned nipples, prominent and protruding ears, eczema, and small hands and feet were present in our infant, but not in common with other reported cases.

With the use of new genetic testing methods, more specific and detailed genetic information is now available at the DNA level to further characterize the size and, more precisely, the location of deletions or duplications in the genome. Therefore, the variability seen in clinical presentation of individuals with the same reported chromosome deletion by routine cytogenetic analysis may be further explained by comparing the size and position of the deletion using aCGH. For example, the recently reported patient with the 14q32 deletion by Youngs et al. (2011) using microarray analysis did not share the same deletion at the DNA level with our infant although both would be classified as having the 14q32 deletion syndrome. The large size of this deleted segment of chromosome 14q32 and many genes involved make genotype–phenotype correlation difficult to perform. The researchers encourage the report of additional individuals with these chromosome findings with more precise localization of the deletion breakpoints by microarray analysis for better genotype–phenotype correlation studies.