Pathological Case of the Month

Figure 1. This full-body view includes the malformed ears (overfolding of the superior helix, underfolding of the posterior helix, and a prominent tragus).

Figure 2. The frontal (left) and oblique (right) views of the face show her broad nasal bridge and small nose.

Figure 3. Full karyotype showing 46,XX,del(10)(q26.1); arrow shows the deleted chromosome.

Figure 4. Partial karyotype showing pairs of chromosome 10 from 3 cells; the deleted chromosome is on the right. Region of deletion is shown on the ideogram at the left.

Initially, she would not nipple feed. When she did nipple feed, she would intermittently become cyanotic.

The gross and histopathological examination of the placenta revealed no abnormalities. The infant's karyotype is shown in Figure 3. Figure 4 shows the long arm of chromosome 10.

The infant's cytogenetic diagnosis is 46,XX,del(10)(q26.1). The q indicates the arm of the chromosome on which the deletion has occurred, and the 26.1 refers to the specific band where the break has occurred. The remaining chromosome consists of the entire short arm of chromosome 10 and part of the long arm lying between the centromere and band 10q26.1. Our review of the world's literature found that terminal deletions of chromosome 10 are uncommon, about 25 cases reported to date. The breakpoints for the terminal deletion of chromosome 10 have ranged from 10 q23≥q26.2, and the affected patients have a strikingly similar phenotype with a positive correlation between the increasing severity of their major malformations and the increasing size of their chromosome deletion.¹

Findings from the routine chromosome study of this patient were initially interpreted as normal. However, there was a strong index of suspicion on the basis of the patient's facial features, malformed ears (overfolding of the superior helix, underfolding of the posterior helix, and a prominent tragus), and hands. Another specimen of blood was sent to a second laboratory and the initial laboratory study was reinterpreted. The reinterpretation of the first study and the second consultation had the identical cytogenetic diagnosis of 10q deletion. Huang et al² recently reported the need for high-resolution chromosome studies and fluorescence in situ hybridization to make the diagnosis in the face of a high index of clinical suspicion.

Chromosome studies on this patient's parents were performed to determine if either parent carries a translocation involving the long arm of chromosome 10. Both parents had normal karyotypes, so this abnormality was a de novo deletion.

Ninety-five percent of the children with this cytogenetic diagnosis will have severe developmental delay. Serial neurodevelopmental testing reveals that she has substantial developmental deficits at 21 months of age (3- to 5-month gross motor skills and fine motor skills at 6 to 8 months). At 3 years of age, she walks with a gait trainer, is vocalizing, and making some vowel sounds. She has bilateral sixth nerve weakness and astigmatism, not uncommon for patients with 10q deletion.³

Almost half of the patients described in the literature have heart and urogenital defects.¹ This child had a normal renal ultrasonographic scan on her third day of life, but presented with high fever secondary to Escherichia coli bacteremia and urosepsis at 2 months of age. The ultrasonogram of her kidneys at this time revealed a dilated collecting system of the left kidney; a contrast-enhanced cystogram showed bilateral reflux and hydronephrosis to the level of the kidneys. No abnormalities of the bladder or urethra were noted. She was placed on a prophylactic antibiotic regimen, but continued to have recurrent infection and bilateral reflux at 1 year of age. Using cystoscopy both ureters could be seen entering the bladder near the bladder neck and each had an incompetent tunnel that was surgically treated (ureteral reimplantation) with good results.

The first description of a patient with terminal deletion of the long arm of chromosome 10 in association with a urinary tract abnormality had a strikingly similar course.⁴ At 7 months of age, after repeated urinary tract infections, the patient's evaluation revealed bilateral intrarenal reflux secondary to the absence of the submucosal ureteral tunnels with severe lateral displacement of the ureteral orifices. These defects, resulting in the impaired valvular mechanism of the ureterovesical junction were surgically corrected by a ureteral reimplantation procedure.⁴

Our patient's chromosome deletion, like most of the gross autosomal defects, occurred sporadically and the phenotypic effects were present at the end of the first month of embryonic life. At this time, only supportive therapy is available for chromosome qter deletion syndrome.⁵

Accepted for publication March 1, 1997.

Corresponding author: Dennis T. Costakos, MD, Franciscan Skemp Healthcare Mayo Health System, 700 W Ave S, La Crosse, WI 54601 (e-mail: ddcostako@fsh.mayo.edu).