Deletion of 8q24 in an adult with mild dysmorphic features, developmental delay, and ketotic hypoglycemia

Abstract

We present a 56-year-old female with a history of carbohydrate intolerance and ketotic hypoglycemia, dysmorphic features, mild developmental delay, lymphedema, altered pain sensation, and frequent fractures, who was found to have a heterozygous 8.09 Mb deletion of chromosome 8q24.11q24.13 containing more than 39 genes, as well as a duplication of 20q11.23 containing one gene. The deleted region overlaps that of two previously reported patients, who share a subset of clinical characteristics with the patient described here. Some of this patient's clinical features are consistent with the loss of genes in the deleted region. The diagnostic work-up of this patient clearly demonstrates the evolution of genetic testing techniques.

Figure 1

Face and extremities of the patient, showing facial manifestations at 56 years of age, including sparse hair, a broad and high forehead, midface hypoplasia, a broad nose with a bulbous tip, a long and smooth philtrum and a thin upper lip. Hand photos show brachydactyly, and clinodactyly.

Figure 2

Photos of the patient at various ages demonstrating the progression of the facial phenotype. At younger ages, the broad and high forehead, thick eyebrows and midface hypoplasia are quite apparent, and the appearance of hypertelorism is more pronounced at younger ages. Signs of premature aging are first apparent in the photo at age 29 years. Not all ages are known. Photo a: 6 years of age; Photo b: 8 years; Photo c: 29 years.

Figure 3

Deletions of the patient described here and two previously reported patients [Wuyts et al., 2002; McBrien et al., 2008], showing the region of common deletion (indicated by the shaded square), as well as the other proven deleted genes in the interval (in gray) and the flanking genes known not to be deleted (in black). An ideogram showing the estimated deleted regions is also depicted (bottom left).