The limits of clinical findings in similar phenotypes, from Carpenter to ATRX syndrome using a whole exome sequencing approach: a case review

Abstract

Background: The diagnostic process for uncommon disorders with similar manifestations is complicated and requires newer technology, like gene sequencing for a correct diagnosis.

Main body: We described two brothers clinically diagnosed with Carpenter syndrome, which is a condition characterized by the premature fusion of certain skull bones (craniosynostosis), abnormalities of the fingers and toes, and other developmental problems, for which they underwent craniotomies. However, whole exome sequencing analysis concluded a novel pathological variation in the ATRX chromatin remodeler gene and protein remodeling demonstrated structural variations that decreased the function, giving a completely different diagnosis to these patients.

Conclusion: Our study focuses on the importance of using newer technologies, such as whole exome sequencing analysis, in patients with ambiguous phenotypes.

Keywords: ATRX syndrome; Rare diseases; Whole exome sequencing.

Fig. 1

Patient 1 at 11 years old. a–c Hands abnormalities (clinodatlily, camptodactily, and brachydactlyly)

Fig. 2

Patient 2 at 10 years old. a–d Hands abnormalities (clinodatlily, camptodactily, and brachydactlyly)

Fig. 3

Family Pedigree. It is shown the two brothers and the half-sister with similar physical characteristics but no intellectual disability

Fig. 4

Affected amino acid neighborhood analysis. a, b Structural neighborhood Wt and mutant M2171V respectively. Notice how intrahelical and structural hydrogen bonds change when compare. c, d One on one bond neighborhood of Wt and mutant M2171V respectively. See how differential bond conformation is made with adjacent amino acids