Ichthyosis bullosa of Siemens: its correct diagnosis facilitated by molecular genetic testing

Abstract

Ichthyosis bullosa of Siemens (IBS, MIM 146800) is a unique congenital ichthyosis characterized by mild epidermal hyperkeratosis over flexural areas, blister formation and the development of superficially denuded areas of hyperkeratotic skin. It is clinically difficult to distinguish severe IBS from mild bullous congenital ichthyosiform erythroderma (BCIE, MIM 113800). In the current literature, 19 IBS families with keratin 2e (K2e) mutations have been reported, despite only five IBS families having been reported before the first identification of K2e mutation in 1994. We studied four patients from three Japanese IBS families. They had previously been misdiagnosed as having BCIE before the correct diagnosis was made after mutation detection. To detect the pathogenic mutations, we performed direct sequencing of the entire coding regions of KRT2E encoding K2e in the patients and healthy family members. K2e mutations, a 1469T-->C transition (L490P) and a 1477G-->A transition (E493K) within the conserved 2B helix termination motif of the rod domain were detected in the families and the definite diagnosis of IBS was made in the four cases. The present results indicate that IBS is not such a rare entity as was previously thought, and accurate diagnosis is now available by mutation analysis.

Molecular and diagnostic aspects of genetic skin fragility

“…A progressive amelioration of symptoms with age is reported. Clinical and histopathological differentiation from EHK is difficult [30], since histology of IBS reveals several features of epidermolytic hyperkeratosis. However, vacuolization of the keratinocytes is less dominant and more superficial than that observed in EHK.…”

Ichthyosis bullosa of Siemens

“…8 Patients with IBS who had severe skin phenotypes have previously been misdiagnosed with BCIE from their clinicopathological findings. 9 Conversely, mild BCIE can show clinical and histological features similar to IBS. 4 Due to this, laboratory investigation is often needed to arrive at a correct diagnosis as the two share clinical similarities.…”

Inherited Keratinization Disorders

“…Biyopi kesitlerinde hafif hiperkeratoz, stratum spinozumun üst kısımlarında lizis vardır. Moleküler düzeyde KRT2 gen mutasyonu saptanır [19][20][21] .…”