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PATIENT STORY

A 45-year-old black man presents with greasy scale over his face and large parts of his chest and back (Figure 214-1). A previous biopsy was diagnostic for Darier disease. His mother has the same condition. Other siblings are similarly affected (Figure 214-2). The patient has suffered with this condition for his entire life and believes that he has been ostracized from normal social life because of his appearance and body odor. He suffers from depression and has used various substances to treat his pain. Topical steroids provide some help for the itching and scaling, but the patient is looking for a more effective treatment. The cost of oral retinoids is currently prohibitive, but an application has been put in for patient assistance to receive acitretin.

FIGURE 214-1

Darier disease with greasy scales and hyperkeratotic and hyperpigmented papules and plaques in a seborrheic distribution involving the neck and chest. He has similar lesions on the back and scalp and in the groin. Sunlight and heat make his disease worse. (Reproduced with permission from Richard P. Usatine, MD.)

FIGURE 214-2

Darier disease present in three siblings. Their mother also has the disease. (Reproduced with permission from Richard P. Usatine, MD.)

INTRODUCTION

There are more than 100 genetic syndromes with cutaneous manifestations that are referred to as genodermatoses. For example, there are disorders of pigmentation (albinism), cornification (the ichthyoses and Darier disease), vascularization (Sturge-Weber syndrome), connective tissue (Ehlers-Danlos syndrome), porphyrin metabolism, other errors of metabolism (phenylketonuria), the immune system (Wiskott-Aldrich syndrome), and DNA repair (ataxia-telangiectasia and xeroderma pigmentosa), to name a few. Some textbooks are dedicated to the topic of genodermatoses alone.1 This chapter introduces the topic and illustrates a couple of genodermatoses. We have chosen two disorders of cornification as an introduction to the genodermatoses: Darier disease and X-linked ichthyosis.

EPIDEMIOLOGY

  • Darier disease (keratosis follicularis)—1:30,000 to 1:100,000. Males and females are equally affected. Clinically becomes apparent near puberty.

  • X-linked ichthyosis—1:2000 to 1:6000 males. Clinical lesions present typically during the first 1 to 2 months of life.

ETIOLOGY AND PATHOPHYSIOLOGY

  • Darier disease—An abnormal calcium pump in the sarco-/endoplasmic reticulum, SERCA2, results from a gene mutation in the ATP2A2 gene. It is inherited in an autosomal-dominant fashion and results in abnormal epidermal differentiation.

  • X-linked ichthyosis—A deletion of the steroid sulfatase gene results in keratinocyte retention by inhibiting degradation of the desmosome. It is inherited in an X-linked recessive manner.

DIAGNOSIS

DARIER DISEASE

  • Clinical features—Greasy, hyperkeratotic, yellowish-brown papules in a seborrheic distribution (Figures 214-1, 214-2, 214-3). The feet can be covered ...

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