A Rare Genetic Cause of Erythrodermic Ichthyosis: Chanarin–Dorfman Syndrome

Dear Editor, Syndromic ichthyoses are a group of cornification disorders characterized by generalized skin scaling and hyperkeratosis, along with symptoms affecting other organ systems.[1,2] A thorough understanding of the unique combination of signs present in each syndromic form of ichthyosis plays a crucial role in reaching a successful diagnosis. Chanarin–Dorfman syndrome (CDS) is a rare autosomal recessive neutral lipid storage disease affecting multiple systems. The syndrome is caused by mutations in the ABHD5 gene (also known as CGI-58), located on chromosome 3p21, leading to the accumulation of lipid droplets in various cell types, including hepatocytes, granulocytes (Jordan’s anomaly), and skin fibroblasts. To date, around 100 cases of CDS have been reported globally, mainly from the Mediterranean regions, Turkey and the Middle East. CDS is an uncommon cause of erythrodermic ichthyosis.[3] We present a rare case of erythrodermic ichthyosis in a 15-year-old boy with underlying CDS. A 15-year-old boy was referred to our dermatology clinic for generalized, erythematous, itchy, dry skin with scales. He had multiple medical issues, including synovitis, liver steatosis, and esophageal varices, and had been treated in Afghanistan. His parents were first cousins, indicating consanguinity. The patient had delayed motor milestones, walking independently at 6 years of age, along with sensorineural hearing loss and learning disabilities. We made a provisional diagnosis of ichthyosiform erythroderma. The possibility of an underlying metabolic disorder, immunodeficiency, and malignancy were considered; pediatrics and other specialties were consulted. Further evaluations revealed hepatomegaly, splenomegaly, leukopenia, thrombocytopenia, and cirrhosis. Given the complex medical history, genetic testing was performed, which confirmed a homozygous pathogenic variant of the ABHD5 gene, c.1006G >T (p.Glu336*); predicted to result in a premature stop codon in exon 7 (the last exon of ABHD5). This finding was diagnostic of CDS. His mother recalled significant skin issues shortly after birth, which necessitated a week-long hospitalization and respiratory support. Initially, he had dry skin accompanied by areas of fine scaling and erythema, predominantly on the extensor surfaces of the upper and lower limbs. However, over time, the scaling and erythema spread, gradually involving the trunk, face, and scalp. By the time he first presented to us, more than 90% of his body surface area was affected. On examination, diffuse xerosis, fine white scaling, and faint erythema were observed throughout the body, with erythema being more prominent on the face. Hyperkeratosis and adherent brown scaling were noted in the bilateral antecubital fossae and on the dorsal ankles. The scalp exhibited diffuse scaling. Additionally, no ectropion, eclabium, scalp alopecia, or nail dystrophy were present [Figure 1a-c].Figure 1: (a) Prominent facial erythema with fine scaling, accompanied by diffuse scalp scaling in a 15-year-old boy; (b, c) diffuse xerosis, fine white scaling, and faint erythema observed across the trunk, affecting more than 90% of the body surface areaHistopathological findings revealed mild acanthosis, thickening of the stratum corneum with focal mild parakeratosis, hypogranulosis and superficial dermal vascular dilatation, and no dermal infiltrates. Based on the medical history, clinical features as described above, and the histopathology results, the diagnosis of CDS was established. Notably, two of his three full siblings were also affected by ichthyosis. The differential diagnoses and phenotypic mimickers of CDS, along with key distinguishing clinical, systemic, and diagnostic features are shown in Tables 1a and 1b.[4,5]Table 1a: Differential diagnoses of Chanarin–Dorfman syndrome and key distinguishing featuresTable 1b: Erythrokeratoderma- and PRP-like phenotypic mimickers of Chanarin–Dorfman syndromeOur management was focused on symptomatic relief, including wet wraps with triamcinolone 0.1% ointment twice daily and tretinoin 0.1% cream at night, and dilute bleach baths two to three times per week for skin care. Systemic retinoid therapy was discussed as an option, but with caution due to potential hepatic toxicity. After counselling, appropriate follow-up was arranged, and the family was encouraged to join the Foundation for Ichthyosis Related Skin Types (FIRST) for support. The clinical variability of CDS arises from allelic heterogeneity, with 78 mutations identified, including splice-site mutations, insertions, deletions, nonsense, and missense mutations. Genetic testing for ABHD5 is crucial.[6,7] The most common is c. 594insC p.N209X.[8] Hepatomegaly/hepatitis is the most frequent manifestation, seen in 60% of cases, followed by myopathy, ocular issues, deafness, and splenomegaly. Authors’ contributions All authors have read and approved the manuscript. They meet the authorship criteria and confirm that the manuscript represents honest and original work. Data availability statement The data underlying this article will be shared on reasonable request to the corresponding author. Declaration of patient consent The authors certify that they have obtained all appropriate parent consent forms. In the form a parent has given their consent for the patient’s images and other clinical information to be reported in the journal. The parent understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Use of artificial intelligence (AI) The preparation of this manuscript was carried out entirely by the authors without the use of artificial intelligence technologies.