Poster Presentation Australasian Society for Dermatology Research 2022 Annual Scientific Meeting

Rare amongst rare: An atypical case of ichthyosis vulgaris and recent genetic findings. (#12)

Noy Keller Rosenthal 1 , Eli Sprecher 2 , Ofer Sarig 2 , Alain Hovnanian 3 , Hugo Sampio 4 , Rani Sachdev 5 , Dedee F Murrell 1
  1. Department of Dermatology, St. George Hospital, University of New South Wales, Sydney, NSW, Australia
  2. Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel-Aviv University, Tel Aviv, Israel
  3. Department of Genetics, Necker hospital for sick children, INSERM U1163, Imagine Institute, Paris University, Paris, France
  4. Department of Neurology, Sydney Children's Hospital, Randwick, NSW, 2031, Australia
  5. School of Women's and Children's Health, UNSW Medicine, Sydney Children's Hospital, Randwick, NSW, Australia

Introduction: The ability to isolate the cause of several genodermatoses, has shed light on the critical function of various components of the epidermal barrier in the pathogenesis of allergic and atopic diseases(1,2). Genodermatoses sharing pathogenetic elements with atopic disorders, sometimes present with overlapping symptoms including: ichthyosis vulgaris(IV), Netherton syndrome, SAM syndrome and exfoliative ichthyosis(3–9).
We present the case of a 16 years old male with atypical ichthyosis vulgaris and multi-systemic disorders, some are overlapping with other genodermatoses involving epidermal barrier dysfunction.

 

Case presentation: Our patient was born full-term to non-consanguineous parents. His primary dermatological manifestations included: severe eczema- mainly flexural, xerosis and brittle hair. Feeding difficulties appeared early after birth and he required PEG feeding. During infancy, a gross motor lag was noted. In puberty, his skin involvement remained most prominent with severe atopic dermatitis responsive to dupilumab. Additionally, he had GH deficiency and progressing neurological symptoms.
Due to the multi-organ involvement, a panel of epidermal structural genes was performed. He was heterozygous for a semi-dominant mutation in FLG (consistent with IV), and for a variance-of-unknown-significance in SERPINB8, associated with exfoliative ichthyosis.
A trio exome revealed a pathogenic variant in MORC2. Heterozygous variants in MORC2 have been reported in individuals with Charcot-Marie-Tooth disease type 2Z. Our patient shares some of the clinical features reported in carriers(10,11).

 

Discussion: We suggest that our patient's atypical ichthyosis, may be attributed to the presence of a heterozygous SERPINB8 variant, classified to date as non-pathogenic, while his extra-dermal involvement is related to the MORC2 variant.
Another less likely explanation, is that the recently described MORC2 variant is responsible for his entire array of disorders, some are yet to be described in literature.
Lastly, we hypothesize that this is a case that can be explained by a yet to be identified skin structural gene mutation. 

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