Mal de Meleda Masquerading as Nagashima- Type Palmoplantar Keratoderma: A Genetically Confirmed Case from Pakistan

Farsom Ayub¹, Hira Tariq², Wahi Yasmin³, Uzma Amin4, Saelah Batool⁵, Faria Asad⁶

Keywords: Mal de Meleda, palmoplantar keratoderma, SLURP1, Nagashima-type keratoderma, SERPINB7, genetic diagnosis, consanguinity

DOI: 10.63475/yjm.v5i2.0400

DOI URL: https://doi.org/10.63475/yjm.v5i2.0400

Publish Date: 22-07-2026

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Pages: 431 - 436

Downloads: 7

Citation: 0

Author Affiliation:

1 Postgraduate Resident, Department of Dermatology, Services Hospital, Lahore, Pakistan
2 Dermatologist, Assistant Professor, Department of Dermatology, Services Institute of Medical Sciences/Services Hospital, Lahore, Pakistan
3 Medical Officer, Department of Dermatology, Services Hospital, Lahore, Pakistan
4 Dermatology, Senior Registrar, Department of Dermatology, Services Institute of Medical Sciences/Services Hospital, Lahore, Pakistan
5 Dermatologist, Associate Professor, Department of Dermatology, Services Institute of Medical Sciences/Services Hospital, Lahore, Pakistan
6 Dermatologist, Professor, Department of Dermatology, Services Institute of Medical Sciences/Services Hospital, Lahore, Pakistan

Abstract

Mal de Meleda (MDM) is a rare autosomal recessive palmoplantar keratoderma (PPK) caused by pathogenic variants in the SLURP1 gene. Its early clinical manifestations can overlap considerably with Nagashima-type palmoplantar keratoderma (NPPK), which is caused by biallelic variants in SERPINB7, creating diagnostic uncertainty. We describe a 36-year-old Pakistani male born of a consanguineous union, presenting with congenital PPK initially resembling NPPK clinically. Molecular testing using clinical exome sequencing identified a homozygous pathogenic nonsense variant in SLURP1 (c.286C>T; p.Arg96*), confirming autosomal recessive MDM. An additional heterozygous pathogenic missense variant in WNT10A (c.682T>A; p.Phe228Ile) was also identified. Progressive transgradient hyperkeratosis, hyperhidrosis, malodorous maceration, and recurrent dermatophyte superinfection supported the final diagnosis. This case underscores the importance of longitudinal clinical assessment combined with molecular genetic testing in hereditary PPKs with overlapping phenotypes, particularly in consanguineous populations. No pathogenic variants were identified in SERPINB7 on clinical exome sequencing, definitively excluding NPPK. It also highlights both the value of clinical exome sequencing for accurate diagnosis and genetic counselling, and the potential relevance of additional ectodermal variants such as WNT10A detected incidentally on comprehensive genomic panels.

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