MALTA syndrome

In 1961, Nicolau and Balus described individuals with benign skin lesions, including atrophodermia vermiculata, multiple syringomas and milia, which became known as Nicolau-Balus syndrome and were characterized by an irregular distribution of elastin fibers (Nicolau and Balus, 1961). A similar phenotype was later described by Michaëlsson et al. (1981) as Rombo syndrome, in which the elastin distribution in some areas of the dermis looked like "swaths of steel wool" (van Steensel et al., 2001). In 2010, Schaller et al. described several cases with the same abnormal elastin distribution and the additional feature of sweat gland proliferations that are morphologically similar to those found in patients with microcystic adnexal carcinoma, but which do not behave destructively or malignantly and do not require surgical resection.

Very rare syndrome defined by a hsitological and genetic constellation. Histologically, it is characterized by benign, diffuse syringosquamous hyperplasia, severe elastosis of the dermis and mutations in the MYH9 gene. The dermatological-clinical correlate is described as atrophodermia vermiculata (Bertlich I et al. 2024). The gene codes for a protein of the same name (myosin heavy chain 9), a non-muscle myosin (NMIIA). These proteins are an important component of the cellular cytoskeleton. The MYH9 protein plays a central role in various cellular processes.

Mutations are present in the MYH9 gene (transcript ENST00000216181.9, a missense variant/ c.2012C>T), which is considered pathogenic for protein function. Furthermore, missense variants (c.706G>T and c.694_695delinsAA) were detectable, which also led to this phenotype. Both variants lead to a single amino acid change. The size and number of blood platelets are normal in this variant of MALTA syndrome. Likewise, no hearing disorders or bleeding irregularities are detectable. Ultimately, the syndrome is based on a pathogenic non-muscle myosin. The connection between the pathogenic connective tissue structures and the pseudotumorous sweat gland proliferations is unclear.

In skin fibroblasts, expression of NMMIIA increases during dermal wound healing and scar tissue remodeling, in which extracellular fibroblasts secrete extracellular matrix components including elastin (Bond et al.2011). Expression of NMMIIA has been shown to increase when dermal elasticity decreases (Bond et al., 2011), and this may explain the phenotype in MALTA syndrome.

Individuals with MALTA syndrome show similarities to Nicolau-Balus and Rombo syndromes , with some cases also showing microcystic adnexal carcinoma-like ductal proliferations (Fostier W et al. 2023).

Pseudotumorous proliferations of eccrine sweat glands can also be found in scleromyxedema (Bertlich I et al. 2024).

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3. Fostier W et al.(2023) Squamous cell carcinoma and MYH9-associated elastin aggregation (MALTA) syndrome. Clin Exp Dermatol 49:105-107.
4. Fewings E et al. (2019) Malta (MYH9 Associated Elastin Aggregation) Syndrome: Germline Variants in MYH9 Cause Rare Sweat Duct Proliferations and Irregular Elastin Aggregations. J Invest Dermatol 139:2238-2241.e6.
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6. Mentzel J et al. (2021) Sweat duct proliferation associated with aggregation of elastic tissue and atrophodermia vermiculata: a simulator of microcystic adnexal carcinoma - a family with MALTA-syndrome. J Dtsch Dermatol Ges 19:1052-1056.
7. Michaëlsson G et al. (1981) The Rombo syndrome: a familial disorder with vermiculate atrophoderma, milia, hypotrichosis, trichoepitheliomas, basal cell carcinomas and peripheral vasodilation with cyanosis. Acta Derm Venereol 61:497-503
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9. Namiki T et al. (2017) Image Gallery: Microcystic adnexal carcinoma (syringomatous carcinoma and sclerosing sweat duct carcinoma) as an extensive sclerotic erythematous plaque with telangiectasia over the face. Br J Dermatol 176:e122
10. Verver EJ et al. (2016) Nonmuscle Myosin Heavy Chain IIA Mutation Predicts Severity and Progression of Sensorineural Hearing Loss in Patients With MYH9-Related Disease. Ear Hear 37:112-120.