Cloves syndrome Q85.9

Friedberg Hermann 1867

CLOVES is the acronym for a segmental overgrowth syndrome, "PIK3CA-related overgrowth spectrum" (PROS), and is characterized by the following symptoms: congenital lipomatous overgrowth, vascular malformations, epidermal nevus, skeletal anomalies.

This is caused by germline mutations in the mosaic in the PIK3Ca gene, which is located on chromosome 3q26.32. The gene codes for the PIK3-alpha protein.

A trunk-accentuated port wine nevus (nevus flammeus), sometimes combined with venous vascular malformations, is particularly typical

• Congenital circumscribed tall stature, especially of the feet, which increases in the course of life. The "sandal gap" is typical.
• Lipomatosis, lipomas, especially on the trunk.
• Bone changes, especially scoliosis.
• Epidermal nevus
• Possible asymmetry of the skull, epilepsy, hemimegalencephaly, beam deficiency

Other syndromes that simulate brain overgrowth include megalencephaly-polydactyly-polymicrogyria-hydrocephalus syndrome (MPPH), in which megalencephaly occurs in association with distal limb abnormalities such as postaxial polydactyly and hydrocephalus. Another disease associated with megalencephaly and skin manifestations is Bannayan-Riley-Ruvalcaba syndrome (BRRS) (Sarma K et al. 2022).

Examples of the clinical diversity of the PIK3CA-related overgrowth spectrum (PROS) are known with overlapping features of CLOVE syndrome (Congenital Lipomatous Overgrowth Vascular malformations Epidermal nevi and Skeletal abnormalities) and MCAP syndrome (Megalencephaly-Capillary malformation Polymicrogyria) (Denorme P et al. 2018).

1. Denorme P et al. (2018) Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-related overgrowth spectrum: A brief report. Pediatr Dermatol 35:e186-e188.
2. Eissing M et al.(2019) PTEN Hamartoma Tumor Syndrome and Immune Dysregulation. Transl Oncol 12:361-367.
3. Pilarski R et al. (2019) PTEN Hamartoma Tumor Syndrome: A Clinical Overview. Cancers (Basel)11:6
4. Sarma K et al. (2022) Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome (MCAP): A Rare Dynamic Genetic Disorder. Cureus 14:e25123.