Cloves syndrome: A rare disorder of overgrowth with unusual features – An uncommon phenotype?

Abstract

CLOVES syndrome characterized by C ongenital L ipomatous O vergrowth, V ascular malformations, E pidermal nevi, and S keletal anomalies is a recently described sporadic syndrome from postzygotic activating mutations in PIK3CA . This 3-year-old boy, born to nonconsanguineous and healthy parents, had epidermal verrucous nevus, lower limb length discrepancy and bilateral genuvalgum, anterior abdominal wall lipomatous mass, central beaking of L2 and L3, and fibrous dysplasia of the left frontal bone. Ocular and dental abnormalities (ptosis, esotropia, delayed canine eruption, dental hypoplasia), ipsilateral asymmetrical deformity of skull, and large left cerebral hemisphere with mild ipsilateral ventriculomegaly were peculiar to him denoting an uncommon phenotype. The parents did not consent for magnetic resonance imaging and genetic studies because of financial constraints. The CLOVES syndrome has emerged as an uncommon yet distinct clinical entity with some phenotypic variations. Its diagnosis is usually from cutaneous, truncal, spinal, and foot anomalies in clinical and radioimaging studies. Proteus syndrome remains the major differential.

CLOVES syndrome caused by mosaic mutation in the PIK3CA gene identified in fibroblasts

“…Central nervous system manifestations include hemimegalencephaly, polymicrogyria, a 4-layered cortex, abnormalities of the gray and white matter, ventriculomegaly dysgenesis of the corpus callosum, neuronal migration defects leading to seizures, tethered spinal cord, and neural tube defects [9]. Patients with CLOVES syndrome have various degrees of intellectual disability.…”

“…Our patient firstly underwent targeted examination of the PIK3CA gene in chosen exons (2,6,8,9,20) by Considering the proband's phenotype we prioritized a somatic missense heterozygous variant in the PIK3CA gene (hg19; chr3:g.178928079G>A, NM_006218.4:c.1357G>A, p.(Glu453Lys) (Fig. 4A).…”

A Review on Cutaneous and Musculoskeletal Manifestations of CLOVES Syndrome

“…CLOVES syndrome (OMIM number 612918) is a recently described rare, sporadic (non-hereditary) complex mosaic overgrowth syndrome. 1–3 It was initially described in 2007 by Sapp et al as a novel overgrowth syndrome and entitled as “CLOVE” syndrome. 4 Although “CLOVE” syndrome had overlapping features with other overgrowth syndromes such as Proteus syndrome, the affected patients could not fulfill the established diagnostic criteria for the other disorders.…”

“… 7 The term “CLOVES” is an acronym denoting congenital lipomatous overgrowth, vascular malformations, epidermal nevi and spinal (scoliosis) and/ or skeletal anomalies. 1 , 2 , 8–13 …”

SOLAMEN Syndrome in a Filipino Child

“…This condition has been attributed to mutations in the PIK3CA gene located in chromosome 3q26.32. 5 SOLAMEN syndrome also referred to as segmental overgrowth, lipomatosis, arteriovenous malformation, and epidermal nevus syndrome or type 2 segmental Cowden syndrome, relates to the early loss of heterozygosity at the phosphatase and tensin homolog (PTEN) allele in the affected tissues in patients with underlying germline PTEN mutation. 6 Here we presented a case of a Filipino child with asymmetric overgrowth, epidermal nevus, lipomatosis, skeletal abnormalities, and vascular malformations, which are overlapping features of Proteus syndrome, CLOVES syndrome, and SOLAMEN syndrome.…”