Cutaneous Mosaic Disorders Naevi & Naevoid skin disorders : Complex vascular malformations and cutaneous and subcutaneous vascular tumors



PHACE is an acronym used to describe a syndrome characterised by the association of Posterior fossa brain malformations, large facial Haemangiomas, anatomical anomalies of the cerebral Arteries, aortic coarctation and other Cardiac anomalies, and Eye abnormalities. Sternal anomalies are also sometimes present, and in these cases the syndrome is referred to as PHACES. Two additional manifestations have been added to the clinical spectrum of PHACE syndrome: stenosis of the vessels at the base of the skull and segmental longitudinal dilations of the internal carotid artery. Newborns and infants are affected. Expression of the complete clinical picture of PHACE syndrome is extremely rare and most patients display only a partial phenotype (or incomplete clinical spectrum). The posterior fossa malformations include cerebellar hypoplasia, arachnoid cysts, cortical dysgenesis and Dandy-Walker malformation. The capillary haemangiomas have the same morphological, clinical and evolutive characteristics as those of sporadic benign haemangiomas. Intracranial and subarachnoid lesions may occur concurrently, with the intracranial lesions evolving in the same manner as the maxillofacial or cervical haemangiomas.

CLOVE syndrome

CLOVE syndrome is characterized by Congenital Lipomatous Overgrowth, progressive, complex and mixed truncal Vascular malformations, and Epidermal nevi.
Patients also present with disproportionate fat distribution. CLOVE syndrome may be associated with varying degrees of scoliosis and enlarged bony structures without progressive bony overgrowth. The presence of scoliosis/skeletal manifestations has lead to the suggestion that the acronym CLOVE should be expanded to CLOVES. In contrast to the bony distortion characteristic of Proteus syndrome (see this term), distortion in CLOVE syndrome occurs only following major surgery. Cranial asymmetry and central nervous system manifestations (generalized seizures, hemimegalencephaly, dysgenesis of the corpus callosum and neuronal migration defects) have been reported occasionally.

Proteus syndrome (PS)

Proteus syndrome (PS) is a very rare and complex hamartomatous overgrowth disorder characterised by progressive overgrowth of the skeleton, skin, adipose, and central nervous systems. Neonates usually appear normal at birth. Onset usually occurs from 6-18 months of age with asymmetric overgrowth seen mainly in the hands or feet. Macrodactyly is the most common presenting symptom, along with hemihypertrophy. Skeletal overgrowth can be severe and rapidly progressive with the development of bizarre, distorting, irregular calcified overgrowth in the tubular bones of the limbs, the skull and vertebral bodies. Cerebriform connective tissue nevi (CCTN) can occur anywhere on the body and usually develop later in childhood. Vascular malformations and linear epidermal nevi occur in the first months of life and generally stabilize with time. Adipose dysregulation and vascular malformations are noted in infancy. Neurological manifestations include intellectual deficit, sinus thrombosis and intracranial lesions. Complications include hemimegalencephaly, bullous pulmonary disease, pulmonary embolism (PE) and deep vein thrombosis (DVT). Tumors are mainly benign but rarely malignant tumours (such as papillary adenocarcinoma of the testis, meningioma and cystadenoma of the ovaries) have been reported.

Sturge-Weber syndrome (SWS)

Sturge-Weber syndrome (SWS) is a rare congenital neurocutaneous disorder characterised by facial capillary malformations and/or cerebral and ocular ipsilateral vascular malformations that result in variable degrees of ocular and neurological anomalies. The facial capillary malformation (classically referred to as angioma) is a port-wine stain (PWS) that is generally present at birth and located on the forehead or upper eyelid on one or both sides of the face. Sometimes, the PWS may also cover the maxillary and mandibular areas of the face and in some cases may extend to the trunk and limbs. Soft tissue and bony hypertrophy can be associated with a developing PWS that can lead to vision, hearing, swallowing, and speaking problems. In rare cases, patients may not present with PWS. Eye involvement can occur at anytime but is generally observed during infancy and young adulthood. More than 50% of patients develop glaucoma on the same side of the face as the PWS that can lead to optic atrophy and blindness. Cerebral vascular malformations are also present. Infants typically present in the first year of life with leptomeningeal angiomatosis, responsible for the occurrence of focal or complex partial seizures, early-handedness, and visual gaze preference. Migraines and stroke-like episodes are also very common. With the progression of the disease, and depending on the severity of seizures, patients may develop hemiparesis, hemiplegia, and variable degrees of intellectual disability. Less common aspects include an increased risk of growth hormone deficiency.

Epidermal nevus syndrome (ENS)

Epidermal nevus syndrome (ENS) is a rare congenitally acquired syndrome, characterized by the presence of epidermal nevi in association with various developmental abnormalities of the skin, eyes, nervous, skeletal, cardiovascular and urogenital systems. Epidermal nevi are developmental disorders characterized by hyperplasia of epidermal structures in a circumscribed area of the skin. Most are present at birth, occur sporadically and affect both sexes. All well-defined ENS are lethal gene syndromes, except nevus comedonicus syndrome. About 50% of the patients have neurological abnormalities that include mental retardation and epilepsy, spastic paresis, cerebral vascular malformations, cortical atrophy, lateral ventricle enlargement. About one third of the patients may have ocular abnormalities such as colobomas of the eyelid, iris and retina, conjuctival lipodermoids and choristomas, cortical blindness, micro-, macro- or anophthalmia, corneal opacities and cataracts. Skeletal abnormalities and many other non-cutaneous abnormalities may be present.

Phakomatosis pigmentokeratotica (PPK)

Phakomatosis pigmentokeratotica (PPK) is a very rare epidermal nevus disorder characterized by the association of speckled lentiginous nevi with epidermal sebaceous nevi, and extracutaneous anomalies.

Hypomelanosis of Ito

Hypomelanosis of Ito (HI) is a multisystemic neurocutaneous condition with hypopigmented skin lesions along the Blaschko lines. It is causally heterogeneous and, with the exception of the pigmentary skin anomalies that are by definition mandatory for recognition of the condition, the phenotypic presentation is very variable. The skin phenotype is characterized by unusual unilateral or bilateral cutaneous macular hypopigmented whorls, streaks and patches, corresponding to the lines of Blaschko, that usually develop within the first two years of life. Neurological, skeletal and ocular symptoms have also been reported. Anomalies of the central nervous system may include intellectual deficit, motor retardation, seizures, microcephaly, macrocephaly and hypotonia. Ophthalmological abnormalities consist of strabismus, cataracts, nystagmus and retinal degeneration. Skeletal defects include short stature, facial and limb asymmetry, tooth abnormalities, pectus carinatum or excavatum, scoliosis, and finger anomalies. Cystic renal changes have been described in rare cases.

Megalencephaly-capillary malformation-polymicrogyria syndrome

Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) is a polymalfomative syndrome characterized by cutaneous capillary malformations, megalencephaly, cortical brain malformations (most distinctively polymicrogyria), abnormalities of somatic growth with body and brain asymmetry, developmental delay, and characteristic facial dysmorphism. Symptoms are usually recognizable at birth. Their severity varies widely among patients. Macrocephaly is a major clinical feature and results from megalencephaly, which sometimes progresses to hydrocephaly. Vascular lesions (not cutis marmorata as previously thought) are often scattered over the limbs, palms, soles and trunk, are frequently pink/red, and are aggravated by crying and emotions. Facial dysmorphism is observed with full cheeks, frontal bossing, and nevus flammeus of the nose and/or philtrum and upper lip. There is a delay in speech and motor skills. Patients may present neurological symptoms, mainly neonatal hypotonia, and less frequently seizures. Additional clinical manifestations include prenatal overgrowth, limb asymmetry, joint laxity, soft skin and thick subcutaneous tissue, and/or toe syndactyly. Some patients develop neoplasias (risk of tumor development estimated at 5-6%). There is also an increased risk for congenital heart defects such as tetralogy of Fallot

Cutis marmorata telangiectatica congenita (CMTC)

Cutis marmorata telangiectatica congenita (CMTC) is a congenital localized or generalized vascular anomaly characterized by a persistent cutis marmorata pattern with a marbled bluish to deep purple appearance, spider nevus-like telangiectasia, phlebectasia and, occasionally, ulceration and atrophy of the affected skin. In 90% of cases, the skin anomalies are observed at birth or shortly after birth, and may become more accentuated in the first few weeks. CMTC manifests with a localized or generalized reticulated, frequently asymmetrical, blue-violet colored vascular network in the skin. Skin changes may range from fine diffuse capillary anomalies without atrophy to atrophic or ulcerated larger purple reticulated bands. The cutaneous lesions most commonly occur on the legs, less commonly on the arms and trunk, and rarely involve the face and scalp. More than 50% of the CMTC patients present with associated cutaneous and/or extracutaneous anomalies (referred to as the macrocephaly-CMTC syndrome; see this term), most frequently body asymmetry (hypotrophy or hypertrophy of an involved extremity) and vascular lesions (capillary malformations). Other associated anomalies include neurological abnormalities (psychomotor retardation, seizures, and hypotonia), ocular anomalies (retinal detachment and congenital glaucoma; see this term), syndactyly, and macrocephaly. CMTC can also be associated with Adams-Oliver syndrome

Mucocutaneous venous malformations (VMCMs)

Mucocutaneous venous malformations (VMCMs) are hereditary vascular malformations characterized by the presence of small, multifocal, bluish-purple venous lesions involving the skin and mucosa. The multifocal venous lesions are usually small (< 2cm in diameter), and are present at birth. They are soft and usually compressible and undergo proportionate growth with age. There is significant clinical variation with respect to the size, location and number of lesions, even between affected individuals from the same family. Classically, one individual in a given family has a large lesion. Small lesions are usually asymptomatic, whereas larger lesions can cause pain and invade subcutaneous muscle. New lesions appear with time. Patients with VMCMs have normal mental and physical development.

Kasabach-Merritt syndrome (KMS)

Kasabach-Merritt syndrome (KMS), also known as hemangioma-thrombocytopenia syndrome, is a rare disorder characterized by profound thrombocytopenia, microangiopathic hemolytic anemia, and subsequent consumptive coagulopathy in association with vascular tumors, particularly kaposiform hemangioendothelioma or tufted angioma.

Congenital Melanocytic Nevus

A large, or giant, congenital melanocytic nevus (LCMN or GCMN) is a pigmented skin lesion of more than 20 cm – or 40 cm- respectively, projected adult diameter, composed of melanocytes, and presenting with an elevated risk of malignant transformation.