INTRODUCTION — Capillary malformations (port wine stains or nevus flammeus, MIM #163000) are congenital low-flow vascular malformations of dermal capillaries and postcapillary venules. They are most often isolated skin anomalies but may rarely occur as part of complex malformation syndromes. (See 'Associated syndromes' below.)
Capillary malformations are present at birth as blanchable, pink to red patches and may be located anywhere on the body, typically with a unilateral or segmental distribution that respects the midline. They should not be confused with infantile hemangiomas, common vascular tumors of infancy that only in a minority of cases are present at birth. In contrast with infantile hemangiomas, capillary malformations do not regress with time but grow in proportion to the child's growth and become thicker and darker in color during adulthood. (See "Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications".)
The pathogenesis, clinical presentation, and associated syndromes of capillary malformations will be discussed here. Laser treatment of capillary malformations is discussed separately. An overview of vascular lesions in newborns and venous malformations are also discussed separately.
●(See "Laser and light therapy for cutaneous vascular lesions", section on 'Port wine stains'.)
●(See "Vascular lesions in the newborn".)
●(See "Venous malformations".)
EPIDEMIOLOGY — In a prospective study and literature review, capillary malformations occurred in 0.1 to 2 percent of newborns without sex predilection [1]. They are generally sporadic, but familial cases have been reported [2-4].
PATHOGENESIS — The etiology and pathogenesis of capillary malformations are unknown. Several mechanisms may be involved in their development, including vascular ectasia, lack of neuronal control of blood flow, overexpression of vascular endothelial growth factor (VEGF) and VEGF receptor, and development of compensatory, collateral passageways for venous drainage [5-7].
In a genome-wide study, a specific somatic mosaic activating mutation in the GNAQ gene on chromosome 9q21,2, encoding the guanine nucleotide binding protein G-alpha-q, was found in skin samples of 12 of 13 participants with nonsyndromic port-wine stains and in skin or brain samples of 23 of 26 participants with Sturge-Weber syndrome (a rare congenital disorder characterized by facial capillary malformation and capillary-venous malformations affecting the brain and eye) but in none of 6 control subjects [8]. This mutation (c.548G→A, resulting in the p.Arg183Gln amino acid substitution) may be involved in abnormal cell proliferation through the activation of the extracellular signal-regulated kinase (ERK) pathway. (See "Sturge-Weber syndrome".)
Nonsyndromic port-wine stains may represent a late origin of the somatic GNAQ mutation in vascular endothelial cells, whereas in Sturge-Weber syndrome mutation may occur earlier during embryogenesis in progenitor cells that are precursors to a larger variety of cell types and tissues, leading to the syndromic phenotype.
Inactivating mutations in the RASA1 gene, which cause the autosomal dominant capillary malformation-arteriovenous malformation syndrome, may be involved in hereditary cases of capillary malformations without arteriovenous malformations [2,9]. The RAS gene family encodes membrane-associated proteins that are involved in the control of cell proliferation and differentiation and organization of endothelial cells into highly organized networks [10].
PATHOLOGY — Histologic examination of port wine stains reveals ectatic capillaries and postcapillary venules in the papillary and reticular dermis. The number of vessels is not increased and there is no endothelial proliferation. Later-stage lesions develop progressive fibrosis around the vessels and dilatation of the channels. Decreased nerve density has been demonstrated within affected areas [5,11].
CLINICAL FEATURES
Clinical presentation — Capillary malformations are present at birth as partially or completely blanchable pink to red patches, with unilateral or segmental distribution that respects the midline (picture 5B). Lesions are flat, painless, and the same temperature as surrounding skin.
The face is a common location, but capillary malformations can occur anywhere on the body (picture 1). On the face, they tend to follow the distribution of the trigeminal nerve branches (segments V1 [ophthalmic], V2 [maxillary], and V3 [mandibular]) (picture 5C and figure 1). It has also been suggested that the pattern of capillary malformations may correspond to areas of somatic mosaicism or follow the embryonic vasculature [12,13]. Facial lesions may extend into the mucosal surfaces of the lips and gingivae.
In most cases, capillary malformations are isolated cutaneous anomalies. However, they may be associated with other abnormalities (eg, glaucoma and occult spinal dysraphism) or be a component of complex malformation syndromes (eg, Sturge-Weber or Klippel Trenaunay syndrome). (See 'Associated abnormalities/complications' below and 'Associated syndromes' below.)
Clinical course — Capillary malformations do not regress over time, but grow proportionally with the child's growth. Untreated lesions may become thicker, darker in color (port wine), and nodular in adulthood (picture 2).
Associated abnormalities/complications
Glaucoma — In a retrospective study of 216 children with periocular capillary malformations, 18 percent had glaucoma at presentation or developed glaucoma during a median follow-up of three years [14]. Glaucoma was more common in patients with bilateral port wine stains or involvement of the upper and lower eyelids (distribution areas of V1 and V2 trigeminal branches). A higher prevalence of glaucoma of 40 to 60 percent has been reported in case series of patients with facial capillary malformations associated with Sturge-Weber syndrome [15,16]. Early-onset glaucoma occurs before age four and causes eye enlargement (buphthalmos), whereas late-onset glaucoma may be delayed until adolescence and is not associated with buphthalmos [17]. (See "Overview of glaucoma in infants and children", section on 'Secondary glaucoma'.)
In patients with facial capillary malformation and glaucoma, brain imaging studies are recommended to exclude leptomeningeal involvement and Sturge-Weber syndrome. (See "Sturge-Weber syndrome", section on 'Diagnosis'.)
Occult spinal dysraphism — The association between isolated capillary malformations located over the lumbar spine and spinal dysraphism is controversial [18-21]. However, imaging studies to rule out occult spinal dysraphism are recommended when capillary malformations occur in conjunction with other cutaneous abnormalities (eg, hypertrichosis, dermal sinus or pit, lipomas, or deviated gluteal cleft) in the midline lumbosacral area. (See "Closed spinal dysraphism: Pathogenesis and types".)
Soft tissue and bone overgrowth — Soft tissue and/or bone overgrowth are complications of capillary malformations. Maxillary bone and gingival hyperplasia, lip enlargement, and abnormal bite may occur with facial capillary malformations in the V2 distribution [22]. Overgrowth of digits or limbs also may occur with reticulated or extensive lesions localized to the limbs. [23]
Thickening and nodularity — In large case series, skin thickening or "cobblestoning" with nodular growths within the capillary malformation occurs in up to 65 percent of lesions, especially within those located on the face (picture 3) [24-26]. On histologic examination, most nodules are pyogenic granulomas (picture 4), arteriovenous malformations, or vascular ectasias [27-31]. Easy bleeding within these lesions is common.
Early treatment may prevent thickening and development of nodularity. (See "Laser and light therapy for cutaneous vascular lesions", section on 'Lesion characteristics'.)
DIAGNOSIS
Clinical — The diagnosis of capillary malformations is in most cases clinical and based upon the appearance, time of onset, and temporal evolution of the skin lesion:
●In newborns and children, blanchable pink to red patches, often with unilateral distribution and midline demarcation (picture 5A-C); in adults, red to purple plaques with "cobblestoning" and nodular growths (picture 3). Soft-tissue and bone overgrowth may be noted in children and adults. (See 'Clinical features' above.)
●Presence at birth without regression over time.
●Growth in proportion to body growth; hyperplastic changes of the skin and underlying tissues over time in untreated lesions. (See 'Clinical course' above.)
Imaging studies — Imaging studies (ultrasonography or magnetic resonance) are not routinely performed in children with capillary malformations. However, imaging studies may be necessary in the evaluation of associated syndromes including:
●In children with facial capillary malformation involving more than one trigeminal segment (figure 1) or with neurologic symptoms and in those with facial capillary malformation and glaucoma, magnetic resonance imaging (MRI) of the brain is indicated to exclude Sturge-Weber [17,32,33]. (See "Sturge-Weber syndrome", section on 'Diagnosis'.)
●In children with symptomatic capillary malformations (warm to the touch or painful), ultrasonography can identify venous varicosities associated with Klippel-Trenaunay syndrome or exclude an associated fast-flow arteriovenous malformation. (See 'Klippel-Trenaunay syndrome' below and "Klippel-Trenaunay syndrome: Clinical manifestations, diagnosis, and management" and 'Capillary malformation-arteriovenous malformation syndrome' below.)
●MRI or computed tomography to exclude occult spinal dysraphism in children with midline lumbosacral capillary malformations associated with other cutaneous abnormalities (eg, hypertrichosis, dermal sinus or pit, lipomas, or deviated gluteal cleft). (See 'Occult spinal dysraphism' above.)
DIFFERENTIAL DIAGNOSIS — The differential diagnosis of capillary malformations includes:
●Nevus simplex – Nevus simplex, also called salmon patch or stork bite, is a common birthmark occurring in up to 80 percent of newborns [1]. It is similar in appearance to capillary malformations but has more indistinct borders and is usually located in the midline. The most common locations are the glabella, upper eyelids, and nape of the neck (picture 6), but they can also be present in other locations including the forehead (picture 7), nose, upper and lower cutaneous lip, philtrum, scalp, and the upper, mid, and lower back [34]. Unlike capillary malformations, these lesions (with the exception of those located on the nape of the neck) fade spontaneously over time. (See "Vascular lesions in the newborn", section on 'Nevus simplex (macular stain)'.)
●Infantile hemangioma – In approximately one-third of cases, infantile hemangioma is present at birth as a macular telangiectatic patch similar in appearance to a capillary malformation (picture 8). Hemangiomas with this presentation often have surrounding pallor representing vasoconstriction, which can help to differentiate them from capillary malformations early on. However, in contrast with capillary malformations, hemangiomas quickly begin to develop small vascular blebs and become raised (picture 9). (See "Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications".)
●Arteriovenous malformation – Arteriovenous malformations may present as macular vascular stains (picture 10C). However, they are often warm to the touch and a thrill may be felt on palpation. Over time, arteriovenous malformations become progressively raised and develop a deep component (picture 10A-B). (See "Peripheral arteriovenous malformations".)
●Linear scleroderma – Linear scleroderma (morphea) of the face, particularly the "en coup de sabre" form, may rarely present at birth as an erythematous patch and mimic a capillary malformation (picture 11A) [35,36]. Over time, these lesions develop induration and atrophy typical of scleroderma (picture 11B). (See "Juvenile localized scleroderma".)
INDICATIONS FOR REFERRAL — Neonates presenting with a capillary malformation involving the upper and lower eyelids and the frontotemporal region (V1 and V2 segments) should be referred for ophthalmologic examination to rule out glaucoma. (See 'Glaucoma' above.)
Children with a facial capillary malformation and neurologic symptoms, particularly seizures, should be referred for neurologic examination and neuroimaging studies to exclude Sturge-Weber syndrome. (See "Sturge-Weber syndrome", section on 'Diagnosis'.)
TREATMENT — Capillary malformations may be disfiguring and a source of significant psychologic stress for patients [37]. The goals of treatment are cosmetic improvement (reduction of skin redness) and prevention of complications (eg, thickening, nodularity, or bleeding) [38-41].
Pulsed dye laser (PDL) therapy is considered the standard of care for the treatment of capillary malformations [42]. It is based on the concept of selective photothermolysis with oxyhemoglobin as the target [43]. PDL treatment irreversibly damages the capillary vessel wall with minimal damage to the overlying epidermis, which leads to lightening of the port wine stain without scarring [44].
PDL therapy for capillary malformations is reviewed in detail separately. (See "Laser and light therapy for cutaneous vascular lesions", section on 'Port wine stains'.)
ASSOCIATED SYNDROMES
Sturge-Weber syndrome — Sturge-Weber syndrome (SWS) is a rare congenital disorder characterized by the classic triad of facial port wine stain, leptomeningeal angiomatosis, and ocular involvement. The capillary malformation associated with SWS usually occurs in the distribution area of the ophthalmic and/or maxillary branch (segments V1/V2) of the trigeminal nerve (figure 1), involves both the upper and lower eyelids, and is often bilateral [45]. The discovery of the somatic mutation in GNAQ associated with SWS has raised the hypothesis of somatic mosaicism in SWS [8]. In a multicenter prospective study of 66 infants with upper facial port wine stains larger than 1 cm2 located in the ophthalmic division (figure 1) of trigeminal nerve distribution, 11 (17 percent) were diagnosed with SWS [12]. Hemifacial and median (including median linear) distribution pattern were associated with a high risk of SWS.
The clinical features, diagnosis, and treatment of Sturge-Weber syndrome are discussed in detail separately. (See "Sturge-Weber syndrome".)
Klippel-Trenaunay syndrome — Capillary malformations, venous and lymphatic malformations, and soft tissue and bone hypertrophy involving a limb are prominent features of Klippel-Trenaunay syndrome (KTS) [46,47]. The lower limbs, sometimes with extension to the trunk, are more frequently involved than the upper limbs.
The capillary malformations are present at birth as extensive, geographic patches located on the trunk or extremity (picture 12). Limb hypertrophy, resulting from soft tissue and bone overgrowth and underlying lymphatic abnormalities, may be apparent at birth or may develop later and progress until the end of puberty (picture 13).
The diagnosis and management of Klippel-Trenaunay syndrome are discussed in detail separately. (See "Klippel-Trenaunay syndrome: Clinical manifestations, diagnosis, and management".)
Parkes-Weber syndrome — Parkes-Weber syndrome is characterized by a large capillary malformation on an extremity, soft tissue and bone hypertrophy of the affected limb, and multiple, microscopic, fast-flow arteriovenous shunts. The capillary malformation of Parkes-Weber syndrome is indistinguishable from the port wine stain seen in KTS. Ultrasonography, MRI, and magnetic resonance arteriography are helpful in differentiating Parkes-Weber syndrome from KTS.
Patients with Parkes-Weber syndrome have progressive overgrowth of the affected limb and complications related to the arteriovenous shunts, including ulcerations and high-output cardiac failure, especially in the neonatal period.
Servelle-Martorell syndrome — Servelle-Martorell syndrome is a rare congenital angiodysplastic disease [48]. It manifests with capillary malformations and varicosities similar to KTS, but is associated with progressive limb hypotrophy rather than overgrowth.
Proteus syndrome — Proteus syndrome is an extremely rare disorder characterized by asymmetric and disproportionate overgrowth of body parts (picture 14). Mosaicism for a somatic activating mutation in the AKT1 oncogene is thought to be the cause of Proteus syndrome.
Cutaneous findings are present in approximately 40 percent of neonates and include capillary, lymphatic, or venous malformations; epidermal nevi; connective tissue nevi; lipomas; café-au-lait macules; and hypertrichotic patches [49,50]. The vascular malformations are usually extensive, covering a large portion of the body, and may be associated with visceral vascular malformations. Overgrowth is evident at birth in approximately 20 percent of cases and is asymmetric, disproportionate, and progressive. It may involve many tissues including bone, cartilage, muscle, and connective tissue.
The diagnosis and management of Proteus syndrome are discussed separately. (See "PTEN hamartoma tumor syndromes, including Cowden syndrome", section on 'Proteus-like syndrome'.)
CLOVES syndrome — Congenital lipomatous overgrowth, vascular malformations, epidermal nevi, spinal/skeletal anomalies/scoliosis (CLOVES) syndrome is a very rare congenital disorder caused by somatic mosaic activating mutations in the PIK3CA gene [51-53]. (See "Klippel-Trenaunay syndrome: Clinical manifestations, diagnosis, and management", section on 'CLOVES syndrome'.)
Bannayan-Riley-Ruvalcaba syndrome — Bannayan-Riley-Ruvalcaba syndrome, which is incorporated into Cowden syndrome-1 (MIM #158350), is an autosomal dominant disorder caused by mutations in the tumor suppressor gene PTEN [54]. Cutaneous features include capillary, venous, and lymphatic malformations as well as lipomas and pigmented macules on the genitalia. Associated findings include macrocephaly, pseudopapilledema, intellectual disability, and juvenile intestinal polyposis.
Cowden syndrome-1 is discussed separately. (See "PTEN hamartoma tumor syndromes, including Cowden syndrome", section on 'Bannayan-Riley-Ruvalcaba syndrome'.)
Capillary malformation-arteriovenous malformation syndrome — Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is an autosomal dominant disorder caused by mutations in the RASA1 gene [9]. RASA1 encodes the protein involved in the control of cell proliferation and differentiation and organization of endothelial cells into highly organized networks [10].
CM-AVM syndrome is characterized by atypical cutaneous capillary malformations in conjunction with an AVM. The AVM can be localized or diffuse and can be located in the soft tissues, muscles, bones, brain, or spine [55,56].
The capillary malformations are usually multiple, round to oval, pink-red or tan patches of 1 to 2 cm in size scattered randomly on the body. New lesions may continue to appear throughout childhood. A high flow murmur can usually be detected over the lesions with a hand-held Doppler device [57].
Doppler ultrasonography and/or MRI and magnetic resonance arteriography of clinically involved areas and brain are needed to evaluate the extension of AVM.
Macrocephaly-capillary malformation syndrome — Macrocephaly-capillary malformation (M-CM) syndrome (previously named macrocephaly-cutis marmorata telangiectatica congenita) is a genetic syndrome characterized by an enlarged head circumference and patchy, reticular capillary malformations [58-60]. It is caused by mutations in the PIK3CA gene, leading to gain of function and activation of the PI3K-AKT pathway, which is involved in cell growth, proliferation, survival, and apoptosis [61,62].
The diagnosis is based upon the presence of two major clinical criteria and at least two minor criteria.
Major criteria are:
●Macrocephaly
●Capillary malformation
Minor criteria are:
●Asymmetry or overgrowth
●Developmental delay
●Hypotonia
●Syndactyly or polydactyly
●Frontal bossing
●Hydrocephalus
●Connective tissue abnormalities such as joint hypermobility or hyperelastic skin
●Midline facial nevus simplex
The capillary malformations are usually reticulated and widespread on the trunk and extremities. Cardiac abnormalities including aortic coarctation have also been described [63,64]. Neuroimaging findings include white matter abnormalities, ventriculomegaly, cerebral asymmetry, cortical dysplasia, polymicrogyria-like changes, and cerebellar tonsil herniation [65].
Microcephaly-capillary malformation syndrome — Microcephaly-capillary malformation (MICCAP, MIM #614261) is an autosomal recessive syndrome due to mutations in the STAMBP gene on chromosome 2p13.1, encoding a deubiquitinating enzyme [66-69]. It presents with:
●Severe progressive microcephaly
●Diffuse small capillary malformations of the skin
●Profound global developmental delay
●Severe spastic quadriparesis
●Neonatal-onset intractable epilepsy
●Hypoplastic distal phalanges
●Poor growth
The capillary malformations range in size from 2 to 15 mm and are scattered on the trunk, extremities, and head. Minor heart malformations, including small atrial and ventricular septal defects, have also been reported [67]. Neuroimaging findings include diffusely reduced number of gyri with shallow sulci consistent with a severe simplified gyral pattern, and moderately enlarged extra-axial space [67].
Beckwith-Wiedemann syndrome — Beckwith-Wiedemann syndrome is a congenital overgrowth syndrome with major features including anterior abdominal wall defects, macroglossia, gigantism, and a propensity to develop specific tumors (hepatoblastoma, Wilms tumour, neuroblastoma, and rhabdomyosarcoma) [70,71]. Infants have centrofacial capillary malformations similar to nevus simplex in the majority of cases. Vascular lesions may extend to the upper eyelids, upper lip, and nose. Characteristic-associated findings are an anterior ear lobe crease and posterior helical ear pits.
Beckwith-Wiedemann syndrome is discussed separately. (See "Beckwith-Wiedemann syndrome".)
Phakomatosis pigmentovascularis — Phakomatosis pigmentovascularis is a syndrome characterized by the association of a widespread capillary malformation with pigmented lesions including dermal melanocytosis, nevus spilus, mosaic hyperpigmentation, and epidermal nevus. Nevus anemicus and café-au-lait spots can be associated findings. Extracutaneous findings include visceral, muscular, neurologic, or ocular abnormalities.
Five types of phakomatosis pigmentovascularis have been identified based upon the type of pigmented lesion associated with the capillary malformation; for each type, subtype "a" denotes absence and subtype "b" presence of extracutaneous findings (table 1) [72-74].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Vascular anomalies".)
SUMMARY AND RECOMMENDATIONS
●Capillary malformations (port wine stains or nevus flammeus) are low-flow vascular malformations of dermal capillaries and postcapillary venules. (See 'Introduction' above.)
●Characteristic clinical features include blanchable pink to red patches located anywhere on the body (picture 1), typically with a unilateral or segmental distribution that respects the midline (picture 5A-C). On the face, capillary malformations tend to follow the distribution of the trigeminal nerve branches (picture 5C and figure 1). (See 'Clinical presentation' above.)
●Lesions do not regress and, if left untreated, may become thicker, darker in color (port wine), and nodular in adulthood (picture 3). (See 'Clinical course' above.)
●The diagnosis of capillary malformations can be made with a history and examination in patients with characteristic clinical features (picture 5A-C). Imaging studies (ultrasonography or magnetic resonance) may be necessary in the evaluation of associated syndromes or abnormalities. (See 'Diagnosis' above.)
●The differential diagnosis of capillary malformations includes nevus simplex (salmon patch or stork bite) (picture 7), infantile hemangioma (picture 9), arteriovenous malformation (picture 10A-C), and linear scleroderma (picture 11A-B).
●Pulsed dye laser (PDL) therapy is considered the standard of care for the treatment of capillary malformations. PDL therapy for capillary malformations is discussed separately. (See "Laser and light therapy for cutaneous vascular lesions", section on 'Port wine stains'.)
●In most cases, capillary malformations are isolated cutaneous anomalies. However, they may be associated with other abnormalities (eg, glaucoma and occult spinal dysraphism) or be a component of complex malformation syndromes (eg, Sturge-Weber or Klippel Trenaunay syndrome). (See 'Associated abnormalities/complications' above and 'Associated syndromes' above.)
1 : A prospective study of cutaneous findings in newborns in the United States: correlation with race, ethnicity, and gestational status using updated classification and nomenclature.
2 : RASA1 mutations may cause hereditary capillary malformations without arteriovenous malformations.
3 : Locus for susceptibility for familial capillary malformation ('port-wine stain') maps to 5q.
4 : A locus for hereditary capillary malformations mapped on chromosome 5q.
5 : Port-wine stains. A disease of altered neural modulation of blood vessels?
6 : The expression of vascular endothelial growth factor and its receptors in port-wine stains.
7 : Sturge-weber syndrome: a unified pathophysiologic mechanism.
8 : Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ.
9 : Capillary malformation-arteriovenous malformation, a new clinical and genetic disorder caused by RASA1 mutations.
10 : Vascular system defects and neuronal apoptosis in mice lacking ras GTPase-activating protein.
11 : Confocal microscopy study of neurovascular distribution in facial port wine stains (capillary malformation).
12 : A prospective study of risk for Sturge-Weber syndrome in children with upper facial port-wine stain.
13 : New vascular classification of port-wine stains: improving prediction of Sturge-Weber risk.
14 : Periocular port wine stain: the great ormond street hospital experience.
15 : Port-wine vascular malformations and glaucoma risk in Sturge-Weber syndrome.
16 : Sturge-Weber syndrome and dermatomal facial port-wine stains: incidence, association with glaucoma, and pulsed tunable dye laser treatment effectiveness.
17 : Facial port-wine stains - clinical stratification and risks of neuro-ocular involvement.
18 : Skin markers of occult spinal dysraphism in children: a review of 54 cases.
19 : Sacral nevus flammeus simplex: the role of imaging.
20 : Butterfly-shaped mark: a variant form of nevus flammeus simplex.
21 : Sacral medial telangiectatic vascular nevus: a study of 43 children.
22 : Orodental manifestations of facial port-wine stains.
23 : Vascular malformations: Part I.
24 : Demographic study of port wine stain patients attending a laser clinic: family history, prevalence of naevus anaemicus and results of prior treatment.
25 : The medical necessity of evaluation and treatment of port-wine stains.
26 : Thickening and nodules in port-wine stains.
27 : Vascular tumors arising in port-wine stains: two cases of pyogenic granuloma and a case of acquired tufted angioma.
28 : Pyogenic granuloma (lobular capillary hemangioma) within port-wine stains.
29 : Pyogenic granuloma arising as a complication of 595 nm tunable pulsed dye laser treatment of port-wine stains: report of four cases.
30 : Nodules arising within port-wine stains: a clinicopathologic study of 31 cases.
31 : Acquired tufted angioma.
32 : Sturge-Weber syndrome in patients with facial port-wine stain.
33 : Bilateral facial capillary malformation associated with eye and brain abnormalities.
34 : Nevus simplex: a reconsideration of nomenclature, sites of involvement, and disease associations.
35 : Early localized morphea mimicking an acquired port-wine stain.
36 : Congenital localized scleroderma.
37 : Psychological disabilities amongst patients with port wine stains.
38 : The medical necessity for treatment of port-wine stains.
39 : The necessity for treatment of childhood port-wine stains.
40 : Pulsed dye laser therapy for port-wine stains in children: psychosocial and ethical issues.
41 : Long-term psychological impact and perceived efficacy of pulsed-dye laser therapy for patients with port-wine stains.
42 : Lasers or light sources for treating port-wine stains.
43 : Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation.
44 : Treatment of pulsed dye laser-resistant port wine stain birthmarks.
45 : Location of port-wine stains and the likelihood of ophthalmic and/or central nervous system complications.
46 : Vascular malformations. Part II: associated syndromes.
47 : Vascular Anomalies Classification: Recommendations From the International Society for the Study of Vascular Anomalies.
48 : Congenital vascular malformation associated with multiple cranial, vertebral and upper limb skeletal abnormalities.
49 : Reassessment of the Proteus syndrome literature: application of diagnostic criteria to published cases.
50 : Hypertrichotic patches as a mosaic manifestation of Proteus syndrome.
51 : Newly delineated syndrome of congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome) in seven patients.
52 : Characterization of a distinct syndrome that associates complex truncal overgrowth, vascular, and acral anomalies: a descriptive study of 18 cases of CLOVES syndrome.
53 : Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome.
54 : Germline mutations in PTEN are present in Bannayan-Zonana syndrome.
55 : A novel association between RASA1 mutations and spinal arteriovenous anomalies.
56 : RASA1 mutations and associated phenotypes in 68 families with capillary malformation-arteriovenous malformation.
57 : Parkes Weber syndrome, vein of Galen aneurysmal malformation, and other fast-flow vascular anomalies are caused by RASA1 mutations.
58 : The misnomer "macrocephaly-cutis marmorata telangiectatica congenita syndrome": report of 12 new cases and support for revising the name to macrocephaly-capillary malformations.
59 : Macrocephaly-capillary malformation: Analysis of 13 patients and review of the diagnostic criteria.
60 : Accurately renaming macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC) as macrocephaly-capillary malformation (M-CM).
61 : De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes.
62 : Megalencephaly syndromes and activating mutations in the PI3K-AKT pathway: MPPH and MCAP.
63 : Macrocephaly-cutis marmorata telangiectatica congenita: report of six new patients and a review.
64 : Macrocephaly-capillary malformation: a report of three cases and review of the literature.
65 : Neuroimaging findings in macrocephaly-capillary malformation: a longitudinal study of 17 patients.
66 : Mutations in STAMBP, encoding a deubiquitinating enzyme, cause microcephaly-capillary malformation syndrome.
67 : The microcephaly-capillary malformation syndrome.
68 : Multiple capillary skin malformations, epilepsy, microcephaly, mental retardation, hypoplasia of the distal phalanges: report of a new case and further delineation of a new syndrome.
69 : A new syndrome with multiple capillary malformations, intractable seizures, and brain and limb anomalies.
70 : Beckwith-Wiedemann syndrome.
71 : Risk of cancer during the first four years of life in children from The Beckwith-Wiedemann Syndrome Registry.
72 : Phakomatosis pigmentovascularis: Clinical findings in 15 patients and review of the literature.
73 : Large aberrant Mongolian spots coexisting with cutis marmorata telangiectatica congenita (phacomatosis pigmentovascularis type V or phacomatosis cesiomarmorata).
74 : Phacomatosis pigmentovascularis revisited and reclassified.