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Becker's Nevus Syndrome

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 Review Article

Becker’s Nevus Syndrome

Maria Elena Cucuzza1,
Sara Paternò1,
Daniele Attardo1 Andrea D. Praticò1,2 Stefano Catanzaro1
Agata Polizzi3 Carmelo Schepis4 Francesco Lacarrubba5 Giuseppe Micali5 Anna Elisa Verzì5
Concetta Pirrone6 Elena Commodari6 Antonio Zanghì7 Stefania Salafia8 Elena R. Praticò9
Ignacio Pascual-Castroviejo10 Martino Ruggieri1

1 Unit of Rare Diseases of the Nervous System in Childhood, Department of Address for correspondence Andrea D. Praticò, MD, PhD, Unit of Rare
Clinical and Experimental Medicine, Section of Pediatrics and Child Diseases of the Nervous System in Childhood, Department of Clinical
Neurospychiatry, University of Catania, Catania, Italy and Experimental Medicine, Section of Pediatrics and Child
2 Maurice Woh Clinical Neuroscience Institute, King’s College Neuropsychiatry, University of Catania, AOU “Policlinico-Vittorio
London, London, United Kingdom Emanuele,” Presidio “G. Rodolico,” Via S. Sofia, 78, 95124, Catania,
3 Instiute of Neurological Science, National Research Council, Catania, Italy Italy (e-mail: andrea.pratico@unict.it).
4 Unit of Dermatology, Oasi Research Institute - IRCCS, Troina, Enna, Italy
5 Dermatology Clinic, University of Catania, Catania, Italy
6 Section of Psychology, Department of Educational Sciences
University of Catania, Catania, Italy
7 Department of Medical and Surgical Sciences and Advanced
Technology “G.F. Ingrassia,” University of Catania, Catania, Italy

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8 Unit of Pediatrics, Lentini Hospital, Lentini, Italy
9 Unit of Pediatrics, Carpi Hospital, Carpi, Italy
10 Servicio de Neurología, Hospital Universitario La Paz, Madrid, España

J Pediatr Neurol

Abstract The simultaneous occurrence of a patch of light or dark brown hyperpigmentation with
hypertrichosis (Becker’s nevus) together with (usually ipsilateral) soft tissues hypoplasia
(especially breast, in women) and underlying skeletal anomalies (i.e., vertebral hypoplasia,
scoliosis, pectus carinatum or excavatum) represents the Becker’s nevus syndrome (BNS)
phenotype. It was first described (as a single cutaneous lesion) by Becker in 1949 and then
associated with the surrounding musculoskeletal disorders. The syndrome has also been
reported as pigmentary hairy epidermal nevus syndrome. Less than 100 cases have been
reported in the literature, with a slightly higher incidence in females and only few familiar
Keywords cases: paradominant postzygotic mutations and/or an androgen-dependent hyperactiva-
► Becker’s nevus tion have been reported as the causes of the diseases.
► hyperpigmentation The extracutaneous lesions are congenital and nonprogressive, and the natural history of
► hypertrichosis the Becker’s nevus is the same as that of isolated nevi: in prepubertal boys, the pigmentation
► soft tissues may be less intense and the hairiness may be absent or mild, as occurs in women, whereas in
hypoplasia men, there is an increase of hairiness after puberty. The treatment is essentially cosmetic,
► skeletal abnormalities and potential therapeutic options include electrolysis, waxing, makeup, or laser.

Introduction or dark brown hyperpigmentation with a sharply outlined

Becker’s nevus syndrome (BNS) is characterized by the
simultaneous occurrence of a circumscribed patch of light


Both authors contributed equally to the manuscript.
but irregular border (resolving into small spots reminiscent
of an archipelago) and hypertrichosis (the so-called Becker’s
nevus [BN]).1,2 It is associated with unilateral hypoplasia of
one or more of the following: breast, areola and/or nipple,
underlying musculature (mostly the shoulder girdle),

received Issue Theme Rare Neurocutaneous Copyright © by Georg Thieme Verlag KG, DOI https://doi.org/
February 5, 2018 Disorders: Update and State of Art; Guest Stuttgart · New York 10.1055/s-0038-1667168.
accepted after revision Editors, Martino Ruggieri, BA, MD, PhD, ISSN 1304-2580.
May 21, 2018 Andrea Praticò, MD, PhD, and Giuseppe
Micali, MD
Becker’s Nevus Syndrome Cucuzza et al.
underlying adipose tissue (lipoatrophy) and limb (usually
the arm); moreover, underlying skeletal anomalies may be
present, including vertebral defects and scoliosis, fused or
accessory cervical ribs, pectus excavatum or carinatum, and
internal tibial torsion.3–5
All of these anomalies tend to show a regional correspon-
dence to the nevus and are mostly ipsilateral.2 An isolated
case with the involvement of the contralateral side has also
been reported.6,7
Historical Background and Eponyms
Much later than other neurocutaneous disorders,8–12 BN in an
epidermal cutaneous hamartoma was first described in 1949
by Becker.2 He reported on two young men with acquired
melanosis and hypertrichosis in a unilateral distribution.
In the past, various authors have associated BN with other
musculoskeletal disorders such as unilateral hypoplasia of
the breast or scoliosis.13–15 However, this association did not
receive much attention until 1995 when the term “pigmen-
tary hairy epidermal nevus syndrome” was proposed by
Happle. Later, Happle and Koopman described BNS for the
simultaneous presence of BN within certain subcutaneous,
muscular, and skeletal defects.3–7
Incidence and Prevalence
Different from other (more common) neurocutaneous
syndromes,13–40 BNS is very rare. From 2004 to 2016, approxi-
mately 73 cases have been reported in the literature with a
female:male ratio of 1.5:1.0.16,17 The reason has been partially
explained by the fact that the most frequently reported
anomaly, hypoplasia of the breast, is much evident in females.3
Skin Manifestations
The cutaneous anomaly, which is also known as “pigmentary
hairy epidermal nevus,” constitutes the hallmark of the
syndrome, although it mostly occurs as an isolated skin
abnormality.4,41 It can be categorized as a particular type
of androgen-dependent organoid epidermal nevus, which
often involves the thorax or the scapular region but may
affect any area of the body, usually in a mosaic (checker-
board) (►Fig. 1) pattern.3,5
Clinically, BN appears with two different morphological
clinical patterns: as a single irregular macular hyperpigmen-
tation or as multiple hyperpigmented macules arranged in a
checkerboard pattern.42–44 The nevus is characterized by the
presence of light or dark brown maculae with a sharply
outlined but irregular and bizarre borders that resolve into
small spots reminiscent of an archipelago (►Fig. 1). Besides
the typical clinical presentation of BN, a nonhairy BN has also
been observed.45,46 BN mainly appears in the first
and second decades of life, sometimes after sun exposure,
and it is rarely described at birth.42 Dermoscopy, a non-
invasive diagnostic technique that is widely used in derma-
tology,47 may be useful for the differential diagnosis with
congenital melanocytic nevi.48 Most lesions are unilaterally
Journal of Pediatric Neurology
Fig. 1 Becker nevus syndrome: pigmentary hairy nevus of the thorax
arranged in a checkerboard pattern.
localized to the upper quadrant of the chest and shoulder, but
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they can be found on any area of the body including the
forehead, face, neck, lower, trunk, extremities, and but-
tocks.6,49–51 After its appearance, BN may grow for a year
or two but then remains fixed in size. In the course of time,
pigmentation can fade however.49
A systematic involvement that may be either unilateral or
bilateral has likewise been described.20 Involvement of the
head may result in asymmetric hair growth within the nevus,
asymmetric growth of beard, or pronounced acne lesions
within the nevus.3 Cases with localized scleroderma have
been also reported.52–56
Given the increased number of androgen receptors and
androgen receptor messenger RNA (mRNA), compared with
unaffected skin, the “full-blown” picture of BN has been
reported exclusively in adolescent or adult men.3,5,24–27 The
intralesional presence of acne lesions and the occurrence of
BN in a patient with an accessory scrotum further reflect the
pathogenic role of androgens in this disorder.3,57 In women
and prepubertal boys, the pigmentation is less intense, and
hairiness is absent or only mild.4
Recently, Sheng et al investigated the clinical–pathologi-
cal features and immunohistochemical alterations in 60
newly diagnosed BN. Histopathological examination after
comparison with previous studies revealed that the epider-
mis changes (elongated and fused rete ridges, keratotic
plugging, and basal pigmentation) were similar except
acanthosis, but dermal alterations (mild perivascular lym-
phohistiocytic infiltration, fibrosis, and smooth muscle and
sebaceous hyperplasia) were more common.57 An increased
number of melanocytes was found, but their pathogenic role
remains to be further investigated. Furthermore, this study
demonstrated a hyperproliferation of keratinocytes, arrector
pili muscle and dermal nerve fibers, slight epidermal
acanthosis and regular elongation of rete ridges, variable
hyperkeratosis, and acanthosis. Also, the basal cell layer
presents hyperpigmentation, and melanophages are present
in the papillary dermis.2,58 The erector pili muscles are
increased in number and size, often resulting in histopatho-
logical appearance indistinguishable from smooth muscle
 Becker’s Nevus Syndrome Cucuzza et al.

hamartomas. Neither epidermis nor dermis contains any

increase or aggregation of melanocytes.17

Other Cutaneous Anomalies

To date, various cutaneous anomalies have also been
reported to present with BN. These include patchy hypopla-
sia of ipsilateral extramammary fatty tissue, hypoplasia of
the contralateral labium minus, an accessory scrotum, sparse
hair of the ipsilateral axilla, patchy cutaneous hypoplasia of
the ipsilateral temporal region, and supernumerary nipples.3
Other cutaneous anomalies have been associated with BN,
including sebaceous nevus, tinea versicolor, lichen planus,
smooth muscle hamartoma, nevus depigmentosus, hypohi-
drosis, prurigo nodularis with eczematous dermatitis, gran-
uloma annulare, squamous cell carcinoma in situ, malignant Fig. 2 Left mammillary hypoplasia in a woman affected by Becker’s
melanoma, acanthosis nigricans, lymphangioma, and multi- nevus syndrome.
ple leiomyoma cutis.58,59 Some other authors also describe
children with BN and other pigmentary anomalies, such as

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congenital melanocytic nevus, Sutton’s nevi, and hypomela-
notic congenital patch, or with café au lait spots and salmon
patch (►Table 1).5,6 Other authors have described a single
case report of BN with bilateral skin involvment.59,60
Table 1 Extracutaneous anomalies in Becker’s nevus syndrome
Tissue Associated anomalies
Soft tissues Ipsilateral hypoplasia of the breast and/
and muscles or areola and/or nipple
Contralateral breast hypoplasia
Supernumerary nipples
Ipsilateral absence or thinning of the
pectoralis major muscle
Ipsilateral hypoplasia of fatty tissue
of the trunk
Ipsilateral hypoplasia of the shoulder girdle
Asymmetry of the upper extremity
Asymmetry of the lower extremity
Ipsilateral hypoplasia of the temporal
region
Hypoplasia of the ipsilateral axilla
Umbilical hernia
Hypoplasia of the contralateral
labium minus
Accessory scrotum
Bones Scoliosis
Spina bifida occulta
Pectus excavatum/carinatum
Fused accessory cervical ribs
Ipsilateral fused capitate and hamate bones
Asymmetry of the scapulae
Bilateral internal tibial torsion
Unilateral Hypoplasia of the Breast
In affected women, this is the most frequently reported
anomaly associated with BN (►Fig. 2), but it has also been
reported in men, usually in the form of hypoplastic areola.3,4
Characteristically, the anomalies are found ipsilateral to the
nevus, but few patients present a contralateral side involve-
ment.6 In female patients, it may involve the entire breast
including the fatty tissue or only the nipple and areola.3
Maxillofacial Abnormalities
“Hemimaxillary enlargement, asymmetry of the face, tooth
abnormalities, and skin findings” (HATS) is a rare develop-
mental disorder involving the first and second branchial
arches. Physical manifestations may present at birth or
during early childhood. Among the characteristic cutaneous
manifestations of HATS syndrome, BN is the most common.61
Ipsilateral segmental odontomaxillary dysplasia has been
also reported, together with the ipsilateral absence of the
right maxillary lateral incisor and canine teeth, facial asym-
metry, and polyostotic fibrous dysplasia of the right maxillae
and mandible. Because of the closer regional relationship
between the cutaneous and extracutaneous lesions, the
authors assumed a common origin of the lesions.2,3
Musculoskeletal Anomalies
As in other neurocutaneous disorders,62 bone and muscle
anomalies are frequently observed. They can include scolio-
sis, vertebral defects (including hemivertebrae, cleft verteb-
rae, and spina bifida occulta), fused or accessory cervical ribs,
pectus excavatum or carinatum, asymmetry of scapulae,
short limb or other forms of limb asymmetry, bilateral
internal tibial torsion, ipsilateral hypoplasia of the shoulder
girdle (including absence of the pectoralis major muscle),
hypoplasia of the sternocleidomastoid muscle, and umbilical
hernia.3,4,63,64

Journal of Pediatric Neurology

Becker’s Nevus Syndrome Cucuzza et al.
Miscellaneous Findings
Bilateral congenital cataract has been reported in one woman
so far. Many neurologic diseases have been associated with
BN, including neurofibromatosis type I, muscle dystrophy,
partial epilepsy, and hyposmia, as well as several
endocrinopathies.6,65–78 Nervous system malformation
(megalencephaly, Arnold–Chiari malformation, and Dandy–
Walker’s syndrome) can also be associated with BN.79–87
Natural History
The associated extracutaneous lesions are congenital and
thus nonprogressive. The natural history of BN within the
syndromic constellation is the same as in the isolated nevi: in
prepubertal boys, the pigmentation may be less intense and
the hairiness may be absent or mild, as occurs in women,
whereas in men, there is an increase of hairiness after
puberty.
Pathogenesis and Molecular Genetics
The exact etiology of BN remains unclear. There are two main
hypotheses concerning this disorder. The first, genetic,
associates the syndrome with the occurrence of a postzygotic
autosomal fatal mutation that can “survive” only in a mosaic
pattern: it is corroborated by the fact that the majority of
cases are sporadic and familiar grouping is very rare, similar
to what happens in other neurocutaneous pheno-
types.38,88–93 The second hypothesis states that BNS is a
hormone-dependent disorder; this theory is based on the
increased number of androgen receptors in the affected
areas: for this reason, the appearance of lesions is more
frequent in puberty, and alteration such as hypertrichosis
and acneiform eruptions are restricted to the regions.94
As reported above, BN is an androgen-sensitive lesion. It
presents with increased androgen receptor mRNA and
androgen receptors, as well as increased receptor positivity
in basal keratinocytes and dermal fibroblasts. BN’s androgen
receptor activity seems to explain the time of onset (peri-
pubertal period) as well as its associated findings involving
papillomatosis, acanthosis, acne, hirsutism, and breast
hypoplasia.95,96
Becker’s nevus and mammary hypoplasia can be
explained as hormone-dependent developmental abnorm-
alities caused by disturbances of receptor activity.2,54 The
development of breast, areola, and nipples is essentially
estrogen-dependent in both sexes: hypoplasia of these
structures could be caused by an excess of androgen recep-
tors in the region of the nevus counteracting the effect of
estrogens.2 The associated musculoskeletal anomalies, how-
ever, are difficult to explain solely by this pathogenic
mechanism and could be better explained by regional
(mosaic) correspondence between the area of the nevus
and the associated anomaly.2,3
Paradominant patterns of inheritance: BNS might repre-
sent a paradominant phenomenon.3 The disorder would
become apparent when a postzygotic mutation occurred in
Journal of Pediatric Neurology
the developing embryo on the basis of the following: (1) the
sporadic occurrence of isolated BN in most but not all cases;
in fact there are few families with several affected mem-
bers2; (2) Mendelian inheritance patterns do not explain why
the disease always occurs in mosaic patterns; (3) mosaicism
for chromosomal abnormalities has been documented in
fibroblasts derived from a BN in one sporadic case60; and
(4) the familial occurrence of BNS with a father and his eldest
son both affected by BN and scoliosis, with another son and a
daughter having isolated BN.61 The sporadic occurrence and
asymmetrical distribution of most BNs suggest cutaneous
mosaicism. Few cases of familial presentations have been
reported: it was found in 0.25% of the study population in a
study and in 0.52% of them in another study.79 Based on the
spectrum of extracutaneous anomalies, one may assume that
the causative gene(s) is involved in the regulation of adipose
tissue distribution. Since BNS is expressed in a segmental
pattern, a lethal autosomal mutation only surviving as a
mosaic seems to be the most likely genetic explanation.15 A
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case of BN arranged in close proximity to unilateral nevoid
telangiectasia was also observed. In one patient, the BN,
arranged in a checkerboard pattern in the chest and
shoulder, was associated with a capillary malformation of
one thigh and ipsilateral buttock.94 These associations could
be taken as possible examples of twin spotting, implying
allelic loss by somatic recombination.97
The concept of paradominant inheritance implies that
both BN and BNS originate from regional loss of heterozyg-
osity occurring at an early stage of embryogenesis and
resulting in a mosaic population of homozygous cells. Recent
genetic studies have shown that a somatic recombination
occurring in early embryogenesis may result in the emer-
gence of nevi and nevus-related disorders. When ectoderm is
somehow disturbed during embryological development, dis-
orders in tissue and organ groups evolving from the ecto-
derm become prominent.98 The severity and extent of the
ectodermal involvement may be the reason for the variability
of the clinical signs and symptoms associated with BNS.
Heterozygous individuals would be, as a rule, phenotypically
normal, and the responsible mutation would, therefore, be
transmitted unperceived through many generations. Only
when loss of heterozygosity occurs in more than one indi-
vidual in the family does the familial transmission of BN
become evident.99 This would explain why BNS virtually
always occurs sporadically but may show, by way of excep-
tion, a familial aggregation.2,3
Histopathological Findings
In a recent immunohistochemical study of BN,57 nuclear Ki-67
(melanocyte differentiation antigen) stain was observed in the
basal and parabasal keratinocytes of the epidermis, hair matrix
cells and a few outermost layer cells of the outer root sheath in
the hair follicles, and some eccrine duct cells. Cytoplasmic
Melan-A expression was seen in the basal melanocytes of the
epidermis and some hair follicles. Compared with normal skin,
epidermal Ki-67þ and Melan-Aþ cells were increased in
lesional and perilesional skin. Cytoplasmic K15 (keratin type

1 expressed in the epidermis) immunostaining was observed
in the basal layer of the epidermis and secretory cells of some
eccrine glands, and its epidermal expression was higher in
lesional and perilesional skin than in normal skin. Cytoplasmic
staining of smooth muscle actin (SMA) was seen in arrector pili
muscle (APM), vessel walls, dermal sheath of hair follicles, and
myoepithelial cells of eccrine glands. SMAþ APM area was
higher in skin lesion than in normal skin. Intraepidermal nerve
fibers were not counted because of nonspecific staining of the
basal keratinocytes and a small number of nerve fibers in the
epidermis. PGP 9.5þ (protein gene product 9.5 expressed in
neurons and neuroendocrine cells) nerve fibers were abun-
dantly distributed in the nerve plexus and APM, and around
the eccrine ducts. The dermal nerve fiber length was higher in
lesional and perilesional skin compared with normal skin.57
Differential Diagnosis
The most characteristic manifestations of BNS are BNs,
ipsilateral hypoplasia of the breast, and ipsilateral skeletal
defects with sporadic contralateral anomalies. Although
scoliosis certainly belongs to the spectrum of this phenotype,
it seems important to realize that in a given case of co-
occurrence of BN and very mild scoliosis, it is not sufficient to
firmly establish a diagnosis of BNS.3
Becker’s nevus syndrome is a part of epidermal nevus
syndrome, which is a disease complex of epidermal nevi and
developmental abnormalities of different organ sys-
tems.100,101 Epidermal nevus syndromes include BNS, Nevus
sebaceous syndrome (Schimmelpenning–Feuerstein–Mims’s
syndrome), nevus comedonicus syndrome, Proteus syn-
drome, and congenital hemidysplasia with ichthyosiform
nevus and limb defect (CHILD syndrome).3,102
It is rather accepted as a special epidermal nevus form
such as verrucous epidermal nevus, sebaceous nevus, Jadas-
sohn’s sebaceous nevus, nevus comedonicus, eccrine nevus,
apocrine nevus, and white sponge nevus.98 Epidermal nevi
occur as a result of hamartomatous proliferation within the
embryological ectoderm layer. Therefore, they consist of
hyperplastic ectodermal structures such as keratinocytes,
hair follicles, eccrine, apocrine, and sebaceous glands. Epi-
dermal nevus syndrome usually involves the tissues origi-
nating from the ectoderm and rarely affects the mesodermal
tissues. In parallel to the structure and development of this
entity, BNS can be accepted as a variant of epidermal nevus
syndrome.41,91
A diagnosis of BNS or BN is usually made clinically, but in
doubtful cases, a tissue biopsy can be performed for histo-
pathological confirmation. The differential diagnosis of BNS
includes aplasia cutis congenital, juvenile xanthogranuloma,
epidermal nevus, syringocystadenoma papilliferum, and
solitary mastocytoma. BN includes cafè au lait macules,
congenital melanocyte nevus, plexiform neurofibroma, and
congenital smooth muscle hamartomas (CSMH).103
Also, to differentiate BN from other pigmentary disorders
such as melanocytic nevus, café au lait macules, CSMH, and
postinflammatory hyperpigmentation, histopathology may be
sometimes necessary.104 In fact, epidermal changes (elongated
Becker’s Nevus Syndrome Cucuzza et al.
and fused rete ridges, keratotic plugging, and basal pigmenta-
tion) are similar except acanthosis, but dermal alterations (mild
perivascular lymphohistiocytic infiltration, fibrosis, and smooth
muscle and sebaceous hyperplasia) are more common in BN.
Whether these histopathological differences might be related to
the diagnostic age, biopsied sites, and judgment criteria, the rete
ridge elongation and fusion, and basal hyperpigmentation seem
to be the typical features of BN.104,105
Furthermore, dermatoses and cutaneous tumors have
been described in spatial conjunction with BN, such as
acneiform lesions, dermatitis, lichen planus, pityriasis ver-
sicolor, granuloma annulare, hypohidrosis, overlying
ichthyosis, Bowen’s disease, basal cell carcinoma, lympho-
matoid papulosis, multiple leiomyoma cutis, osteoma cutis,
and underlying desmoid tumor.105–126
On the other hand, when confined to the lower body and
lacking the hallmark of unilateral breast hypoplasia, diagnosis
of BNS is more challenging. Several BNS cases located at
unusual sites may have been mistaken for other forms of
melanosis or for congenital melanocytic nevi (CMN).15 In
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fact, a decrease in bulk of subcutaneous tissue is also a well-
known feature of large and giant CMN, highlighted recently in
a study on growth and hormone profiling issues.127 Lipoma-
tous soft tissue masses in CMN with diffuse infiltration of the
nevomelanocytes within fat lobules are also on record.128 Most
of the large, giant and multiple CMNs are caused by oncogenic
mutations in codon 61 of the NRAS gene.129
Body asymmetry resulting from unilateral trunk and/or
limb hypo- or hyperplasia is the most frequent extracuta-
neous anomaly associated with cutis marmorata telangiec-
tatica congenita.130 Hypoplasia of the breast has been
observed in phacomatosis cesioflammea.131
This and other types of phakomatosis pigmentovascularis
have been shown recently to belong to the group of mosaic
heterotrimeric G-protein disorders by detection of activating
mutations in the GNA11 and GNAQ genes.132
Dysregulated adipose tissue including lipomas, lipohypo-
plasia, fatty overgrowth, and localized fat deposits is a
frequent manifestation of Proteus syndrome caused by
somatic activating mutations in the gene encoding the
growth-promoting serine/threonine kinase AKT1.133
Similarly, related overgrowth disorders with considerable
clinical overlap between each other, such as fibroadipose
overgrowth, hemihyperplasia multiple lipomatosis, congeni-
tal lipomatous overgrowth, vascular malformations, epider-
mal nevi, scoliosis/skeletal and spinal (CLOVES) syndrome, and
megalencephaly capillary malformation polymicrogyria
(MCAP) syndrome, are caused by mutations in other signaling
proteins of the RTK/PI3K/AKT/mTOR pathway and constantly
present with adipose dysregulation, either lipomatous lesions
or regional lipohypoplasia.134
Mosaicism of lethal autosomal mutations (compatible
with life only in a mosaic state) has been proven for Proteus,
CLOVES, and MCAP syndromes, as well as for large/giant
CMN.135
In contrast, the molecular basis of BNS is unknown. Based
on the spectrum of extracutaneous anomalies, one may
assume that the causative gene(s) is involved in the regulation
Journal of Pediatric Neurology
Becker’s Nevus Syndrome Cucuzza et al.
of adipose tissue distribution. A lethal autosomal mutation
only surviving as a mosaic seems to be the most likely genetic
explanation.15
Another lesion that may resemble BN is a CSMH. CSMH
characteristically appears on the trunk or extremities as a
localized skin-colored or mildly hyperpigmented and irre-
gularly shaped patch or plaque with prominent vellus hairs.
Horripilation is usually present.136 The evolution of CSMH is
generally a resolution of the infiltration, and a residual
hyperpigmented patch may be observed. The differentiation
of atypical forms of CSMH from BN is based on histology and
follow-up.5
The Becker’s nevus syndrome must not be confused with
“Becker’s syndrome,” a familial phenotype characterized by
discrete or confluent brown macules on the neck and
forearms.137,138
Management and Follow-up
There are no special issues relating to management besides
the treatment of BN. Nevertheless, the differences in andro-
gen receptors and ectoderm involvement may lead to the
alterations in the clinical course of BNS during a long period
of time. Therefore, patients should be recommended to come
for regular clinical follow-ups to examine whether any
associated abnormalities are developed in time.139 Ultra-
sound scans can be obtained to search for underlying
abnormalities ipsilateral or contralateral to the lesion.
Genetic Counseling
All but one case of BNS reported so far have been spora-
dic.31,32 The disease has been described as mosaicism invol-
ving a small extra chromosome predominantly present in
fibroblasts derived from the area of BN. Some cases were
suggestive of twin spotting as a pathogenic mechanism.94
Some authors have suggested paradominant inheritance.
Thus, an affected individual with BNS could have a small
but proven risk of passing the isolated nevus or the full-
blown syndrome to the offspring in one generation.2,3
Treatment
Although patients may feel significantly disturbed because of
the conspicuousness of a BN, therapeutic modalities are
limited. The treatment is essentially cosmetic. Potential ther-
apeutic options include electrolysis, waxing, makeup, or laser
treatment.140 Success with each modality varies widely and
depends on whether hypertrichosis, hyperpigmentation, or
both are of concern. Long-pulsed ruby and long-pulsed alex-
andrite lasers are useful for both hypertrichosis and hyper-
pigmentation.141,142 Electrolysis, waxing, and low-fluence
high-repetition-rate diode laser (808–810 mm) are useful
for hypertrichosis, whereas makeup and following lasers are
useful for hyperpigmentation: 694-mm Q-switched (QS) ruby
and 532-nm QS frequency-doubled neodymium-doped
yttrium aluminum garnet (Nd:YAG).143–145 The response to
QS lasers and IPL is often disappointing, and any partial
Journal of Pediatric Neurology
reduction in pigmentation is temporary. This might be
explained by the histopathological findings after laser treat-
ment, in which selective damage is observed in superficial
melanocytes while adnexal melanocytes persist.146 Pigment
removal by erbium-dope yttrium aluminum garnet (Er:YAG)
laser ablation was found to be superior to QS Nd:YAG laser
treatment, 1,064-nm QS Nd:YAG, 2,940-nm Er:YAG, and frac-
tional lasers.147–150 Long-pulsed 755-nm alexandrite laser, as
well as ablative and fractional ablative lasers, has been used in
the treatment of BN, but with moderate effective; in fact, the
results were impaired by postinflammatory hyperpigmenta-
tion.147,149 It is possible to treat the hypertrichosis of BN safely
and with significant efficacy using low-fluence diode lasers.
Hair removal can be performed in darker skin using longer
wavelengths, longer pulse duration, and more efficient cooling
devices.151 In contrast to traditional laser hair removal, in
which short high-fluence pulses are used, low-fluence stacked
pulse devices rely on longer, lower temperature heating of the
perifollicular tissue.
Downloaded by: Thieme Publishers Delhi. Copyrighted material.
The use of repeated low-fluence pulses over a single area
leads to cumulative dermal heating due to heat transfer from
the laser-heated hair to the perifollicular dermis. After
repeated short low-fluence pulses, the accumulated heat
in the perifollicular tissue is maintained for a longer time,
resulting in damage to the follicle and in durable hair
reduction. This approach is associated with reduced pain, a
lower risk of burns and adverse events, and is safer in darker
skin. Therefore, it is a promising tool for treating the hyper-
trichosis of BN.143
Sequelae of surgical excision may be more visible than the
original lesion. Further support for the role of androgens in
BN pathogenesis has been evident in the successful use of
spironolactone, as an antiandrogen agent, and topical fluta-
mide (4% solution) for BN-associated breast hypoplasia and
hyperpigmentation. In women with breast hypoplasia an
enlargement has been reported 1 month after the initiation
of therapy.152 Flutamide is a nonsteroidal antiandrogen that
competes with androgens for binding to androgen receptors.
Topical flutamide is absorbed into the skin, and systemic
absorption has been reported. Therefore, this treatment
should not be used in pregnant women to avoid feminization
of male fetuses, and male patients should be informed of the
potential side effects such as gynecomastia.
Spironolactone is an antiandrogen used in other derma-
tological diseases due to the hormonal action. In relation to
breast hypoplasia, its action is not fully understood but has
been proposed to respond to negative feedback of androgen
receptors. In a dosage of 50 mg/day, improvement of breast
hypoplasia has been described.152 In some cases, breast
hypoplasia and bone abnormalities, such as scoliosis, were
corrected surgically.15
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