REVIEW

CURRENT
OPINION What’s new with common genetic skin disorders?
Jennifer L. Hand

Purpose of review
Common genetic disorders such as neurofibromatosis type I (NF1), tuberous sclerosis, basal cell nevus
syndrome (BCNS), incontinentia pigmenti, and X-linked ichthyosis have recognizable, cutaneous features.
In children, cases often present without a prior diagnosis. This review highlights new information about
diagnostic signs and care of affected patients.
Recent findings
Disruption of key regulatory pathways causes disorders such as BCNS, NF1, and tuberous sclerosis. The
discovery of associated mutations in these pathways has led to molecular targeted therapies. For example,
use of drugs such as vismodegib in BCNS and rapamycin in tuberous sclerosis complex is being studied.
Also, patient review has refined the diagnostic criteria for tuberous sclerosis and incontinentia pigmenti and
expanded the phenotype of X-linked ichthyosis. Preimplantation genetic diagnosis for disorders such as
NF1 and incontinentia pigmenti is available.
Summary
Identification of nevus anemicus or juvenile xanthogranuloma in a young child may lead to an early
diagnosis of NF1. Rapamycin offers noninvasive treatment for problematic skin lesions in pediatric patients
with tuberous sclerosis. Providers can give early advice to affected families that reproductive technologies
such as preimplantation genetic diagnosis are a consideration for future pregnancies.
Keywords
basal cell nevus syndrome, Gorlin, incontinentia pigmenti, neurofibromatosis type I, steroid sulfatase, tuberous
sclerosis, X-linked ichthyosis

INTRODUCTION helpful to identify NF1 in these young patients.

This review describes the most important recent
findings pertaining to familiar, genetic disorders
with recognizable, characteristic skin features that
herald the diagnosis. Specifically, neurofibromatosis
type I (NF1), tuberous sclerosis, basal cell nevus
syndrome (BCNS), incontinentia pigmenti, and X-
Nevus anemicus is a pale, macular birthmark caused
by permanent vasoconstriction in the superficial
dermis. Identified in 25% of patients with NF1,
nevus anemicus is potentially useful for diagnosis
in suspicious NF1. Juvenile xanthogranuloma
(Fig. 2) is also noted with a higher than expected
& &&

linked ichthyosis (XLI) are discussed. New infor-
mation relevant to the patient’s skin examination
and early diagnosis is highlighted. Also, helpful
information to prevent complications and provide
treatment is emphasized.
NEUROFIBROMATOSIS I
NF1 is one of the most common genetic disorders
with an incidence of approximately 1 in 3000. Half
of patients present with a de-novo (new) mutation
and no family history. Therefore, a pediatric care
provider is highly likely to encounter an undiag-
nosed patient. Although diagnostic criteria are
&
established (Table 1) [1 ], patients under age 2 years
&&
are less likely to meet them [2 ]. Recently, the skin
finding of nevus anemicus (Fig. 1) was reported to be
prevalence [3 ]. Ferrari et al. [2 ] proposed that each
of these two skin lesions may aid in the early diag-
nosis of NF1.
Plexiform neurofibroma is a diagnostic feature
of NF1 (Table 1). These (Fig. 3) differ from common
cutaneous neurofibromas (Fig. 4) because plexiform
neurofibroma are typically congenital, larger than
3 cm, continuously slow growing, and may degen-
erate into malignant neurofibrosarcoma in 10% of
Department of Dermatology, Medical Genetics and Pediatric and Ado-
lescent Medicine, Rochester, Minnesota, USA
Correspondence to Jennifer L. Hand, MD, Department of Dermatology,
Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. Tel: +1 507
538 8249; e-mail: hand.jennifer@mayo.edu
Curr Opin Pediatr 2015, 27:460–465
DOI:10.1097/MOP.0000000000000245

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 What’s new with common genetic skin disorders? Hand

KEY POINTS
 Nevus anemicus, in a patient under 2 years with
suspected NF1, may be useful to make the diagnosis.

 Potential use of topical rapamycin for treatment in

tuberous sclerosis has expanded to include cutaneous
hypopigmented macules and subungual tumors in
addition to facial angiofibromas.

 Presentation of a large ovarian fibroma in a pediatric

patient may indicate BCNS is present.
 Retinopathy associated with incontinentia pigmenti
appears similar to retinopathy of prematurity.
 Patients with a genetic diagnosis of XLI may have a FIGURE 1. Nevus anemicus. The pale color of the skin is
milder skin phenotype than the dark brown, polygonal caused by permanent vasoconstriction of the underlying
scales that were considered typical. blood vessels.

to be diagnosed with autism spectrum disorders

cases. In NF1, the number of cutaneous neurofibro-
mas is well known to increase at puberty, whereas
the impact of puberty on plexiform neurofibromas
had been unknown. A common concern is that
puberty will cause accelerated plexiform neurofi-
&
broma growth. A study by Dagalakis et al. [4 ] sup-
ports the idea that plexiform neurofibromas do not
increase in growth over puberty, which is reassuring
for patients.
NF1 results from a mutation in neurofibromin
that disrupts the rat sarcoma (RAS)-mitogen-acti-
vated protein kinases (MAPK) cascade. The dysregu-
lated RAS-MAPK pathway alters synaptic plasticity,
and therefore causes cognitive impairment in up to
80% of affected children. Specifically, difficulty with
social functioning has emerged as a common feature
of NF1. Children are more likely to be ‘shy’ or ‘awk-
ward’ and more likely to be bullied than unaffected
&
peers [5 ]. As a result, affected children are more likely
(ASDs), although compared with typical ASD, chil-
dren with NF1 tend to have more social concerns and
fewer restrictive and repetitive behaviors.
Disorders other than NF1, such as Noonan syn-
drome, piebaldism, and cardiofaciocutaneous syn-
drome, are also caused by mutations in the RAS-
MAPK pathway. These disorders share overlapping
clinical features with NF1 (i.e., Noonan-like facies,
café-au-lait macules) and have been renamed ‘RASo-
pathies’ as a group. Because of the change in nosol-
ogy, many prominent academic centers in the
United States have incorporated the word ‘RASop-
athy’ into the name of an appropriate clinic (e.g.,
Neurofibromatosis and RASopathy Center, Child-
ren’s Hospital of Wisconsin) and this may be a
familiar term to patients who are internet savvy.
Because of its high prevalence, NF1 is a common
referral indication to clinics that use reproductive
&
technology [6 ]. Preimplantation genetic diagnosis

Table 1. Neurofibromatosis type I diagnostic criteria

Two or more of the following are required for diagnosis:

Six or more café-au-lait macules (>0.5 cm prior to puberty or
>1 cm after puberty)
Axillary or inguinal freckling
Two or more neurofibromas of any type or one plexiform
neurofibroma
Two or more iris hamartomas (Lisch nodules)
A characteristic osseous lesion (sphenoid wing dysplasia, long-
bone dysplasia)
An optic pathway glioma
A first-degree relative with NF1 diagnosed by the above criteria

Adapted from National Institutes of Health and Hirbe and Gutmann. Lancet; FIGURE 2. Juvenile xanthogranuloma on the lateral ankle of
2014. NF1, neurofibromatosis type I. a 3-year-old girl.

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Dermatology
FIGURE 3. Plexiform neurofibroma on the waistline of a boy
with neurofibromatosis type I.
(PGD) tests embryos for a single-gene disorder prior
to placement in the uterus with a plan to implant
&
only unaffected embryos [6 ]. In 77 couples at risk of
having an NF1-affected child who underwent 156
PGD cycles, 33 cycles (21%) resulted in a live birth.
Clinicians are recommended to counsel patients
FIGURE 4. Typical cutaneous neurofibromas in a patient
with neurofibromatosis type I.
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early about the availability of this reproductive
option.
TUBEROUS SCLEROSIS COMPLEX
Tuberous sclerosis is an autosomal dominant disorder
that variably causes recognizable skin lesions, cogni-
tive impairment, and hamartomas of the kidneys,
heart, lungs, brain, and retina. In a recent update,
diagnostic criteria describing the characteristic skin
and tooth features of tuberous sclerosis were refined
&&
[7 ]. For example, a ‘forehead plaque’ was considered
a major diagnostic criterion. This was revised to
‘fibrous cephalic plaque’ because of the recognition
that typical plaques may present on the face and scalp
away from the forehead. Also, ‘gingival fibromas’
have been refined to ‘intraoral fibromas’ because
fibromas are not limited to the gingivae. Helpful
numerical requirements were added for several
cutaneous and oral lesions. For example, the number
of angiofibromas must be at least three, dental
enamel pits at least three, ungual fibromas at least
two, and intraoral fibromas at least two. For the care
of affected patients, recommendations for sun pro-
tection were added because hypomelanotic macules
are prone to sunburn and sun exposure may encour-
age development of facial angiofibromas.
Disfiguring facial angiofibromas reduce quality
&
of life [8 ]. A scoring system called the Facial Angio-
fibroma Severity Index is a new tool that allows
clinicians to quickly characterize facial disease
involvement and response to treatment. Lesions
are assessed according to size, color, and surface
area of the face involved. As the Facial Angiofibroma
Severity Index score is valid, reproducible, and
simple to perform, it is considered useful in multi-
center studies. This measurement tool is also of
interest to providers as the use of targeted medical
treatment becomes more common in the clinic.
Tuberous sclerosis complex (TSC) is caused by
mutations in TSC1 or TSC2, the genes that encode
the hamartin-tuberin complex. When disrupted,
the hamartin-tuberin complex causes over acti-
vation of mTORC1 (mammalian target of rapamy-
cin inhibitors), which leads to hamartomatous
overgrowth of affected tissues. The use of topical,
specifically targeted mTOR inhibitor medications
such as rapamycin is known to help flatten and
&
shrink facial angiofibromas in TSC [9 ]. More
recently, improvement of other TSC lesions has
been reported, including their use in hypomelanotic
& & &
macules [10 ] and subungual fibromas [11 ,12 ].
One noncutaneous cause of morbidity of tuber-
ous sclerosis is seizures. Seizures associated with
TSC, if present, typically begin between ages 3
and 5 months. With neonatal onset, however, large
Volume 27  Number 4  August 2015
 What’s new with common genetic skin disorders? Hand

malformations of the cerebral cortex and a poor syndromes in general, tumors are more likely to be
neuropsychological outcome are more likely. There- multifocal. In BCNS syndrome, ovarian fibromas are
fore, surgical treatment of epilepsy may be helpful more commonly bilateral than unilateral. Recently
and should be considered early in this group of two separate BCNS-affected girls in the pediatric age
&&
patients [13 ]. group were reported who presented with unex-
&
pected ovarian fibromas at ages 6 [17 ] and 16
&
[18 ], respectively.
BASAL CELL NEVUS SYNDROME
Basal cell nevus syndrome (BCNS), also known as INCONTINENTIA PIGMENTI
Gorlin syndrome, is an autosomal dominant dis-
Incontinentia pigmenti is an X-linked dominant
order associated with an increased risk of basal cell
disorder, usually lethal in men, with an incidence
carcinoma (BCC), especially in those younger than
&& of 0.2 in 100 000 births. Typically, incontinentia
20 years (Griner et al. [14 ]). The traditional treat-
pigmenti presents with blisters at birth and is con-
ment of BCCs in Gorlin syndrome is surgical
fused with infection, specifically herpes simplex
removal by Mohs technique. During ’Mohs,’ the
(Fig. 5). For experienced clinicians, incontinentia
surgeon checks each tissue margin for evidence of
pigmenti is recognizable by its characteristic appear-
tumor and removes only the affected portion in
ance and pattern along developmental skin lines
another stepwise procedure until all margins are &
[19 ]. Diagnostic criteria were first established in
clear of tumor. Many studies support that Mohs &&
1993. More recently, Minic et al. [20 ] updated
surgery has a higher cure rate for BCC with possible
and refined the criteria pertaining to skin. Diagnostic
disadvantages for patients being travel distance to a
descriptions were expanded to include details about
qualified center, an increased final defect size, and
skin lesions in four possible stages: vesicular, verru-
increased cost. An impressive case study appeared
cous, hyperpigmented, and hypopigmented/atro-
documenting a woman with BCNS who underwent
phic appearing lesions that follow developmental
more than 730 BCCs removals by a plastic surgeon
skin lines. The timing and appearance of each stage
by simple excision rather than Mohs over 40 years.
may overlap, but typically all cases present within 1
Many excisions had positive margins that were not &
&& week of birth [21 ]
removed with a second procedure [14 ]. She was
pictured with an excellent cosmetic outcome.
Targeted medical therapies are under develop-
ment. The Ptch1 (Patched 1) gene encodes a tumor
suppressor protein, which is disrupted in BCNS. Nor-
mally, Patched 1 works together with transmembrane
protein SMO (smoothened) to repress the develop-
ment of BCCs. Vismodegib is a drug that specifically
inhibits SMO. In a randomized, double-blind,
placebo-controlled clinical trial of 41 BCNS patients,
patients given the drug had statistically significant
&&
reduction in number and size of BCCs [15 ]. Fifty-four
percent of patients discontinued treatment because of
side-effects such as dysgeusia (loss of taste), muscle
cramps, hair loss, and weight loss. Also, tumors
recurred as resistance to the drug developed.
Additional strategies for medical treatment such
as a combinational approach with other drugs are
&&
being considered [15 ]. One such strategy is the
application of a topical retinoid medication, tazar-
&
otene, as chemoprevention [16 ]. In a randomized,
double-blind, vehicle controlled study of 34 BCNS
patients, however, no benefit of chemoprevention
was demonstrated with the use of tazarotene after
&
3 years of follow-up [16 ].
Ovarian fibromas are uncommon in the
pediatric age group; however, they are common in
Gorlin syndrome, occurring in 14–24% of affected FIGURE 5. Typical blister-like lesions that follow developmental
women. As is typical of genetic tumor predisposition skin lines of Blaschko in an infant with incontinentia pigmenti.

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Dermatology

In all cases of incontinentia pigmenti, an IKBKG preimplantation genetic screening. Affected male
gene mutation disrupts a protein important for cell pregnancies usually end in miscarriage. Kim et al.
&
survival that leads to an increased risk of cell apop- [25 ] reported a successful pregnancy to 29-year-old
tosis. Most patients (78%) have a similar deletion of woman with phenotypically mild incontinentia pig-
&
exons 4 through 10 [19 ]. Repetitive DNA sequences menti who had suffered three male miscarriages.
surrounding these particular exons create an unusu- Genetic testing for DNA on her blood revealed
ally high frequency of disease-associated recombi- a pathogenic deletion in exon 9 of the IKBKG
nation errors. Because of improved understanding gene, which was useful to test embryos prior to
of this structural architecture of the gene, the IKBKG implantation.
locus is now considered a ‘genomic instability
&
region’ linked to an inherited disease [19 ]. X-LINKED ICHTHYOSIS
Because incontinentia pigmenti potentially affects
XLI is an X-linked recessive disorder that affects one
ectodermal structures: hair, teeth, skin, and sweat
out of every 1500 males. Clinically, XLI is character-
glands, it is considered a member of the broader group
ized by dark brown, polygonal scaling of the skin,
of ectodermal dysplasias. In a large Swedish study,
especially on extensor surfaces. Up to 90% of cases
tooth findings were examined specifically. These
are caused by a chromosomal microdeletion that
authors noted not only oligodontia, but also that
removes the entire STS gene. As use of screening that
patients had abnormally shaped teeth, especially con-
interrogates the entire genome (i.e., chromosomal
ical and tapered maxillary incisors and notching on
microarray testing) increases, individuals are being
the incisors and talon cusps. Almost half of the affected
diagnosed in the laboratory that may have not been
patients had lower salivary secretion than expected.
recognized previously. A group of patients identified
The most frequently reported tooth changes were
incidentally in the laboratory as having an STS
dental shape abnormalities, hypodontia, and delayed
deletion was found to have a milder skin phenotype
dentition, all of which were added to the updated
of dryness or eczema, or both. This group lacked dark,
diagnostic criteria. These authors recommended that
polygonal scale, suggesting that a milder phenotype
assessment of salivary secretion should be part of every
& may be more common than previously realized,
new incontinentia pigmenti patient assessment [22 ].
especially when the diagnosis is made incidentally
Eye involvement is increasingly recognized in &
[26 ]. This expanded phenotype may be important
incontinentia pigmenti. A review by Chen et al.
&& for others considering the implications of an inci-
[23 ] reports vision-threatening eye disease in 20%
dental XLI diagnosis, as the literature describes at
of affected individuals. An unexpectedly high number
least five pregnancy terminations because of parental
of patients have persistence of fetal vasculature on the
concern about the predicted skin phenotype based
retina, similar to retinopathy of prematurity. All
on prenatal laboratory testing.
infants, especially if abnormality is suspected, should
Females inherit the equivalent of one X chromo-
have an eye examination, preferably under anesthesia
some from their mother and one from their father.
and with fluorescein angiography in the first few weeks
Within each cell, one X is inactivated. In XLI, the
of life. The frequency of follow-up should be deter-
mutated STS region is unusual because it escapes
mined by the degree of retinopathy, with an increased
&& inactivation, so in any female cell, both copies of
interval if disease is stable by age 2 years [23 ].
the STS gene are expressed. Therefore, a carrier female
Tumors under the nail are known to be a com-
shows no features of the disorder. In 2014, a rare case
plication of incontinentia pigmenti, typically appear-
of an affected female was reported because of a
ing after puberty. Incontinentia pigmenti-related
homozygous STS deletion, one on each X chromo-
subungual tumors are thought to be a benign process; &
& some [27 ].
however, Pena and Brewer [24 ] reported a case of a
young woman with incontinentia pigmenti treated
with amputation for a presumed squamous cell car- CONCLUSION
cinoma presenting on the subungual thumb. She later In summary, recent advances for common genoder-
presented with similar appearing verrucous papules matoses include refined diagnostic criteria based on
on other fingers that were diagnosed pathologically patient review by experienced teams of clinicians
as ‘subungual tumor if incontinentia pigmenti.’ These (tuberous sclerosis, incontinentia pigmenti). A
authors cautioned that possibly the squamous cell similar review of patient information has expanded
carcinoma was misdiagnosed and clinicians should the expected phenotype of a laboratory diagnosed
be aware of subungual tumors as a benign, late com- disorder (XLI) to include milder forms. Advances
plication of incontinentia pigmenti. also include the use of targeted medical therapies to
Progress has been made in prenatal diagnosis, replace traditional surgery (tuberous sclerosis,
evidenced by a report of successful pregnancy by BCNS). Finally, new genetic technology such as

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preimplantation genetic diagnosis (NF1, inconti-
nentia pigmenti) is directly impacting patient care.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
1. Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary ap-
& proach to care. Lancet Neurol 2014; 13:834–843.
This review describes tumors and growths affecting various disparate organ
systems, necessitating a multidisciplinary approach for patients with NF1.
2. Ferrari F, Masurel A, Olivier-Faivre L, Vabres P. Juvenile xanthogranuloma and
&& nevus anemicus in the diagnosis of neurofibromatosis type 1. JAMA Dermatol
2014; 150:42–46.
This study proposes that the nevus anemicus may aid in the early diagnosis of NF1
in children younger than 2 years of age.
3. Jans SR, Schomerus E, Bygum A. Neurofibromatosis type 1 diagnosed in a
& child based on multiple juvenile xanthogranulomas and juvenile myelomono-
cytic leukemia. Pediatr Dermatol 2015; 32:e29–e32.
This well-written article reviews the association of NF1 and juvenile xanthogranu-
loma.
4. Dagalakis U, Lodish M, Dombi E, et al. Puberty and plexiform neurofibroma tumor
& growth in patients with neurofibromatosis type I. J Pediatr 2014; 164:620–624.
This study provides a detailed study of 41 patients by the National Institutes of
Health, which shows no evidence that plexiform neurofibroma growth accelerates
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This is a study of 102 patients with NF1 assessed for evidence of ASDs. The
discussion of the results clarifies the importance of social cognition deficits that are
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behaviors are more common in ASDs than in NF1.
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This study describes the status of technology being used for preimplantation
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7. Teng JM, Cowen EW, Wataya-Kaneda M, et al. Dermatologic and dental
&& aspects of the 2012 International Tuberous Sclerosis Complex Consensus
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This is a consensus statement compiled by multiple experts following a review of
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This article provides a description of the validation of an assessment tool (Facial
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& sclerosis complex: the effect of topical rapamycin and concomitant laser
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This article presents a series of cases, with photographs, of individuals treated by a
combination of topical rapamycin and laser therapy.
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& the efficacy of topical rapamycin therapy against hypomelanotic macules in
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This is a case series of individuals treated with topical rapamycin for hypomelanotic
macules in tuberous sclerosis.
1040-8703 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
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11. Muzic JG, Kindle SA, Tollefson MM. Successful treatment of subungual
& fibromas of tuberous sclerosis with topical rapamycin. JAMA Dermatol
2014; 150:1024–1025.
This is a case study of a patient treated with topical rapamycin for subungual
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This is a case study of a patient treated with topical rapamycin for subungual
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&& with tuberous sclerosis complex. Eur J Paediatr Neurol 2014; 18:714–721.
This is a well-written article that details evidence for a poor prognosis in children
with tuberous sclerosis who have an unusually early onset of seizures in the
neonatal period.
14. Griner D, Sutphin D, Sargent LA. Surgical management of Gorlin syndrome: a
&& 4-decade experience using local excision technique. Ann Plast Surg 2015;
74:467–470; doi: 10.1097/SAP.0000000000000052. [Epub ahead of print]
This article discusses an alternative approach for patients with BCNS considering
surgical removal of skin cancer. Although only a single case study, the patient is
followed for 40 years, adding to its value. Patients often ask about this option.
15. Athar M, Li C, Kim AL, et al. Sonic hedgehog signaling in basal cell nevus
&& syndrome. Cancer Res 2014; 74:4967–4975.
This review provides a thorough discussion of the molecular mechanisms causing
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16. Tang JY, Chiou AS, Mackay-Wiggan JM, et al. Tazarotene: randomized,
& double-blind, vehicle-controlled, and open-label concurrent trials for basal
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syndrome. Cancer Prev Res (Phila) 2014; 7:292–299.
This is a well-designed study, which ultimately demonstrates a lack of benefit for
the chemoprevention of BCC in patients with BCNS.
17. Jimbo T, Masumoto K, Urita Y, et al. Nevoid basal cell carcinoma syndrome
& with a unilateral giant ovarian fibroma in a Japanese 6-year-old girl. Eur J
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This is a case study of a huge ovarian fibroma in a child with BCNS.
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& 164:1501–11501; e1501.
This is a brief study with excellent radiologic images of jaw keratocyst and ovarian
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& report of new mutations and complex genomic rearrangements leading to
incontinentia pigmenti disease. Hum Mutat 2014; 35:165–177.
This is a review of the current knowledge about mutations that cause incontinentia
pigmenti and the molecular mechanisms that predispose to them.
20. Minic S, Trpinac D, Obradovic M. Incontinentia pigmenti diagnostic criteria
&& update. Clin Genet 2014; 85:536–542.
This article provides rationale and details behind updated diagnostic criteria for
incontinentia pigmenti in a summary article.
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& literature review. Exp Ther Med 2014; 8:1797–1806.
This is a case series of six patients diagnosed with neonatal incontinentia pigmenti
in China.
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This article provides a detailed review of the expected oral findings in several
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23. Chen CJ, Han IC, Tian J, et al. Extended follow-up of treated and untreated
&& retinopathy in incontinentia pigmenti: analysis of peripheral vascular changes
and incidence of retinal detachment. JAMA Ophthalmol 2015; 133:542–
548; doi: 10.1001/jamaophthalmol.2015.22. [Epub ahead of print]
This article provides important information about vision loss as a potentially
devastating complication of incontinentia pigmenti. Clinical signs that may predict
complications in the eye and recommendations for ophthalmologic examination
and follow-up are discussed in this article.
24. Pena ZG, Brewer JD. Multiple subungual squamous cell carcinomas in a
& patient with incontinentia pigmenti. Dermatol Surg 2014; 40:1159–1161.
This is a case study that outlines possible misdiagnosis of benign subungual
tumors.
25. Kim MJ, Lyu SW, Seok HH, et al. A healthy delivery of twins by assisted
& reproduction followed by preimplantation genetic screening in a woman with X-
linked dominant incontinentia pigmenti. Clin Exp Reprod Med 2014; 41:168–173.
This a case study describing the successful use of PGD in incontinentia pigmenti.
26. Hand JL, Runke CK, Hodge JC. The phenotype spectrum of X-linked
& ichthyosis identified by chromosomal microarray. J Am Acad Dermatol
2015; 26:617–627; doi: 10.1016/j.jaad.2014.12.020. [Epub ahead of print]
This study describes a group of patients who were studied after having been
diagnosed with steroid sulfatase deficiency (XLI) by molecular testing. The
phenotype they expressed was, in general, less severe than expected based on
previous descriptions in the literature.
27. Murtaza G, Siddiq S, Khan S, et al. Molecular study of X-linked ichthyosis:
& report of a novel 2-bp insertion mutation in the STS and a very rare case of
homozygous female patient. J Dermatol Sci 2014; 74:165–167.
This is a rare case study of a woman with molecularly confirmed XLI.
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