Pediatric Dermatology Vol. 27 No.

5 492–495, 2010

Incontinentia pigmenti in a Male Infant with

Klinefelter Syndrome: A Case Report and
Review of the Literature
Evelina Buinauskaite, M.D.,* Jurate Buinauskiene, M.D., Ph.D., 
Vesta Kucinskiene, M.D., Ph.D.,* Dale Strazdiene, M.D.,à
and Skaidra Valiukeviciene, M.D., Ph.D.*
*Department of Skin and Venereal Diseases, Kaunas University of Medicine, Lithuania,  Department of
Neonatology, Kaunas University of Medicine, Lithuania, àLaboratory of Immunology and Genetics, Kaunas
University of Medicine, Lithuania

Abstract: Incontinentia pigmenti, also known as Bloch–Sulzberger

syndrome, is a hereditary, X-linked dominant disorder characterized by
abnormalities of skin, hair, teeth, eyes, and the central nervous system. It is
classically considered a male-lethal disorder leading to recurrent miscar-
riages of male fetuses. We report a rare case of a surviving baby boy with the
classic clinical features of incontinentia pigmenti that can be explained by
Klinefelter syndrome.

3 weeks. Neither of the parents had any history of der-

CASE REPORT
A 3-week-old Caucasian baby boy was admitted to
Kaunas University Hospital because of an unexplained
inflammatory skin disease and secondary pyoderma. He
was born full term (37-week gestation), and his birth-
weight was 2.7 kg. The patient was offspring of 44-year-
old women with type 1 diabetes mellitus (gravida 2, para
1, abortus 1). The previous pregnancy of the patient’s
mother was spontaneously aborted after 14 weeks’ ges-
tation. At birth, the child was noted to have blisters on
both hands, which spread to involve his legs, face, and
scalp during the first 2 weeks of life. Hyperkeratotic le-
sions as well as purulent vesicles began to develop in
previously blistered areas at approximately the age
matologic or neurologic diseases, dental anomalies, or
ocular diseases.
On physical examination at the age of 3 weeks,
assessment of growth showed the following values:
weight, 2840 g; height, 49 cm. Examination of the skin
revealed papular, vesicular, and verrucous lesions with
an erythematous base arranged in lines on the face and
scalp together with watery and purulent vesicles on upper
and lower extremities (Figs. 1 and 2). A dermatologist
was consulted, and a skin biopsy was performed because
of suspected diagnosis of incontinentia pigmenti (IP).
Histopathological examination showed acanthosis, in-
tracorneal eosinophilic pustules, light eosinophilic
spongiosis, and numerous dyskeratotic keratinocytes. In

Address correspondence to: Evelina Buinauskaite M.D.,

Kaunas University of Medicine, Clinics of Skin and Venereal
diseases, Eiveniu st. 2, LT-50009 Kaunas, Lithuania, or e-mail:
buinauskaitei@yahoo.com.

DOI: 10.1111/j.1525-1470.2010.01261.x

492  2010 Wiley Periodicals, Inc.

 Buinauskaite et al: Incontinentia pigmenti with Klinefelter Syndrome 493

Figure 1. Papular, vesicular lesions with an erythematous
base on lower extremities.
the upper dermis was spare perivascular and interstitial
infiltration with histiocytes, lymphocytes, eosinophils,
and small amounts of melanin pigment. The skin biopsy
results were consistent with the diagnosis of IP. Micro-
biological studies showed Staphylococcus aureus in the
content of blisters and vesicles. Treatment with oxacillin
for secondary pyoderma was prescribed. Cranial ultra-
sound showed subependymic cysts on the left region of
the caudate nerve with no other visible changes.
Figure 2. Papular, vesicular, and verrucous lesions with an
erythematous base arranged in lines on the face and
scalp together with watery and purulent vesicles on upper
extremities.
Blood analysis revealed leucocytosis (29.2 · 109 ⁄ L)
and eosinophilia (38 · 109 ⁄ L). Having in mind the sex of
the newborn, the typical lesions for IP and the mother’s
previous abortion, Klinefelter syndrome was suspected.
Chromosome analysis revealed a 47,XXY karyotype,
consistent with the diagnosis of Klinefelter syndrome
(Fig. 3).

Figure 3. Karyotype of the patient representing the Klinefelter syndrome.

494 Pediatric Dermatology Vol. 27 No. 5 September ⁄ October 2010

The patient was discharged from the inpatient

Eosinophilia
department after complete secondary pyoderma treat-
ment. After the diagnosis of IP and Klinefelter syndrome

Yes

Yes
Yes

NA

NA
No
was made, the patient was directed to follow-up with a
dermatologist, neurologist, and ophthalmologist be-

Conical, hypoplastic
cause of possible complications.

canine teeth
DISCUSSION

Dental
defects
Familial IP is caused by mutations in the NEMO gene

NA

NA

NA
NS

NS
and is referred to as IP2, or ‘‘classical’’ IP, whereas spo-
radic IP, the so-called IP1, which maps to Xp11, is cat-

a transient strabismus
egorized as hypomelanosis of Ito (300337) (1). The gene

proliferation in the
Normal apart from

Abnormal vascular
that is mutated in patients with IP2 is in the IKK-gamma

A pupillary block
peripheral retina
gene (IKBKG; 300248), also called NEMO, which maps

Ocular defects

bilaterally
to Xq28 (1). The NEMO ⁄ IKK-gamma gene produces a

glaucoma
protein that is essential for cells in the signaling pathways
of apoptosis and inflammatory responses. Familial IP is

NA

NA
NS

NS
an X-linked dominant disorder and is usually lethal
prenatally in males (2). Many women with IP have

defects
CNS

NA

NA

NA

NA
recurrent early miscarriages (2).

NS

NS
Although IP is usually lethal in males, about 72 cases
of male patients with IP have been reported (3–6).

A larger area

A small area
of alopecia

of alopecia
nail defects
However, real figures are difficult to quantify with pre- Hair and

Normal
cision since their publication is dispersed among spe-
NA

NA
NA
TABLE 1. Literature Review of Male Patients Diagnosed with IP and Klinefelter Syndrome

cialist journals of pediatrics, ophthalmology, genetics,

and dermatology; not all cases are published, not
present at birth

everything can be found in PubMed.

CNS, central nervous system; NA, not available in paper reviewed; NS, nothing special.
Skin findings

The International IP Consortium proposed three

mechanisms for survival of males carrying a NEMO
mutation (2): hypomorphic alleles, the 47,XXY karyo-
Yes

Yes

Yes
Yes
No

No
type (Klinefelter syndrome), and somatic mosaicism. The
new concept of hypomorphic, or ‘‘milder’’ mutation at-
and dental defects
tempts to explain the survival of male patients in families Positive for skin
Family history

carrying the common mutation (3,7). The 47,XXY

skin defects
Positive for
karyotype is one of the mechanisms by which males may
Negative
Negative

Negative
Negative

survive the effects of inheriting a lethal IP mutation, since

this karyotype establishes a heterozygous genotype that
is compatible with survival. Thus, karyotype analysis is
Karyotype

recommended in all men and boys with IP (3).

47,XXY
47,XXY

47,XXY
47,XXY

47,XXY

47,XXY

Seven cases of male IP and Klinefelter syndrome have

Cases are listed by earliest known citation.

been published in the literature (Table 1). The patient we

describe is the eighth reported case of a male infant with
15 days old

IP whose survival can be explained by the coexistence of

(at report)

8 mos old
3 mos old
2 yrs old

4 yrs old

1 yr old
1 yr old

Klinefelter syndrome.
Published diagnostic criteria for IP recommend that
Age

the diagnosis of IP should be made on the basis of at least

one major criterion, and different analysis may be needed
Garcia-Dorado (9)
Lorda-Sanchez (4)

for diagnostic studies (13,14). Incontinentia pigmenti is

Prendiville (12)
Ormerod (11)

Kenwrick (3)

characterized by typical linear skin lesions starting at

Kunze (10)

Fowell (8)

birth and spontaneously evolving in four overlapping

Citation

dermatological stages (13): early blistering with eosino-

philia (stage 1), eruption of hyperkeratotic lesions (stage
 Buinauskaite et al: Incontinentia pigmenti with Klinefelter Syndrome 495

2), hyperpigmentation along the lines of Blaschko (stage 4. Lorda-Sanchez I, de Paula M, Bardaro T et al. Varon con
3), and dermal scarring (stage 4). incontinentia pigmenti asociada a sindrome de Klinefelter.
An Esp Pediatr 2001;55:177–178.
Once the diagnosis is made, treatment should be
5. Mayer EJ, Shuttleworth GN, Greenhalgh KL et al. Novel
started, but it is important to know that there is no corneal features in two males with incontinentia pigmenti.
specific treatment for IP. The main goal is to prevent Br J Ophthalmol 2003;87:554–556.
secondary bacterial infection of skin lesions and to 6. Scheuerle AE. Male cases of incontinentia pigmenti: case
monitor closely the development of related problems. report and review. Am J Med Genet 1998;77:201–218.
7. Aradhya S, Courtois G, Rajkovic A et al. Atypical forms
The vesicles should not be touched, and the skin must be
of incontinentia pigmenti in male individuals result from
kept clean in order to avoid bacterial infections. Emol- mutations of a cytosine tract in exon 10 of NEMO (IKK-
lients and topical antibiotics may be used as needed, and gamma). Am J Hum Genet 2001;68:765–771.
local antiinflammatory treatment with glucocorticoids 8. Fowell SM, Greenwald MJ, Prendiville JS et al. Ocular
may be applied (15). Routine ophthalmologic and dental findings of incontinentia pigmenti in a male infant with
Klinefelter syndrome. J Pediatr Ophthalmol Strabismus
follow-up is essential to prevent possible sequelae. Neu-
1992;29:180–184.
rologic consultation is needed only if neurologic abnor- 9. Garcia-Dorado J, de Unamuno P, Fernandez-Lopez E
malities are present. et al. Incontinentia pigmenti: XXY male with a family
history. Clin Genet 1990;38:128–138.
10. Kunze J, Frenzel UH, Huttig E et al. Klinefelter’s
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