CASE REPORT

Niger J Paed 2015; 42 (3):231 –233

Mukhtar-yola M

Audu LI

Otuneye AT

Mairami AB

Otubelu EC

Kefas JG

Hypomelanosis of Ito: Case report

of a rare neurocutaneous syndrome

in a neonate and review of the

literature.

Hamza N

DOI:http://dx.doi.org/10.4314/njp.v42i3.12

Accepted: 26th March 2015

Abstract: Hypomelanosis of Ito

HI) though said to be the third-

most common neurocutaneus

disorder, is rarely reported in pae-

diatric practice in Africa. A high

index of suspicion must be main-

tained in children with cutaneous

lesions as a seizure may be the

first symptom that may bring the

child to attention. A case of HI in a

neonate is hereby reported to sen-

sitize clinicians about this rela-

tively uncommon disorder

(

)

Mukhtar-yola M

Audu LI, Otuneye AT

Mairami AB, Otubelu EC

Kefas JG, Hamza N

Department of Paediatrics,

National Hospital Abuja.

Nigeria.

Email: mariyamukhtar@yahoo.com

Introduction

Case description

was no history of abnormal vaginal discharge, body

rash, or fever. Mother is not a known hypertensive or

diabetic and did not have gestational diabetes mellitus.

Obstetric ultrasound scan done at 32 weeks gestation

showed features of hydrocephalus.

Hypomelanosis of Ito is characterized by presence of

unilateral or bilateral whorls, streaks and patches of hy-

popigmented skin lesions and often associated with neu-

rological and musculoskeletal manifestations. Ito first

described it in 1951.1 Its pathogenesis is strongly linked

to genetics, as up to 52% may have some chromosomal

Labour started spontaneous at 40/52 and was prolonged,

necessitating an emergency caesarean delivery. Apgar

scores were not documented in the referral notes. Father

is a 44-year-old civil servant with secondary level of

education; mother is a 35 year old housewife with terti-

ary level of education. Patient is the 6th of parents 6

children. The 3rd child, male, now aged 7years had a

febrile seizures at 3years of age for which he was placed

on carbamazepine for 2yrs with complete control of sei-

zures and has been off anticonvulsant for 2 years now.

He did not have any skin changes and there was no his-

tory of a similar disorder in other family members. The

marriage is non consanguinous and they all reside in a

two-bedroom apartment in the outskirts of Abuja.

abnormalities and familial cases have been reported . It

is a neurocutaneus disorder that occurs in 1 in 10,000

clinic visits . This report is meant to sensitize clinicians

about this relatively uncommon syndrome since there is

paucity of data in Nigeria.

Case presentation

Baby M. presented at the age of 20 hours with a history

of seizures from the first hour of life and fever for 14

hours prior to presentation which was high grade and

intermittent. Convulsions were initially focal involving

the left side of the body with secondary generalization

for 3-5 minutes. The infant remained conscious and alert

during most episodes of convulsions. Baby had been on

glucose water prior to transfer. She did not have any

other constitutional symptoms.

She was delivered in a private hospital in Abuja to a

Fulani mother who had a supervised pregnancy from 24

weeks of gestation. The Pregnancy was uneventful,

mother’s serological tests for HIV, HBsAg, VDRL and

HCV were all negative though she was positive for cy-

tomegalovirus and Herpes simplex IgG. She had no his-

tory of exposure to irradiation; no consumption of un-

prescribed medications both orthodox and herbal. There

The baby was found to be floppy, in respiratory distress,

and had a meconium stained cord and nasal secretions.

The birth weight was 4.5kg, she was macrocephalic

(OFC 41cm i.e 97TH centile), and left sided frontal

bossing with wide anterior fontanelle measuring 8x 6cm.

she also had right-sided hemihypertrophy and extra dig-

its on her hands. The skin showed bilateral hypopigmen-

tation with irregular borders occurring in whorls over

the trunk and buttocks and as streaks over the limbs fol-

lowing the lines of Blaschko mostly on the right side of

the body. (Fig. 1) The face, palm and soles of feet were

spared. She convulsed more than 20 times a day. Sys-

temic examination was essentially normal and there

were no eye changes as reported by the opthalmologist

A diagnosis of Hypomelanosis of Ito with meconium

aspiration syndrome was made. Her blood sugar re-

mained normal throughout admission. The serum cal-

cium was initially 1.76mmol/L and was corrected within

Discussion

Hypomelanosis of Ito (HI) is a sporadic neurocutaneous

disorder characterized cutaneously by hypopigmented

skin lesions arranged in whorls or streaks along the lines

8hours. All other electrolytes were normal. Full blood

of Blaschko . The lines of Blaschko are relatively con-

count showed leukocytosis of 19.9 x109/L, with neutro-

phils of 67%. The blood culture yielded no growth. An

MRI of the brain revealed absence of sulci and gyri and

absence of the frontal lobe of the right ventricle in place

of which was a harmatoma that extended into the ventri-

cle causing mild dilatation of the lateral ventricles. (See

fig. 2) Chest x-ray and abdomino-pelvic ultrasound scan

were essentially normal. For further evaluation, we

planned a skin biopsy, EEG, Echocardiography and

chromosomal studies but the parents did not consent

Patient was managed by a multidisciplinary team

sistent and distinct from dermatomal lines. They repre-

sent lines of orderly migration of mesodermal and ecto-

dermal precursors during embryogenesis . Though mul-

tisystem involvement is common, it is heterogenous in

presentation and commonly manifests with involvement

of the neurologic and musculoskeletal systems. Our pa-

tient had cutaneous, neurologic and musculoskeletal

manifestations.

Minor Ito first described the syndrome in a 22yr old

Japanese young lady in 1951 . She presented with depig-

(

paediatricians, dermatologist, ophthalmologist and car-

mented lesions on half of her body with no other ex-

tracutaneous manifestation except for asymmetry of the

breast. Ito coined the name nevus depigmentosus sys-

tematicus bilateralis to refer to this condition. The oc-

currence of extra cutaneous manifestations of HI have

been reported with varying frequencies; 30% by Nehal

diologist) and treated with supplemental Oxygen, intra-

venous fluids and intravenous antibiotics. For seizure

control she was placed on titrated doses of phenobarbi-

tone and eventually carbamazepine. Seizure control

however remained poor, she is currently having regular

neurologic and neurosurgical consults.

et al and nearly 100% by Ruiz- Maldonado et al . In

967, Hamada et al confirmed the association between

the skin lesions and systemic abnormalities, including

mental retardation . Pascal-Castroviejo et al delineated

Fig 1: Skin showing

hypopigmented

streaks and whorls

the full spectrum of associated neurological abnormali-

ties in a systematic study of the largest series published .

Some diagnostic criteria for hypomelanosis of Ito syn-

drome were established in 1992 . These criteria link the

diagnosis to the presence of systemic non-

dermatological (eg, CNS, skeletal) or chromosomal ab-

normalities. These criteria however excluded patients

with only dermatological manifestations. Some re-

searchers believe that hypomelanosis of Ito does not

represent a distinct disorder but rather a symptom com-

mon to a group of disorders involving genetic

mosaicism.

Epidemiological data on this syndrome is limited, It has

an incidence of 1:10000 to 1:8000. In a pediatric neurol-

ogy service in Spain, 1 in 600-700 patients referred was

diagnosed with hypomelanosis of Ito syndrome. It is

diagnosed in 1 of every 7,805 general pediatric outpa-

tient visits, 1 of every 790 pediatric dermatology clinic

visits, and 1 of every 2,983 children in a general pediat-

Fig 2: MRI Brain: showing

absence of sulci and gyri,

hamartoma in the frontal lobe

ric service . Approximately three quarters of the patients

with typical skin lesions have systemic manifestations

especially affecting the central nervous system . Unlike

incontinentia pigmentia that has a clear sex preponder-

ance, HI is only slightly more common in females than

males but the severity of systemic manifestations ap-

pears to be similar in both sexes. The incidence in Nige-

ria has not been reported from the best of our knowl-

edge. Data in relation to age of diagnosis are usually

reported in regard to the skin manifestations of HI syn-

drome. Typical skin lesions are initially demonstrated

during the first year of life in as many as 70% of

patients; they are noticeable at birth in 54% of patients

and rarely, lesions are not visible until mid childhood .

,4,5

Patients with skin manifestations suggestive of hypome-

lanosis of Ito with and without systemic alterations have

been described in the same family, demonstrating that

hypomelanosis of Ito syndrome’s systemic involvement

can vary. Although hypomelanosis of Ito syndrome is

most commonly a de novo occurrence, familial cases

appear to be transmitted as an autosomal dominant trait.

Approximately 10% of the patients report a family his-

tory of seizures or epilepsy, but the phenotypic expres-

sion varies; therefore, pigmentary changes may be the

to 100% . One half to two thirds of patients have

mental retardation _,w₄_,₅ith autism spectrum disorders

occurring in 11% . Up to 50% have seizures, which

are mainly generalized tonic clonic . A significant por-

tion of those with partial seizures have cerebral dyspla-

sias occurring contralateral to the side of the hypome-

lanotic skin lesions, our patient had a harmatoma and

ventriculomegally on the contralateral side with resul-

tant obvious macrocephally. Of those with seizures, 40-

70% may be controlled while the remainders have in-

tractable seizures like this reported case. Hemimegalen-

cephaly is an occasional finding. Hypotonia with motor

developmental delays are common. Brain tumours, both

benign and malignant are also associations.

only clue to the genetic basis . A sibling of our patient

had seizures but did not have the classic skin changes

associated with HI.

The pathogenesis of hypomelanosis of Ito syndrome is

strongly linked to its genetics. A karyotype analysis sur-

vey performed on 115 patients revealed chromosomal

Ocular manifestations are present in one fifth of patients.

They include unilateral heterochromic iris with hypopig-

mentation of the cornea, strabismus, megalocornea,

symblepharon, optic atrophy, macrophthalmia, mi-

crophthalmia, scleral melanosis and nystagmus. Our

patient however did not have any ocular manifestation.

Cardiac anomalies may also be present in a few cases

such as ventricular or atrial septal defects, tetralogy of

fallot, pulmonary stenosis, right bundle branch block or

cardiomegaly have all been reported. Genitourinary ab-

normalities include hypospadias, micropenis, cryp-

torchidism, single or ectopic kidneys, urethral duplica-

tio₈n_,₉,_,₁₀gynaecomastia, nephritis and precocious puber-

anomalies in 60 (52%) . Many patients have a chromo-

somal mosaic pattern, often leading to the generation of

two cell lineages, which produce patterns of hypopig-

mented and hyperpigmented skin. Alterations in X-

chromosomes such as inactivation, activation, and mo-

saicism are the main causes of different patterns of cell

behavior in the skin . Perhaps this can also be found in

other tissues, such as the fund us (tessellated or radial

pigmentation of the fundi), iris (hypopigmentation), and

the brain (areas with abnormal cell morphology and

neuroblast migration side by side with normal patterns) .

Our patient did not have any eye changes, but had a dys-

plasia in the brain resulting in a hamartoma.

. Other abnormalities affecting the hair, fingernails

and dentition have also been reported. Hepatomegaly,

segmental dilatation of the colon and hernias (inguinal,

diaphragmatic and umbilical) are seen in some patients

Musculoskeletal signs are common in HI; our patient

had right-sided hemihypertrophy, and polydactaly. Mus-

culoskeletal signs are observed in more severe pheno-

types and include short stature, pectus carinatum, scolio-

sis and asymmetry with hemihypertrophy usually along

the hypopigmented areas. Bilateral hypertrophy is seen

8,9,10

Hypomelanosis of Ito is the third most common neuro-

cutaneous disorder however there is a paucity of data on

reported cases in Nigeria. It is a challenging diagnosis

for both the physician and the parents especially in those

patients with neurologic involvement and poor seizure

control. Our patient had intractable seizures that could

not be controlled despite several medications. The high

frequency of seizures resulted in fever, poor weight gain

and parental anxiety. Early diagnosis is important so that

appropriate measures can be taken and parental counsel-

ing will be done.

8,9,10

in some cases with generalized hypomelanotic skin

These patients show coarse facies and macrocephaly.

Abnormalities of the digits may also present as syndac-

8,9,10

tyly, clinodactyly, polydactyly or bifid thumbs

Neurological abnormalities represent the most severe

complications of HI and there is great discrepancy

between reported prevalence figures ranging from 30%

References

Nehal KS, PeBenito R, Orlow SJ.

Ito M. A singular case of naevus

depigmentosus systematicus bilat-

eralis. Jpn J Dermatol. 1951;61:31

8. Esquivel EE, Pitt MC, Boyd SG.

Hypomelanosis of ito- a case re-

port. Neuropediatrics 1991;22:216

-219

9. Glover M.T, Brett E.M, Atherton

DJ. Hypomelanosis of Ito: spec-

trum of disease. J Pediatr 115: 75-

10. Ruggieri M, Pavone L. Hypome-

lanosis of Ito: clinical syndrome or

just phenotype. J Child Neurol

2000, 15: 635-644

Analysis of 54 cases of hypopig-

mentation and hyperpigmentation

along the lines of Blaschko. Arch

Dermatol. 1996;132(10):1167-70.

Hamada T, Saito T, Sugai T, Mo-

rita Y. "Incontinentia pigmenti

achromians (Ito)". Arch Dermatol.

Ruiz-Maldonado R, Toussaint S,

Tamayo L, Laterza A, del Castillo

V. Hypomelanosis of Ito: diagnos-

tic criteria and report of 41

967;96(6):673-6

cases. Pediatr Dermatol. 1992;9

CamilaK Janninger, Dirk M Eston.

Pediatric hypomelanosis of ito.

Medscape 2013.

Sybert VP. Hypomelanosis of Ito:

a description, not a diagnosis. J

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(1):1-10

Pascual-Castroviejo I, Lopez-

Rodriguez L, de la Cruz Medina

M, Salamanca-Maesso C, Roche

Herrero C. Hypomelanosis of Ito.

Neurological complications in 34

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(2):124-9.