Hypomelanosis of Ito" Neumlogi¢ Samuel E. Golden, biD and Allen M. Kaplan, MD Hypomelanosis of Ito is an uncommon, but clinically recognizable neutocutaneous syndrome. Neurologic complications are frequent and most commonly include seizures, psychomotor delays, changes in tone, and gait disturbances. Four patients with hypomelanosis of Ito and neurologic complications are presented; one patient had an assodated chromosome aberration not reported previously. Golden SE, Kaplan AM. Hypomelanosis of Ito: Neurologic complications. Pediatr Neurol 1986; 2:170-4. Introduction Hypomelanosis of Ito (incontinentia pigmenti achromians), an uncommon neurocutaneous syndrome, consists of characteristic hypopigmented cutaneous lesions associated with frequent central nervous system (CNS) abnormalities. Approximately 40% of cases have CNS manifestations, particularly seizures and psycho- motor delays [1]. We report clinical and radiographic data for four patients with hypomelanosis of Ito (HI) (Table 1), and review the literature with particular emphasis on associated neurologic abnormalities. Case Reports Case 1. An 11-month-old male infant was referred for neurologic evaluation because of developmental delay and peculiar skin depigmentation. There had been a prolonged labor and a nuchal cord. Apgar scores were 7 at 1 minute and 8 at 5 minutes. There were no major neonatal complications. The father and a distant cousin had similar swirling hypopigmented skin lesions. General physical examination revealed polydactyly of both hands and the right foot, hypertelorism, small palpebral fissures with anti- mongolian slant, and a small, beaked nose. Hypopigmented skin lesions were present in a marbled pattern. Neurologic examination revealed moderate delays in all developmental milestones l hypotonia, and left-sided spasticity. Cranial nerve examination was normal. The deep tendon responses were bilaterally and symmetrically increased. Serum chemistries, electrolytes, and blood counts were normal. Chest x-ray, electrocardiogram, and electromyography studies also were normal. Chromosome analysis demonstrated a mosaic trisomy 18 pattern. Cranial computed tomography (CT) at I year of age documented cortical atrophy with asymmetrical ventricular dilatation and a large cistema magna associated with hypoplasia of the cerebellum (Fig 1). Formal neurodevelopmental evaluation at 41/2 years of age at the Central Arizona Child Evaluation Center revealed language skills at a 15-month-old level and an overall cognitive function consistent with 24 months of age. Case 2. A 1-month-old infant was referred for neurotogic evaluation because of the presence of skin lesions since birth suggestive of a neurocutaneous disorder. The infant was the: product of an uncomplicated pregnancy, labor, and delivery, and had a normal neonatal course. The mother had a nevus of Ota involving the periorbital region. General physical examination revealed several discrete areas of hypopigmented macules in whorl configurations on the left leg, chest, back, and buttocks (Fig 2). There were no vesicular or verrucous lesions. Neurologic examination was normal except for mild generalized hypertonicity with hyperreflexia and unsustained ankle clonus. Basic laboratory evaluations and a cranial CT were normal. No psychometric studies were performed. Case 3. A 1-year-old infant was evaluated because of develop- Table 1. N ~ ~ dhypomdaMm dIto: Pmsens series Case Age Sex Neumlogic Findings CT 1 11 mos M Hypotonia, Asymmetry of hemiparesis, ventricular system, mosaic trisomy 18 cerebellar hypoplasia 2 i mo M Hypertonicity Normal 3 1 yr F Hypotonicity Mild cerebral dysplasia 4 3 mos M Speech delay Normal Psychometric Status Moderate psychomotor delay Not tested Mild developmental delay Mild developmental delay From the Departments of Pediatric Neurology and Pediatrics; Phoenix Children's Hospital and Maricopa Medical Center; Phoenix, Arizona. Communications should be addressed to: Dr. Kaplan; Deparxment of Pediatric Neurology; Phoenix Children's Hospital; 909 East Brill Street; Phoenix, AZ 85006. Received January 17, 1986; accepted April 8, 1986. 170 PEDIATRIC NEUROLOGY Vol. 2 No. 3
Transcript
Hypomelanosis of Ito" Neumlogi¢
Samuel E. Golden, b iD and Allen M. Kaplan, MD
Hypomelanosis of Ito is an uncommon, but clinically recognizable neutocutaneous syndrome. Neurologic complications are frequent and most commonly include seizures, psychomotor delays, changes in tone, and gait disturbances. Four patients with hypomelanosis of Ito and neurologic complications are presented; one patient had an assodated chromosome aberration not reported previously.
Golden SE, Kaplan AM. Hypomelanosis of Ito: Neurologic complications. Pediatr Neurol 1986; 2:170-4.
Introduction Hypomelanosis of Ito (incontinentia pigmenti
achromians), an uncommon neurocutaneous syndrome, consists of characteristic hypopigmented cutaneous lesions associated with frequent central nervous system (CNS) abnormalities. Approximately 40% of cases have CNS manifestations, particularly seizures and psycho- motor delays [1].
We report clinical and radiographic data for four patients with hypomelanosis of Ito (HI) (Table 1), and
review the literature with particular emphasis on associated neurologic abnormalities.
Case Reports Case 1. An 11-month-old male infant was referred for neurologic
evaluation because of developmental delay and peculiar skin depigmentation. There had been a prolonged labor and a nuchal cord. Apgar scores were 7 at 1 minute and 8 at 5 minutes. There were no major neonatal complications. The father and a distant cousin had similar swirling hypopigmented skin lesions.
General physical examination revealed polydactyly of both hands and the right foot, hypertelorism, small palpebral fissures with anti- mongolian slant, and a small, beaked nose. Hypopigmented skin lesions were present in a marbled pattern. Neurologic examination revealed moderate delays in all developmental milestones l hypotonia, and left-sided spasticity. Cranial nerve examination was normal. The deep tendon responses were bilaterally and symmetrically increased.
Serum chemistries, electrolytes, and blood counts were normal. Chest x-ray, electrocardiogram, and electromyography studies also were normal. Chromosome analysis demonstrated a mosaic trisomy 18 pattern. Cranial computed tomography (CT) at I year of age documented cortical atrophy with asymmetrical ventricular dilatation and a large cistema magna associated with hypoplasia of the cerebellum (Fig 1). Formal neurodevelopmental evaluation at 41/2 years of age at the Central Arizona Child Evaluation Center revealed language skills at a 15-month-old level and an overall cognitive function consistent with 24 months of age.
Case 2. A 1-month-old infant was referred for neurotogic evaluation because of the presence of skin lesions since birth suggestive of a neurocutaneous disorder. The infant was the: product of an uncomplicated pregnancy, labor, and delivery, and had a normal neonatal course. The mother had a nevus of Ota involving the periorbital region.
General physical examination revealed several discrete areas of hypopigmented macules in whorl configurations on the left leg, chest, back, and buttocks (Fig 2). There were no vesicular or verrucous lesions. Neurologic examination was normal except for mild generalized hypertonicity with hyperreflexia and unsustained ankle clonus.
Basic laboratory evaluations and a cranial CT were normal. No psychometric studies were performed.
Case 3. A 1-year-old infant was evaluated because of develop-
Table 1. N ~ ~ d h y p o m d a M m dIto: Pmsens series
Case Age Sex Neumlogic Findings CT
1 11 mos M Hypotonia, Asymmetry of
hemiparesis, ventricular system,
mosaic trisomy 18 cerebellar hypoplasia
2 i mo M Hypertonicity Normal
3 1 yr F Hypotonicity Mild cerebral
dysplasia
4 3 mos M Speech delay Normal
Psychometric Status
Moderate
psychomotor
delay
Not tested
Mild developmental
delay
Mild developmental
delay
From the Departments of Pediatric Neurology and Pediatrics; Phoenix Children's Hospital and Maricopa Medical Center; Phoenix, Arizona.
Communications should be addressed to: Dr. Kaplan; Deparxment of Pediatric Neurology; Phoenix Children's Hospital; 909 East Brill Street; Phoenix, AZ 85006. Received January 17, 1986; accepted April 8, 1986.
170 PEDIATRIC NEUROLOGY Vol. 2 No. 3
Figure 1. Case 1. Cranial CT depicting a large cisterna magna and cerebellar hypoplasia (left) and asymmetric ventricular dilatation (right).
mental delays. She did not crawl, pull to a stand, or walk. The patient was the product of a normal term pregnancy and an uneventful neonatal period. Hypopigmented skin lesions had been present at birth. The family history was not significant.
General physical examination was normal with the exception of the integument. Large areas of hypomelanosis involving the back and extremities were observed. There were no other skin lesions. Neurologic evaluation revealed mild hypotonicity without localizing neurologic signs. The Denver Developmental Screening Test in- dicated moderate gross motor delays, as well as mild delays in all other developmental parameters.
Basic laboratory studies and an electroencephalogram (EEG) were normal. A cranial CT revealed dilatation of the ventricular system and perimesencephalic cisterns reflecting minimal hypoplastic changes.
Case 4. A 3-month-old Navajo Indian child with normal perinatal history had been born with hypopigmented skin lesions involving the trunk and extremities. The family history was non- contributory.
Neurologic examination failed to reveal any localizing neurologic signs. The cranial nerves, cerebellar, sensory, and motor examinations were normal. Deep tendon responses were normoactive.
Basic laboratory studies and a cranial CT were normal. Formal neurodevelopmental evaluation at 26 months of age by the Central Arizona Child Evaluation Center revealed expressive and receptive language delays at approximately 12 and 6 months of age function, respectively. Overall cognitive function was at 18 months of age.
Discussion Hypomelanosis of Ito was described initially by Ito
[2] in 1952 as a unique cutaneous syndrome charac- terized by hypopigmented macules in marble, whorl, streak, or zig-zag patterns on the trunk and extremities. The lesions resembled the negative image of in- continentia pigmenti (IP) lesions so well that the
Figure 2. Case 2. Typical hypopigmented areas appear on the chest, neck, and buttocks.
Golden and Kaplan: Hypomelanosis o fho 171
Table 2. Neumlogic complications of hypomelanosis of ho
Case Age Sex
1 3 yrs F
2 9 yrs F
3 4 mos M
4 4 yrs F
5 3 yrs M
6 2 yrs F
7 2 yrs F
8 8 yrs F
9 20 mos F
10 15 yrs F
Neumlogic Findings
Strabismus
Developmental delay
Optic atrophy, hypotonicity
Seizures, strabismus
Focal seizures, abnormal EEG
Seizures
Seizures, ataxia
Focal seizures, asymmetric reflexes
Seizures, macrocephaly
Developmental delay
11 18 yrs M Seizures
CT
NT
NT
NT
NT
NT
NT
NT
NT
NT
NT
NT
Psychometric Tests
Normal
IQ71
Psychomotor delay
Normal
Normal
Normal
Normal, IQ94
Normal
Severe mental retardation
EMH
EMH
Reference
[9]
[10]
[7]
[3]
[6]
[11]
[12]
[131
[141
[141
(Continued next page)
syndrome initially was termed incontinentia pigmenti achromians. The HI skin lesions appear at, or shortly after, birth and then tend to darken and become less apparent over the ensuing months to years. The lesions may be unilateral or bilateral and appear anywhere on the body with the exception of the palms, soles, scalp, and mucous membranes. They are not preceded by any inflammatory, bullous, or verrucous phases in contrast to IP and are more easily identified with a Wood's lamp. The gross appearance of the skin lesions is sufficiently distinctive to be considered diagnostic [3]. Light microscopy of the skin lesions reveals decre*_sed numbers of pigment granules in melanocytes and keratinocytes, and occasionally an increased number of vacuolated cells in the epidermis. There are no pigmented macrophages in the dermis. Electron microscopy reveals a decreased number of mdanosomes within the melanocytes, as well as decreased melanin granules within the keratocytes [13].
The genetics of HI remain to be elucidated. Although a majority of the cases reported-are sporadic, several reports have documented familial occurrence consistent with autosomal dominant inheritance [4-6]. Recently, Miller et al. [3] reported the association of a chromosome abnormality consistent with a balanced translocation between chromo-~anes 2 and 8 (t 2,8) in a case of HI.
Approximately 60% of patients with HI have associated noncutaneous almormalities. Reviews by Buzas et al. [1] andJelnick et al. [7] on the spectrum of abnormalities in other organ systems have documented involvement of the eyes (e.g., strabismm, corneal opacities), musculoskeletal system (e.g., extremity hypertrophy or atrophy, fadal hemiatrophy, hyper- telorism, poorly formed ears), sweat glands (e.g., hypethydrosis of hypopigmented areas), teeth (e.g., dysplastic), breasts (e.g., hypoplasia), and hair (e.g., alopecia, hypertrichosis).
172 PEDIATRIC NEUROLOGY Vol. 2 No. 3
TaMe 2. Neumlogic complications ofhypomelanosis ofho (continued)
Neurologic
Case Age Sex Findings CT Psychometric Tests Reference
12 31A yrs M Seizures,
macrocephaly
13 10 yrs F Seizures
14 19 mos F Microcephaly,
nystagmus
15 10 yrs F Hypertelorism
16 13 yrs M Seizures,
abnormal EEG
17 21/2 yrs F Seizures,
abnormal EEG,
hemiplegia
18 22 mos M Seizures,
abnormal EEG,
macrocephaly
19 6 mos F Seizures,
abnormal EEG,
retinopathy,
chromosome abnormality
(t 2,8)
NT = Not tested
EMH = Educable mentally handicapped
NT Developmental [14]
delay
NT Developmental [14]
delay
NT Mental [14]
retardation
NT Psychomotor retardation [ 15 ]
Left frontal Mental retardation, [16]
atrophy IQ 54
Cerebral atrophy Severe mental [17]
porencephalic c y s t retardation
Normal Developmental delay [8]
(expired)
Left cerebral Severe developmental [3]
atrophy delay
The neurologic complications of HI (Table 2) in- clude: seizure disorders, mental retardation, psycho- motor delays, EEG abnormalities, focal and generalized cortical atrophies, pyramidal tract dysfunction, and gait disturbances. A recent neuropathologic study in a patient with HI revealed a neuronal migration defect with findings of heterotopias, altered neurons, and astrocytic giant cells. In view of these pathologic changes, a second trimester disorder of neural crest cell migration was suggested [8]. This disorder would account for the coexistence of CNS and skin pathology in HI cases.
Our patients confirm the high incidence of neurologic difficulties accompanying this neuro- cutaneous disorder. In addition, Case 1 documents another chromosomal aberration associated with HI. The authors stress the need for early recognition of this clinically identifiable disorder.
The authors gratefully acknowledge Rosalind Ruch and Barbara Bengtson who assisted in preparing the manuscript.
References [l] Buzas JW, Sina B, Burnett JW. Hypomelanosis of Ito. J Am
Acad Dermatol 1981;4:195-204. [2] Ito M. Studies of melanin. XI. Incontinentia pigmenti
achromians, a singular case of nevus depigmentosus systematicus bilateralis. Tohoku J Exp Med 1952; 55 (Suppl): 57-9.
[3] Miller CA, Parker WD. Hypomelanosis of lto: Association with a chromosomal abnormality. Neurology 1985;35:607-10.
[6] Cram DL, Fukuyama K. Society transactions: Unilateral systematized hypochromic nevus. Arch Dermatol 1974; 109:416.
[7] Jelinek JE, Bart RS, Schiff EM. Hypomelanosis of Ito ("in- continentia pigmenti achromians"). Arch Dermatol 1973; 107:596-601.
Golden and Kaplan: Hypomelanosis of Ito 17 3
[8] Ross DL, Liwnicz BH, Chun RW, Gilbert E. Hypomelanosis of Ito--a clinicopathologic study: Macrocephaly and gray matter heterotopias. Neurology 1982 ;32:1013-6.
