Ito's hypomelanosis (incontinentia pigmenti achromians)

Ito's hypomelanosis (incontinentia pigmenti achromians)

Ito’s hypomelanosis (incontinentia pigmenti achromians) A review of four cases P. Fleury*, K. Dingemans* *, W.P. de Groat* * *, A.P. Oranje* * * * *, ...

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Ito’s hypomelanosis (incontinentia pigmenti achromians) A review of four cases P. Fleury*, K. Dingemans* *, W.P. de Groat* * *, A.P. Oranje* * * * *, P.A. VoOte* * * * * *, M.J. Woerdeman* * *, J.W. Delleman* * * * * * *, J.W.E. Oorthuys* * * *, and A.J. Verboom * * * * * *

Introduction In 1952 Ito described the occurrence of a bilateral systematized depigmented nevus in a 22-year-old Japanese woman’. He used the term incontinentia pigmenti achromians because the configuration of the leukoderma seemed to appear as the negative picture of hype~pigmentation as seen in dassical incontinentia pigmenti or Bloch-Sulzberger syndrome. Since then 61 other cases have been reported2-45. Among those 61 reported cases 16 are negroes, 12 Japanese and 13 other patients are coioured patients too. 1.5patients are European and the colour is not mentioned in 4 cases. About 10 other cases are reported46-5Z. The condition has been described under various designations such as systematized hypochromic nevus, Ito syndrome, Ito’s disease and Ito’s hypomelanosis. These differences in nomenclature create confusion. Because of the resemblance of the names this syndrome is easily mistaken for incontinentia pigmenti, a syndrome described in a l-year-old girl in 1926 by Blochs3 and in 1928 by Sulzbergers4. The cutaneous signs in both pigmentary disturbances are completely different. Yet some difficulties in the diagnosis are mentioned by Pinol et al.43, Mital et al. ss and Wiley et al. 56

Summary In 1952 Ito described the occurrence of a bilateral systematized depigmented nevus in a 22-year-old Japanese woman. He used the term incontinentia pigmenti achromians. The condition has been described under various designations, such as for instance Ito’s hypomelanosis. Till now 71 patients with this syndrome are described. We will report 4 cases, 2 boys and 2 girls, 2 Caucasian, 1 Indonesian and 1 Caribean child. The cutaneous signs in these 4 patients fit in with the syndrome of Ito’s hypomelanosis. Of these 4 children 3 are mentally retarded, 2 have epilepsy. Congenital malformations are seen in 3 children. Electronmicroscopy of skin biopsies of the hypomelanotic nevus and of the normal skin were performed. In the biopsy of the normal skin of one patient interruption of the basement membrane is seen. Anomalies of the central nervous system as seen in our patients occur in about 40% of the cases. Abnormalities of skin derivatives next to other ectodermal anomalies are described. Affection of other germ layers also occur to a varying degree. In our 4 patients some of these abnormalities exist also. These 4 cases are presented to underline the fact that this syndrome seems not to be as extremely rare as is proposed. Key words: Ito’s hypomelanosis, neous syndrome.


‘Department of Neurology, * *Pathologic Anatomy, * * ‘Department of Dermatology, Free University, Amsterdam, * * * *Department of Pediatrics, Academic Medical Centre, Amsterdam, * * * * * Department of Dermatology, Sophia Kinderziekenhuis. Rotterdam, * * * * * ‘Emma Kinderziekenhuis, Amsterdam, * * * * * * * Interuniversity Ophthalmological Research Institute, Amsterdam, The Netherlands. Address for correspondence and reprint requests: P. Flew-y, Department of Neurology, Academic Medical Centre, Meibergdreef 9, 110.5 AZ Amsterdam, The Nether~an~. Accepted 6.12.85 Clin Neurol Neurosurg 1986, Vol. 88-1.


Fig. 1 Hypomelanosis of the trunk of case Lseen by daylight (A) and with Wood‘s light i.e. U.V. light with 366 nm wave lenghth (B)

Case reports Case I A Z-year-old Dutch boy was seen because of epilepsy, h~drocephalus, mental retardation and generalized hypotonia. He is the second child of healthy non-consanguineous parents. Neither the parents nor the healthy older brother, nor an epileptic niece on the mother’s side showed pigment disturbances of the skin when examined in daylight or with ultraviolet light with 366 nm wavelength (Wood’s light). Examination of the patient revealed linear and whorling hypopigmented areas on the anterior and posterior aspects of the trunk and all extremities. The pattern was marble-cake and more pronounced on examination by Wood’s light (Fig. la, b). There was no preceding skin inflammation. The cutaneous features were probably already present at birth.

Fig. 2 Irregular placed, cone shaped teeth of case 1. The left lateral maxillary incisor shows an anomaly of the enamel.


Associated abnormalities seen in this patient are: irregularly placed cone shaped teeth with an enamel defect of one deciduous incisor (Fig. 2), gingival hyperplasia not due to the use of phenytoin, hyperteIorism, antimongoloid slant of the palpebral fissures and more anomalies of the skeletal system, cryptorchidism and micropenis. Ophthalmologic examination revealed convergent strabismus with uncoordinated eyemovements, tunica vasculosa and a persistent hyaloid artery. Case 2 A l-year-old Indonesian boy was seen because of mental retardation without indicative cause, generalized hy~tonia and nystagmus. Since birth pigmentary shifting exists all over the body consisting of swirly hypopigmentations, especially on the posterior parts of the trunk and on the flexor sides of the legs (Fig. 3).

Fig. 3 The leg of the Indonesian boy with Ito’s hypomelanosis.

Fig. 4 Asymmetric development of the mammae with the characteristic pigment disturbance of Ito’s hypomelanosis in the configuration of whorls and streaks in case 3.

Fig. 5 The back side of the legs of the Caribean girl with Ito’s hypomelanosis.

These pigmentary disturbances are more evident on examination with Wood’s light. Pregnancy and birth were uncomplicated. In the family there are no points of contact indicating a hereditary disorder except that an older sister which we could not examine has some hyperpigmented macules. His mother only has a cafe-au-lait spot even when examined with Wood’s light. No preceding skin inflammation is mentioned in this patient. Further ophthalmologic examination revealed white round spots in the irides, which are not seen in the mother or the grandmother. These spots are mentioned also by Hamade et aL2 and by Pinol et al.43. The EEG showed focal theta and delta waves indicative of a defect in the left temporal region.

lanotic streaks at the back side of both legs were seen (Fig. 5). Wood’s light did not bring out these pigmentary disturbances more clearly. Associated abnormalities seen in this patient are macroglossia, diastasis of the musculi recti abdomini and hyperplasia of the upper pool of the left kidney. The last abnormality is described in Ito’s hypomelanosis by Rubinzs. We were not able to examine the parents.

Case 3 A 13-year-old Dutch girl showed asymmetric development of the mammae as described by Ito’ and in 2 other cases 22,50,besides the characteristic pigment disturbances in the configuration of whorls and streaks (Fig. 4). The EEG showed atypical abnormalities. There was no abnormality in the parents. Unusual pigmentary variation in the skin of any member of the family is not known to her. Case 4 A 2-year-old Caribean girl was seen because of progressive hydrocephalus, mental retardation and epileptic fits. On the left part of the trunk and the left arm hypomelanosis in the configuration of streaks developed in the first year of life. Later hypome-

Electronmicroscopic studies of hypomelanotic and normal skin areas Abnormalities of melanocytes3~5~20~22~25~28~30~37~57 or Langerhans [email protected]~37 are not observed. Only in one case a single nerve ending was noticed at the epidermal-dermal junction. Following the description of Morohashi et al.** one of us (K.D.) looked for this abnormality very intensively. Disturbance of keratinization or malformation of skin appendages are not seen either. In the first case an interruption of the basement membrane in the normal pigmented skin is seen (Fig. 6). In the hypomelanotic area small giant cells are seen in the epidermis. These abnormalities were not observed in the other cases despite intensive investigation. Discussion The cutaneous signs in these four patients fit in with the syndrome of Ito’s hypomelanosis. This is a neurocutaneous syndrome. Anomalies of the central nervous system occur in about 40% of the [email protected], especially men41

Fig. 6

Detail of

the dermauepidermal


tion in a biopsy of the normal pigmented skin of case

At the


right side of the micrograFh,

the basal parts of several keratinocytes, characterized electron-dense

by the prescncc of tonofilamenta,


outlined by an almost continuous basal lamina. The left side show\ a portion of a large, relatively protruding king

empty ccl1

into the dermis

a basal lamina.

and lac-




tal retardation,

epilepsy, generalized hypotoor pyramidal signs 7.1~37 and hydrocephalus24.25.26,X, macrocephalyJ4 or microcephalyY,15.“. CT-scan abnormalities were noted, like low density of the whole white matter of the cerebral hemispheres3*, focal cerebral atrophy17, or brain deformities which were consistent with hamartomas or heterotopias”. Systematized linear and patchy depigmentations, distributed in a pattern following the lines of Blaschko3815X,but also swirly hypopigmentations with the configurations of whorls are characteristic. These pigmentary disturbances develop in the first years of life and fade in the second decade. Abnormalities of skin derivatives i.e. naijsZ.S.22.Zh.39, hair2.39.40 and sweat glands ‘.r’.7~2s are described next to other ectodermal anomalies of breaStS’.22.“” teeth6.18&“5,~? and nia17.24,29.32.W,37.42.#,






genie disorders a predilection for a given germinal layer exists, but affection of other germ layers also occur to a varying degree. Very different anomalies of the skeletal system are described and finally abnormality of one kidney is mentioned in three casess~Li~42. The deviations of the cell morphological aspects demonstrated by some investigators by consisnot studies are ultrastructural tentij.ih.‘7.4i.42.S~. Neither the meaning of these findings, nor the abnormality we noticed in one of our cases is clear. 42

The ratio of female:male patients with Ito’s hypomelanosis is 2: 1. Autosomal dominant inheritance is described in 22b.2y and possibly in 33yfamilies. This mode of inheritance may occur more frequently than presumed. First of all most of the authors restrict themselves by describing the pigmentary disorder of the patient without mentioning history or examination of family members. Secondly in moderately pigmented people hypopigmentation might be overlooked. Finally according to some authors the areas of hypopigmentation become smaller in the sccond decade of life2L,ZN.3’. Consanguinity of the parents of 3 patients is also describedh,‘“-“‘, while Grosshans et ~1.~’ described three sisters with Ito’s hypomelanosis and one sister of a case described by Schwartz et at.” showed hypopigmented spots. Most of the patients are sporadic cases. In fact little can be concluded about the genetic aspects of Ito’s hypomelanosis. Chromosomal abnormalities are described in 1 sporadic case’. Although it is very likely that Ito’s hypomelanosis is a nosological entity, this thesisstill has to be proven. If it is an entity, hereditary aspects which are important for genetic counseling can be studied more effectively.

Incontinentia pigmenti achromians. Multiple cases within a family. Arch Derm 1972; 105:424-5. RUBIN MB.

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