Incontinentia pigmenti: clinical and neuroradiologic features

doi:10.1016/0387-7604(93)90122-O

Brain and Development

Volume 15, Issue 5, September 1993, Pages 362-366

https://doi.org/10.1016/0387-7604(93)90122-O Get rights and content

Abstract

Developmental brain malformations and destructive processes of unknown etiology were described in incontinentia pigmenti (IP). Two patients, a male and a female, with characteristic skin lesions and central nervous system (CNS) involvement are reported. Neuroradiological examinations revealed hypoplasia of corpus callosum, neuronal heterotopias, and periventricular white matter damage. No specific infectious, inflammatory, or metabolic abnormalities were identified. These neuroradiographic findings may suggest that an ischemic pathogenetic mechanism occurred prenatally. We speculate that the brain damage in IP may occur during CNS development and in successive stages. Magnetic resonance imaging appears more useful to detect white matter lesions and brain malformations in patients with IP.

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Cited by (38)

Severe neuroimaging anomalies are usually associated with random X inactivation in leucocytes circulating DNA in X-linked dominant Incontinentia Pigmenti
2017, Molecular Genetics and Metabolism
Citation Excerpt :
While several studies have reported abnormal brain MRIs in IP patients, the present study reports what we believe to be the first evidence of a correlation between severe neurological/brain MRI anomalies and a random pattern of chromosome X inactivation in IP. The most frequent brain MRI anomalies reported to date included white matter T2-weighted hyper-signals and mild cortical and corpus callosum atrophy [2,12–15]. Several authors also reported on ischemic and hemorrhagic diffuse lesions, always in neonates [13,16,17].
Incontinentia Pigmenti (IP) is a skin disorder with neurological impairment in 30% of cases. The most common disease causing mutation is a deletion of exons 4-10 of the IKBKG gene, located on chromosome Xq28, with skewed X-chromosome inactivation in females, but few cases of random X-inactivation have been reported. We have correlated brain anomalies with X-chromosome inactivation status determined on leucocytes circulating DNA. We reviewed MRI of 18 girls with genetically proven IP. We found three patterns of MRI, normal MRI (n = 5), mild white matter abnormalities with cortical and corpus callosum atrophy (n = 6), and severe cortical abnormalities suggesting a vascular disease (n = 7). Most patients with severe abnormalities had random X-inactivation (6/7,86%), while 80% (4/5) of patients with normal MRI and 100% (6/6) of patients with mild white matter abnormalities had skewed inactivation. These results suggest that skewed chromosome X-inactivation may protect brain from damage, while in case of random inactivation, expression of the mutated IKBKG gene may lead to severe brain lesions.
Incontinentia pigmenti
2015, Piel
Neurological findings in incontinentia pigmenti; a review
2012, European Journal of Medical Genetics
Citation Excerpt :
Signs of conjunctivitis were found in 2 patients [29, 33]. Finally, cataract was described in 1 patient [34]. Most patients with ophthalmological manifestations also have brain abnormalities at MRI (Table 3).
Incontinentia Pigmenti is a rare X-linked multisystem disorder with well described and pathognomonic skin manifestations. Neurological manifestations are found in 30% of IP patients, forming one of the major causes of morbidity and mortality of the condition. In this review, clinical and brain imaging data of 45 IP patients with a neurological phenotype are reviewed. Several clinical presentations could be identified, comprising seizures, infantile encephalopathy, acute disseminated encephalomyelitis and ischemic stroke. Most neurological features presented during the neonatal period. No patients presented during adolescence or at adult age. Seizures of different type are reported in about 20% of the patients at young age and seem to correlate with the degree of cerebrovascular damage. Brain MRI findings include periventricular and subcortical white matter disease, haemorrhagic changes, corpus callosum hypoplasia, cerebral atrophy and cerebellar hypoplasia. Ocular findings comprise a range of retinal vascular changes and optic atrophy, but also developmental defects like microphthalmia and cataract. Most findings may reflect changes following brain injury. Both (ischemic) vascular and inflammatory components may play a role in the cerebral and ocular phenotype. However, a role of disturbed apoptosis during development may also be a contributing factor.
Acute disseminated encephalomyelitis in an infant with incontinentia pigmenti
2009, Brain and Development
We report the case of a female Japanese infant who was diagnosed with incontinentia pigmenti (IP) on the basis of the clinical and pathological findings of characteristic skin lesions and the detection of deletion in the nuclear factor-kappa B essential modulator gene at Xq28. The patient developed repetitive seizures at the age of 7 months when she was diagnosed with acute disseminated encephalomyelitis (ADEM), an inflammatory demyelinating disease of the central nervous system that often occurs after vaccination or infection. The causative infectious agent in this patient seemed to be Mycoplasma pneumoniae because of the increased titer of its serum antibody and the detection of its DNA in the initial cerebrospinal fluid sample. This patient showed significant improvement on receiving immunosuppressive therapy with corticosteroids. This is the second case report presenting an IP patient susceptible to ADEM, and therefore, ADEM should be considered early in the differential diagnosis of acute neurological illness for IP patients.
Extensive cerebral infarction in the newborn due to incontinentia pigmenti
2008, European Journal of Paediatric Neurology
Incontinentia pigmenti (IP) is a rare X-linked dominant neuroectodermal multisystem disorder characterized by skin lesions following Blaschko lines. In almost all patients the skin is involved and in 30–50% the central nervous system (CNS) is. Vascular occlusive phenomena probably play a role in CNS involvement. Whether these vascular changes are based on macro- or microvascular disease in the neonatal presentation is not fully understood.
We describe two patients with IP with neonatal seizures related to cerebral infarction. In comparison, we reviewed reports of ischaemic cerebrovascular injury in neonatal IP.
No descriptions of documented large artery occlusion in neonatal IP was found in the literature. One of our patients showed striatal arteriopathy, never described before in IP. Extensive injury in one of our cases was heterogeneous, mixing healthy with diseased areas within large arterial fields.
We postulate that neonatal cerebral infarction in IP is a macrovascular disorder of medium sized or small arteries. The pattern of arterial involvement might follow hypothetical brain Blaschko lines. The extent of cerebral involvement probably results from genetic mosaicism in which Lyonisation leads to endothelial apoptosis, similar to the process in the skin.
Abnormal White Matter in a Neurologically Intact Child With Incontinentia Pigmenti
2007, Pediatric Neurology
Citation Excerpt :
Hypoplasia and agenesis of the corpus callosum are often observed [6-8]. White matter abnormalities, primarily hyperintensity on T2 magnetic resonance imaging, have been reported [4,6-8]. In almost all cases, imaging abnormalities correlated with clinical neurologic abnormalities: seizures, mental retardation, and hemiparesis.
Incontinentia pigmenti is an X-linked neurocutaneous disorder which is often lethal in males. Ectodermal tissues are involved, and affected females often have abnormalities of skin, teeth, hair, eyes, and the central nervous system. Central nervous system involvement ranges from none to multiple strokes, seizures, and mental retardation. Deletions in the nuclear factor kappa β essential modulator gene at Xq28 are present in 70-80% of patients with incontinentia pigmenti. White matter abnormalities have been reported in females with significant neurologic involvement. This report describes a neurologically intact child with deletion positive incontinentia pigmenti with significant white matter involvement, broadening the scope of this finding in incontinentia pigmenti.

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Incontinentia pigmenti: clinical and neuroradiologic features

Abstract

Pediatr Neurol

Peculiar pigmentation of the skin in an infant

Trans Clin Soc London

Eigentümliche bisher nicht beschriebene Pigmentaffektion

Schweiz Med Wochenschr

Uber eine bisher nicht beschriebene congenitale Pigmentanomalie

Arch Dermatol Syph

Incontinentia pigmenti: a world statistical analysis

Arch Dermatol

Incontinentia pigmenti

Neurol Clin

Incontinentia pigmenti

Am J Dis Child

Bloch-Sulzberger syndrome (incontinentia pigmenti): report of a case with prominent neurological features

Arch Neurol

Computed tomographic demonstration of brain changes in incontinentia pigmenti

Am J Dis Child

Incontinentia pigmenti in identical twins with separate skin and neurological disorders

Acta Dermatol Venereol

Sindrome di Bloch-Sulzeberger ed epilessia

Boll Lega It Epil