Int J Retina Vitreous 2017 18;3:34. Epub 2017 Sep 18.
Ocular Oncology Service, Suite 1440, Wills Eye Hospital, 840 Walnut Street, Philadelphia, PA 19107 USA.
Background: Incontinentia pigmenti is a rare X-linked dominant syndrome caused by mutation in the NEMO/IKKgamma gene, and characterized by a spectrum of cutaneous, ocular, neurologic and dental abnormalities. In the eye, findings include retinal vascular non-perfusion, occasionally with traction retinal detachment, retinal fibrosis, and retinal pigment epithelium defects. These findings can resemble retinoblastoma, especially when vitreoretinal fibrosis produces leukocoria. Read More
J Pediatr Health Care 2017 Sep 1. Epub 2017 Sep 1.
Incontinentia pigmenti is a rare neuroectodermal dysplasia caused by a defect in the IKBKG gene (formerly known as NEMO). There are 27.6 new cases per year worldwide; 65% to 75% are sporadic mutations, and 25% to 35% are familial. Read More
Incontinentia pigmenti (IP; Online Mendelian Inheritance in Man catalog #308300) is an X-linked dominant ectodermal disorder caused by mutations of the inhibitor of κ polypeptide gene enchancer in B cells, kinase γ (IKBKG)/ nuclear factor κB, essential modulator (NEMO) gene. Hemizygous IKBKG/NEMO loss-of-function (LoF) mutations are lethal in males, thus patients are female, and the disease is always transmitted from an IP-affected mother to her daughter. We present 2 families with father-to-daughter transmission of IP and provide for the first time molecular evidence that the combination of somatic and germ-line mosaicism for IKBKG/NEMO loss of function mutations in IP males resulted in the transmission of the disease to a female child. Read More
Incontinentia pigmenti (IP) is an X-linked genodermatosis affecting the skin and other sites, including the teeth, nails, hair, eyes and nervous system defects in female patients. Generally lethal in males, there are only a few known cases of males surviving this condition. Nuclear factor (NF)-κB essential modulator (NEMO), also known as inhibitor of kappa light polypeptide gene enhancer in B cells, kinase gamma (IKBKG), constitutes an essential activator of NF-κB. Read More
Open Access Maced J Med Sci 2017 Jul 23;5(4):501-505. Epub 2017 Jul 23.
Universitario di Ruolo, Dipartimento di Scienze Dermatologiche, Università degli Studi di Firenze, Facoltà di Medicina e Chirurgia, Dermatology, Via Vittoria Colonna 11, Rome 00186, Italy.
Incontinentia Pigmenti is an uncommon X-linked genodermatosis, caused by mutations in the NEMO gene. It is a systemic disease that involves tissue of ectodermic and mesodermic origin, including cutaneous tissue, teeth, eyes and the central nervous system, amongst other organs. The Authors report a rare case of Incontinentia Pigmenti in a female newborn. Read More
Incontinentia pigmenti (IP) is a uncommon gene disorder, heritage with X-linked dominant mode. IP patients have a characteristic dentition varying from marked hypodontia to delayed eruption and conical crowns on both dentitions. A 5½-year-old girl, whose mother and younger sister were also diagnosed with IP, has the whirling-like pigmented skin lesion over her trunk and four extremities. Read More
Department of Pediatric Radiology, Hôpital Necker Enfants Malades, AP-HP, 149 rue de Sèvres, 75105 Paris, France; INSERM U1000, 149 rue de Sèvres, 75015 Paris, France; UMR 1163, Institut Imagine, 24 boulevard du Montparnasse, 75015 Paris, France; University René Descartes, PRES Sorbonne Paris Cité, 12 rue de l'Ecole de Médecine, Paris, France.
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. Read More
Purpose: Anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) is caused by mutations in the NF-κB essential modulator (NEMO) or NF-κB inhibitor, alpha (IKBA) genes. A heterozygous NEMO mutation causes incontinentia pigmenti (IP) in females, while a hemizygous hypomorphic mutation of NEMO causes EDA-ID in males. In general, immunodeficiency is not shown in IP patients. Read More
Department of Research, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation; Department of Laboratory Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung; General Education Center, Tzu Chi University of Science and Technology, Hualien, Taiwan.
Incontinentia pigmenti (IP) is a rare disease with multisystemic anomalies, which commonly presents just after birth. Here, we report a rare case of IP patient with vitreous hemorrhage in school-age children. Therefore, physicians have to be alert and evaluate IP patients at all ages. Read More
Objective: Incontinentia pigmenti (IP) is a genetic disease leading to severe neurological symptoms, such as epileptic seizures, but no specific treatment is available. IP is caused by pathogenic variants that inactivate the Nemo gene. Replacing Nemo through gene therapy might provide therapeutic benefits. Read More
Ther Clin Risk Manag 2017 9;13:629-634. Epub 2017 May 9.
Division of Genetics, Department of Pediatrics, King Abdullah International Medical Research Centre, King Saud bin Abdulaziz Uiversity for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (NGHA), Riyadh, Saudi Arabia.
Incontinentia pigmenti (IP; Bloch-Sulzberger syndrome) is a rare, genetic syndrome inherited as an X-linked dominant trait. It primarily affects female infants and is lethal in the majority of males during fetal life. The clinical findings include skin lesions, developmental defects, and defects of the eyes, teeth, skeletal system, and central nervous system. Read More
Familiar genetic disorders such as neurofibromatosis type I (NF1), tuberous sclerosis complex (TSC), oculocutaneous albinism (OCA), basal cell nevus syndrome (BCNS), incontinentia pigmenti, ichthyosis, and epidermolysis bullosa (EB) have prominent, cutaneous manifestations. This review describes recent advances in knowledge concerning the pathophysiology, diagnosis, and treatment of these skin features. Specifically, clinical diagnostic criteria for incontinentia pigmenti, ichthyosis, and tuberous sclerosis have been updated. Read More
We report the case of a 17-year-old girl with incontinentia pigmenti who developed multiple large hyperkeratotic tumors within Blaschkoid hyperpigmented patches on her left leg. Biopsy demonstrated an endoexophytic nodule with irregular invaginations of keratinizing squamous epithelium and a central keratin-filled crater, consistent with keratoacanthoma-like lesions of incontinentia pigmenti. The tumors were successfully treated with intralesional methotrexate. Read More
Background: Incontinentia pigmenti (IP; MIM308300) is a severe, male-lethal, X-linked, dominant genodermatosis resulting from loss-of-function mutations in the IKBKG gene encoding nuclear factor κB (NF-κB) essential modulator (NEMO; the regulatory subunit of the IκB kinase [IKK] complex). In 80% of cases of IP, the deletion of exons 4 to 10 leads to the absence of NEMO and total inhibition of NF-κB signaling. Here we describe a new IKBKG mutation responsible for IP resulting in an inactive truncated form of NEMO. Read More
Cutaneous adverse drug reactions are among the most common noninfectious rashes of childhood. Cutaneous adverse drug reactions are classified as morbilliform, urticarial, bullous, pustular, or psoriasiform. Atopic dermatitis is one of the most common inflammatory cutaneous eruptions, and is characterized by pruritus and flexural distribution. Read More
Incontinentia pigmenti is a rare inherited disorder involving abnormalities of the skin, hair, eyes, musculoskeletal system, central nervous system, and the teeth. Dental abnormalities are the most common manifestations of this disorder. The purpose of this case report was to present the clinical and radiological findings of a seven-year-old girl as well as the results of her five-year follow up. Read More
Intellectual disability (ID), a common neurodevelopmental disorder characterized by limitations of both intellectual functioning and adaptive behavior, affects an estimated 1-2% of children. Genetic causes of ID are often accompanied by recognizable syndromal patterns. The vision apparatus is a sensory extension of the brain, and individuals with intellectual disabilities frequently have coexisting abnormalities of ocular structures and the visual pathway system. Read More
*Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina; and †Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, North Carolina.
Purpose: This report aims at expanding the current knowledge of retinal microanatomy in children with incontinentia pigmenti using hand-held spectral domain optical coherence tomography (SDOCT).
Methods: We reviewed OCT scans from 7 children (4 weeks-13 years) obtained either in the clinic or during an examination under anesthesia. The scans were analyzed for anatomical changes in the outer and inner retina, by certified graders. Read More
Stroke 2017 Feb 12;48(2):520-527. Epub 2017 Jan 12.
From the Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Germany (K.M., M.S.); INSERM U1038/BIG, CEA, Grenoble, France (G.C.); and Institute of Genetics and Biophysics, "Adriano Buzzati-Traverso", IGB-CNR, Naples, Italy (M.V.U.).
Objectives: Current knowledge on dental anomalies in patients with incontinentia pigmenti (IP) has been obtained by examining case reports; however, an overall characterization of such alterations remains lacking. The objective of this study was to determine the frequency, type and location of dental alterations in IP using a case series.
Methods: Fourteen patients (9 children and 5 adults) with a clinical diagnosis of IP who presented dental anomalies were included in this study. Read More
Linear vesicles or papules in a newborn can be a presenting sign of incontinentia pigmenti (IP). In this report, we present two cases of neonates with cutaneous manifestations of incontinentia pigmenti. In one case, mild peripheral eosinophilia was noted. Read More
Incontinentia pigmenti is a rare genodermatosis in which the skin involvement occurs in all patients. Additionally, other ectodermal tissues may be affected such as the central nervous system, eyes, hair, nails and teeth. The disease has an X-linked dominant inheritance pattern. Read More
Faculty of Health Sciences, Division of Chemical Systems and Synthetic Biology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Anzio Road, Observatory, Cape Town, Western Cape 7925, South Africa.
The NF-κB pathway has critical roles in cancer, immunity and inflammatory responses. Understanding the mechanism(s) by which mutations in genes involved in the pathway cause disease has provided valuable insight into its regulation, yet many aspects remain unexplained. Several lines of evidence have led to the hypothesis that the regulatory/sensor protein NEMO acts as a biological binary switch. Read More
Sweating is regulated by various neurohormonal mechanisms. A disorder in any part of the sweating regulatory pathways, such as the thermal center, neurotransmitters in the central to peripheral nerve, innervation of periglandular neurotransmission, and sweat secretion in the sweat gland itself, induces dyshidrosis. Therefore, hereditary disorders with dyshidrosis result from a variety of causes. Read More
In this article we present the case of a 2-day-old newborn girl in good general condition, with herpetic arranged pustules on the skin of her whole body. The case highlights the importance of a detailed diagnostic workup for newborns with pustular skin disease. Especially to differentiate between the diagnosis of incontinentia pigmenti and a congenital herpes infection. Read More
Incontinentia Pigmenti (IP) is a rare X-linked disease characterized by early male lethality and multiple abnormalities in heterozygous females. IP is caused by NF-κB essential modulator (NEMO) mutations. The current mechanistic model suggests that NEMO functions as a crucial component mediating the recruitment of the IκB-kinase (IKK) complex to tumor necrosis factor receptor 1 (TNF-R1), thus allowing activation of the pro-survival NF-κB response. Read More
Purpose: To describe a case of incontinentia pigmenti with proliferative retinopathy successfully treated by combination of repeated retinal laser photocoagulation and intravitreal ranibizumab injection.
Methods: Single interventional case report of a 4-year-old girl, known case of incontientia pigmenti, first screened at the age of two, presented with proliferative retinopathy. Sole treatment by panretinal laser photocoagulation failed to control the progression of retinal neovascularization. Read More
The transcription factor NF-κB is central to numerous physiologic processes including bone development, and its activation is controlled by IKKγ (also called NEMO), the regulatory subunit of IKK complex. NEMO is X-linked, and mutations in this gene result in Incontinentia Pigmenti in human hemizygous females. In mice, global deficiency causes embryonic lethality. Read More
Division of Neuroradiology, Russell H. Morgan Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:
Neurocutaneous syndromes (or phakomatoses) are a diverse group of congenital disorders that encompass abnormalities of neuroectodermal and, sometimes, mesodermal development, hence commonly involving the skin, eye, and central nervous system. These are often inherited conditions and typically present in early childhood or adolescence. Some of the abnormalities and clinical symptoms may, however, be progressive, and there is an increased risk of neoplastic formation in many of the syndromes. Read More
Incontinentia pigmenti (IP) is an X-linked dominant disorder that in most cases is considered lethal in males. IP affects the skin, hair, teeth, nails, eyes, and central nervous system. We report a case of persistent hypercalcemia (10. Read More
Late recurrences of first-stage inflammatory vesiculobullous lesions of incontinentia pigmenti (IP) are uncommon but have been reported to occur in the setting of infections, fevers, and vaccinations. This phenomenon has not been described in the setting of atypical hand, foot, and mouth disease (HFMD). In addition, atypical HFMD often has a predilection for areas of previous inflammation or trauma, such as areas of atopic dermatitis (eczema coxsackium). Read More
Incontinentia Pigmenti (IP, OMIM#308300) is a rare X-linked genomic disorder (about 1,400 cases) that affects the neuroectodermal tissue and Central Nervous System (CNS). The objective of this study was to describe the cognitive-behavioural profile in children in order to plan a clinical intervention to improve their quality of life. A total of 14 girls (age range: from 1 year and 2 months to 12 years and 10 months) with IP and the IKBKG/NEMO gene deletion were submitted to a cognitive assessment including intelligence scales, language and visuo-spatial competence tests, learning ability tests, and a behavioural assessment. Read More
We present a 12-month-old Hispanic female with a reticulated, hyperchromic rash in a striated pattern appearing on upper and lower extremities and trunk and back since the age of 6 weeks. Over the next 10 months, the rash persisted. The rash did not respond to treatment with antifungals and steroids. Read More
We report the case of an infant girl with incontinentia pigmenti (IP) complicated by fatal pulmonary arterial hypertension (PAH). She was diagnosed with IP, based on the presence of specific skin lesions, neonatal seizures, hypereosinophilia and a maternal family history of IP. At the age of 2 months, she was diagnosed with PAH on systolic heart murmur due to tricuspid valve regurgitation. Read More
EMBO Mol Med 2016 06 1;8(6):609-25. Epub 2016 Jun 1.
Hubertus Wald Cancer Center, Department of Oncology and Hematology University Medical Center Hamburg-Eppendorf, Hamburg, Germany Department of Hematology and Oncology, Augsburg Medical Center, Augsburg, Germany
Gene therapy critically relies on vectors that combine high transduction efficiency with a high degree of target specificity and that can be administered through a safe intravenous route. The lack of suitable vectors, especially for gene therapy of brain disorders, represents a major obstacle. Therefore, we applied an in vivo screening system of random ligand libraries displayed on adeno-associated viral capsids to select brain-targeted vectors for the treatment of neurovascular diseases. Read More
Aim: To report on the neurological presentation and neuroimaging findings in newborn infants with incontinentia pigmenti.
Method: The clinical and neurological course including neuroimaging and follow-up data of eight newborn infants with the neurological phenotype of incontinentia pigmenti were retrospectively reviewed.
Results: While the clinical picture was polymorphic, the neurological manifestations were defined as encephalopathic and comprised lethargy and seizures in all but one of the infants. Read More
Introduction: Incontinentia pigmenti (IP) is a rare X-linked dominant genodermatosis. Mutations of the IKBKG gene are responsible for IP. A deletion of exons 4-10 can be found in 80% of patients with IP. Read More
Clin Immunol 2016 Mar 23;164:52-6. Epub 2016 Jan 23.
Center of Chronic Immunodeficiency, University Medical Center Freiburg, Germany; Center for Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Germany. Electronic address:
NF-κB essential modulator (NEMO) deficiency causes ectodermal dysplasia with immunodeficiency in males, while manifesting as incontinentia pigmenti in heterozygous females. We report a family with NEMO deficiency, in which a female carrier displayed skewed X-inactivation favoring the mutant NEMO allele associated with symptoms of Behçet's disease. Hematopoietic stem cell transplantation of an affected boy from this donor reconstituted an immune system with retained skewed X-inactivation. Read More
Background: Incontinentia pigmenti is a rare neurocutaneous disorder that may result in neurological symptoms in addition to its characteristic skin rashes. The pathogenesis of central nervous system disorders in incontinentia pigmenti remains unclear, but it has been suggested that vascular abnormalities and inflammatory processes may play important roles. Notably, there is no established treatment for central nervous system disorders in incontinentia pigmenti. Read More
Background: Incontinentia pigmenti is a rare X-linked neurocutaneous disorder that can present in the neonatal period with seizures and encephalopathy. Brain magnetic resonance imaging and magnetic resonance angiography may reveal cerebral infarction and arteriopathy.
Patient Description: We describe a neonate with the typical rash of incontinentia pigmenti along with seizures and brain magnetic resonance imaging abnormalities. Read More