Recurrent sterile abscesses in a case of X-linked neutropenia.

Cutaneous manifestations are common in monogenic immune disorders, including both infectious and non-infectious etiologies. We report follow-up of a case initially published in Pediatric Dermatology in 2001 of a 13-year-old boy with a history of inflammatory skin lesions and neutropenia who developed neutrophilic dermatoses precipitated by G-CSF. Whole exome sequencing performed at 36 years of age revealed a gain-of-function mutation in the WAS gene, leading to a diagnosis of X-linked neutropenia.

Recessive Mutations in AP1B1 Cause Ichthyosis, Deafness, and Photophobia.

We describe unrelated individuals with ichthyosis, failure to thrive, thrombocytopenia, photophobia, and progressive hearing loss. Each have bi-allelic mutations in AP1B1, the gene encoding the β subunit of heterotetrameric adaptor protein 1 (AP-1) complexes, which mediate endomembrane polarization, sorting, and transport. In affected keratinocytes the AP-1 β subunit is lost, and the γ subunit is greatly reduced, demonstrating destabilization of the AP-1 complex.

The importance of considering monogenic causes of autoimmunity: A somatic mutation in KRAS causing pediatric Rosai-Dorfman syndrome and systemic lupus erythematosus.

Objectives: Clinicians need to be aware of the growing list of defined monogenic etiologies of autoimmune diseases. This is particularly relevant when evaluating children, as these rare monogenic forms of autoimmunity tend to present very early in life.

Methods And Results: By harnessing the transformative power of next generation sequencing, we made the unifying diagnosis of RAS-associated autoimmune leukoproliferative disease (RALD), caused by the somatic gain-of-function p.

Vascular Anomalies Classification: Recommendations From the International Society for the Study of Vascular Anomalies.

Vascular anomalies represent a spectrum of disorders from a simple "birthmark" to life- threatening entities. Incorrect nomenclature and misdiagnoses are commonly experienced by patients with these anomalies. Accurate diagnosis is crucial for appropriate evaluation and management, often requiring multidisciplinary specialists.

Successful approach to treatment of Helicobacter bilis infection in X-linked agammaglobulinemia.

Helicobacter bilis, an unusual cause of chronic infections in patients with X-linked agammaglobulinemia (XLA), is notoriously difficult to diagnose and eradicate. Based on the limited number of cases reported worldwide, we highlight the typical features of H. bilis infection in XLA and provide a rational and successful approach to diagnosis and treatment of this challenging infection.

Use of propranolol in treating hemangiomas.

Question: I see many children with infantile hemangiomas and have read about new therapeutic options such as propranolol. Is this medication effective and safe for treating hemangiomas in children?

Answer: Most infantile hemangiomas resolve spontaneously without any need for therapy. In many case series, propranolol has been shown to be effective and safe in treating hemangiomas that cause complications.

Intracerebral large artery disease in Aicardi-Goutières syndrome implicates SAMHD1 in vascular homeostasis.

Aim: To describe a spectrum of intracerebral large artery disease in Aicardi-Goutières syndrome (AGS) associated with mutations in the AGS5 gene SAMHD1.

Method: We used clinical and radiological description and molecular analysis.

Results: Five individuals (three males, two females) were identified as having biallelic mutations in SAMHD1 and a cerebral arteriopathy in association with peripheral vessel involvement resulting in chilblains and ischaemic ulceration.

Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response.

Aicardi-Goutières syndrome is a mendelian mimic of congenital infection and also shows overlap with systemic lupus erythematosus at both a clinical and biochemical level. The recent identification of mutations in TREX1 and genes encoding the RNASEH2 complex and studies of the function of TREX1 in DNA metabolism have defined a previously unknown mechanism for the initiation of autoimmunity by interferon-stimulatory nucleic acid. Here we describe mutations in SAMHD1 as the cause of AGS at the AGS5 locus and present data to show that SAMHD1 may act as a negative regulator of the cell-intrinsic antiviral response.

Cystic bone lesions in a boy with Darier disease: a magnetic resonance imaging assessment.

We describe asymptomatic bone cysts in the right humerus of a 17-year-old boy with Darier disease. The cysts were found when a radiographic skeletal survey was performed to monitor for adverse effects of oral retinoid therapy. Magnetic resonance imaging was used to confirm that the lesions were cystic and to delineate their extent.

SLC29A3 gene is mutated in pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome and interacts with the insulin signaling pathway.

Pigmented hypertrichotic dermatosis with insulin-dependent diabetes (PHID) syndrome is a recently described autosomal recessive disorder associated with predominantly antibody negative, insulin-dependent diabetes mellitus. In order to identify the genetic basis of PHID and study its relationship with glucose metabolism, we performed homozygosity mapping in five unrelated families followed by candidate gene sequencing. Five loss-of-function mutations were identified in the SLC29A3 gene which encodes a member of a highly conserved protein family that transports nucleosides, nucleobases and nucleoside analogue drugs, hENT3.

Parkes Weber syndrome, vein of Galen aneurysmal malformation, and other fast-flow vascular anomalies are caused by RASA1 mutations.

Capillary malformation-arteriovenous malformation (CM-AVM) is a newly recognized autosomal dominant disorder, caused by mutations in the RASA1 gene in six families. Here we report 42 novel RASA1 mutations and the associated phenotype in 44 families. The penetrance and de novo occurrence were high.

A comparison of disease severity among affected male versus female patients with PHACE syndrome.

Background: PHACE syndrome (Online Mendelian Inheritance in Man database No. 606519) refers to the association of large, plaquelike, or segmental hemangiomas of the face, with one or more of the following anomalies: posterior fossa brain malformations, arterial cerebrovascular anomalies, cardiovascular anomalies, eye anomalies, and ventral developmental defects, specifically sternal defects, supraumbilical raphe, or both.

Objective: The underlying pathogenesis of PHACE is unknown.

Clinical and molecular phenotype of Aicardi-Goutieres syndrome.

Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-->5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease.

Pigmented hypertrichotic dermatosis and insulin dependent diabetes: manifestations of a unique genetic disorder?

A novel pigmented dermatosis was observed in four unrelated boys, three of whom had insulin-dependent diabetes. Three patients were the offspring of consanguineous parents. All four boys had pigmented hypertrichotic patches or induration on the upper inner thighs, with variable involvement of the genitalia, trunk, and limbs.

Keratosis pilaris rubra: a common but underrecognized condition.

Background: Keratosis pilaris is a common skin disorder of childhood that often improves with age. Less common variants of keratosis pilaris include keratosis pilaris atrophicans and atrophodermia vermiculata.

Observations: In this case series from dermatology practices in the United States, Canada, Israel, and Australia, the clinical characteristics of 27 patients with keratosis pilaris rubra are described.

Treatment of cystic lymphatic vascular malformations with OK-432 sclerotherapy.

Background: Cystic lymphatic vascular malformations are benign lesions that can cause disfigurement and functional impairment. Complete surgical resection is often difficult, and clinical recurrence is common. Sclerotherapy has been used as an alternative to excision.

Old challenges and new directions in pediatric rheumatology.

A symposium was convened April 2, 2005, by the Department of Pediatrics, University of British Columbia, Vancouver, Canada. The event was a tribute to Dr. Ross Petty on his retirement and in recognition of his contributions to the local and international community of pediatric rheumatology.

Cerebellar and cerebral atrophy in trichothiodystrophy.

Trichothiodystrophy is a rare neuroectodermal disorder of autosomal recessive inheritance that is characterized by brittle hair, nail dysplasia, ichthyosis, mental retardation, and gonadal failure. We describe a female patient whose cranial MRI revealed almost total lack of myelination in the supratentorial white matter, which is similar to the previously described cases. In addition, there was progressive cerebellar and cerebral atrophy, which has not been well documented in association with trichothiodystrophy.