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. All affected individuals presented multifocal capillary malformations (CMs), which represent the hallmark of the disorder. Importantly, one-third had fast-flow vascular lesions. Among them, we observed severe intracranial AVMs, including vein of Galen aneurysmal malformation, which were symptomatic at birth or during infancy, extracranial AVM of the face and extremities, and Parkes Weber syndrome (PKWS), previously considered sporadic and nongenetic. These fast-flow lesions can be differed from the other two genetic AVMs seen in hereditary hemorrhagic telangiectasia (HHT) and in phosphatase and tensin homolog (PTEN) hamartomatous tumor syndrome. Finally, some CM-AVM patients had neural tumors reminiscent of neurofibromatosis type 1 or 2. This is the first extensive study on the phenotypes associated with RASA1 mutations, and unravels their wide heterogeneity.

Our aim was to describe the types of psoriasis seen in a large series of patients presenting to a tertiary referral pediatric dermatology department using a classification system combining conventional terminology and additional categories based on the site and characteristics of the rash. A total of 1262 patients seen consecutively in the dermatology department of the Royal Alexandra Hospital for Children, Sydney, Australia, between 1981 and 1995 are described and classified according to the pattern of psoriasis at the time of presentation. Additional information recorded included family history, facial involvement, and history of a psoriatic type of diaper rash in infancy. The ages of the children ranged from 1 month to 15 years. There was an equal gender distribution and a high rate of positive family history at 71%. Twenty-six percent of children had a history of a psoriatic diaper rash and facial involvement occurred in 38% of children. Plaque psoriasis was the most common type overall, affecting 430 patients (34%). Three hundred forty-five children were less than 2 years of age, and this is the largest series of children with psoriasis in this age group presented to date. An entity defined by us as psoriatic diaper rash with dissemination was the most common type of psoriasis in the less than 2-year age group, affecting 155 (45%) patients. This large series offers information on the manifestations of psoriasis in childhood, but is particularly useful in examining the previously less well-described infant age group. The classification used is proposed as a practical way to describe psoriasis in children, particularly with respect to future descriptive studies.

This prospective, single-center, longitudinal cohort study of adult patients with VLS suggests that individualized preventive TCS regimens that achieve objective normality of skin color and texture and are used by compliant patients who attend regular long-term follow-up visits may modify the course of the disease. There was a significant difference in symptom control, scarring, and occurrence of vulvar carcinoma between compliant and partially compliant patients. The adverse effects of TCSs were minimal.

Ichthyosis follicularis with atrichia and photophobia (IFAP syndrome) is a rare X-linked, oculocutaneous human disorder. Here, we assign the IFAP locus to the 5.4 Mb region between DXS989 and DXS8019 on Xp22.11-p22.13 and provide evidence that missense mutations exchanging highly conserved amino acids of membrane-bound transcription factor protease, site 2 (MBTPS2) are associated with this phenotype. MBTPS2, a membrane-embedded zinc metalloprotease, activates signaling proteins involved in sterol control of transcription and ER stress response. Wild-type MBTPS2 was able to complement the protease deficiency in Chinese hamster M19 cells as shown by induction of an SRE-regulated reporter gene in transient transfection experiments and by growth of stably transfected cells in media devoid of cholesterol and lipids. These functions were impaired in five mutations as detected in unrelated patients. The degree of diminished activity correlated with clinical severity as noted in male patients. Our findings indicate that the phenotypic expression of IFAP syndrome is quantitatively related to a reduced function of a key cellular regulatory system affecting cholesterol homeostasis and ability to cope with ER stress.