Angioma serpiginosum with oesophageal papillomatosis is an X-linked dominant condition that maps to Xp11.3–Xq12

Abstract

We report on a four-generation family with localized subepidermal telangiectasias following Blaschko's lines (angioma serpiginosum). The vascular streaks are present at birth and progress slowly thereafter. In several family members papillomatosis of the entire oesophagus was found to be part of the condition. Mild nail and hair dystrophy added to the resemblance of Goltz -Gorlin syndrome (focal dermal hypoplasia), suggesting that the present condition could be a mild variant. All affected family members are females, there is no increased miscarriage rate, and X-inactivation in affected females is highly skewed, compatible with X-linked dominant inheritance with very early in utero lethality in males. In the family, 11 informative meioses were available to study the segregation of X-chromosome markers. Significant linkage (LOD score 3.31) was found to a region flanked by markers DXS8026 and DXS106 (44 -67 Mb from Xpter) that includes the centromere.

Goltz–Gorlin (focal dermal hypoplasia) and the microphthalmia with linear skin defects (MLS) syndrome: no evidence of genetic overlap

“…11,12 A 112-kb deletion including PORCN was found in four female patients from a three-generation family with localized subepidermal telangiectasias following Blaschko's lines (angioma serpiginosum), a rare skin disorder that has been suggested to be allelic to FDH. 20,22 Taken together, female patients with an intragenic PORCN mutation and random XCI are supposed to show the classical FDH phenotype. In these cases, somatic mosaicism can lead to a milder phenotype.…”

An Xp11.23 deletion containing PORCN may also cause angioma serpiginosum, a cosmetic skin disease associated with extreme skewing of X-inactivation

“…1 The presence of very mild nail dystrophy, with affection of no more than 1 -4 nails per patient, and concomitant nonsymptomatic oesophageal papillomatosis, led to the suggestion that angioma serpiginosum might be allelic to focal dermal hypoplasia (FDH). 1 The affected females' only complaint was cosmetic due to the emergence of vascular streaks along Blaschko's lines. The rash progressed from childhood to adulthood.…”

Genetics of Hemangiomas, Vascular Malformations, and Primary Lymphedema

“…Table 2 lists an additional 10 loci, abnormalities of which have been reported in patients with vascular anomalies but for which specific genes have not yet been identified. 22,[31][32][33][34][35][36][37][38][39] Taken together, 36 series and/or kindreds support an association between a chromosomal region and Z1 vascular anomalies. Three genetic abnormalities were each reported in only single cases, hence those associations are weak.…”