Short anagen hair syndrome: association with mono- and biallelic variants in WNT10A and a genetic overlap with male pattern hair loss.

BACKGROUND: Short anagen hair (SAH) is a rare paediatric hair disorder characterized by a short anagen phase, an inability to grow long scalp hair and a negative psychological impact. The genetic basis of SAH is currently unknown. OBJECTIVES: To perform molecular genetic investigations in 48 individuals with a clinical phenotype suggestive of SAH to identify, if any, the genetic basis of this condition. METHODS: Exome sequencing was performed in 27 patients diagnosed with SAH or with a complaint of short, nongrowing hair. The cohort was screened for variants with a minor allele frequency (MAF) < 5% in the general population and a Combined Annotation Dependent Depletion (CADD) score > 15, to identify genes whose variants were enriched in this cohort. Sanger sequencing was used for variant validation and screening of 21 additional individuals with the same clinical diagnosis and their relatives. Genetic association testing of SAH-related variants for male pattern hair loss (MPHL) was performed using UK Biobank data. RESULTS: Analyses revealed that 20 individuals (42%) carried mono- or biallelic pathogenic variants in WNT10A. Rare WNT10A variants are associated with a phenotypic spectrum ranging from no clinical signs to severe ectodermal dysplasia. A significant association was found between WNT10A and SAH, and this was mostly observed in individuals with light-coloured hair and regression of the frontoparietal hairline. Notably, the most frequent variant in the cohort [c.682T>A;p.(Phe228Ile)] was in linkage disequilibrium with four common WNT10A variants, all of which have a known association with MPHL. Using UK Biobank data, our analyses showed that c.682T>A;p.(Phe228Ile) and one other variant identified in the SAH cohort are also associated with MPHL, and partially explain the known associations between WNT10A and MPHL. CONCLUSIONS: Our results suggest that WNT10A is associated with SAH and that SAH has a genetic overlap with the common phenotype MPHL. The presumed shared biologic effect of WNT10A variants in SAH and MPHL is a shortening of the anagen phase. Other factors, such as modifier genes and sex, may also play a role in the clinical manifestation of hair phenotypes associated with the WNT10A locus.

The vascularized groin lymph node flap (VGLN): Anatomical study and flap planning using multi-detector CT scanner. The golden triangle for flap harvesting.

INTRODUCTION: A growing number of surgeons perform lymph node transfers for the treatment of lymphedema. When harvesting a vascularized lymph node groin flap (VGLNF) one of the major concerns is the potential risk of iatrogenic lymphedema of the donor-site. This article helps understanding of the lymph node distribution of the groin in order to minimize this risk. MATERIALS AND METHODS: Fifty consecutive patients undergoing abdominal mapping by multi-detector CT scanner were included and 100 groins analyzed. The groin was divided in three zones (of which zone II is the safe zone) and lymph nodes were counted and mapped with their distances to anatomic landmarks. Further node units were plotted and counted. RESULTS: The average age was 48 years. A mean number of nodes of 6.5/groin was found. In zone II, which is our zone of interest a mean of 3.1 nodes were counted with a mean size of 7.8 mm. In three patients no nodes were found in zone II. In five patients nodes were seen in zone II but were not sufficient in size or number to be considered a lymph node unit. On average the lymph node unit in zone II was found to be 48.3 mm from the pubic tubercle when projected on a line from the pubic tubercle to the anterior superior iliac spine, 16.0 mm caudal to this line, and 20.4 mm above the groin crease. On average the lymph node unit was a mean of 41.7 mm lateral to the SCIV-SIEV confluence. CONCLUSION: This study provides increased understanding of the lymphatic anatomy in zone II of the groin flap and suggests a refined technique for designing the VGLNF. As with any flap there is a degree of individual patient variability. However, having information on the most common anatomy and flap design is of great value.