CHST14/D4ST1 deficiency: New form of Ehlers–Danlos syndrome

Carbohydrate sulfotransferase 14/dermatan 4‐O‐sulfotransferase‐1 (CHST14/D4ST1) deficiency represents a specific form of Ehlers–Danlos syndrome (EDS) caused by recessive loss‐of‐function mutations in CHST14. The disorder has been independently termed “adducted thumb–clubfoot syndrome”, “EDS, Kosho type”, and “EDS, musculocontractural type”. To date, 31 affected patients from 21 families have been described. Clinically, CHST14/D4ST1 deficiency is characterized by multiple congenital malformations (craniofacial features including large fontanelle, hypertelorism, short and downslanting palpebral fissures, blue sclerae, short nose with hypoplastic columella, low‐set and rotated ears, high palate, long philtrum, thin upper lip vermilion, small mouth, and micro‐retrognathia; multiple congenital contractures including adduction–flexion contractures and talipes equinovarus as well as other visceral or ophthalmological malformations) and progressive multisystem fragility‐related complications (skin hyperextensibility, bruisability, and fragility with atrophic scars; recurrent dislocations; progressive talipes or spinal deformities; pneumothorax or pneumohemothorax; large subcutaneous hematomas; and diverticular perforation). Etiologically, multisystem fragility is presumably caused by impaired assembly of collagen fibrils resulting from loss of dermatan sulfate (DS) in the decorin glycosaminoglycan side chain that promotes electrostatic binding between collagen fibrils. This is the first reported human disorder that specifically affects biosynthesis of DS. Its clinical characteristics indicate that CHST14/D4ST1 and, more fundamentally, DS, play a critical role in fetal development and maintenance of connective tissues in multiple organs. Considering that patients with CHST14/D4ST1 deficiency develop progressive multisystem fragility‐related manifestations, establishment of a comprehensive and detailed natural history and health‐care guidelines as well as further elucidation of the pathophysiology in view of future etiology‐based therapy are crucial.     

A Say‐Barber‐Biesecker‐Young‐Simpson variant of Ohdo syndrome with a KAT6B 10‐base pair palindromic duplication: A recurrent mutation causing a severe phenotype mixed with genitopatellar syndrome

The Say‐Barber‐Biesecker‐Young‐Simpson variant of Ohdo syndrome (SBBYSS) (MIM# 603736) and genitopatellar syndrome (GPS) (MIM#606170) are allelic diseases caused by KAT6B mutation. Genotype–phenotype correlation is assumed, but a few patients manifest overlapping features of both syndromes. Here we report the case of a boy with SBBYSS. He had a KAT6B mutation previously reported in typical SBBYSS, but he also manifested severe developmental delay, as well as genital features and laryngomalacia requiring tracheostomy that conformed to GPS.     

Twin–twin transfusion syndrome,coarctation of the aorta and hypoplastic aortic arch: A case series report

Aim: The twin–twin transfusion syndrome (TTTS) complicates 10–30% of monochorionic pregnancies. The incidence of pulmonary stenosis and endocardial fibroelastosis is especially high in the recipient twin. We report a novel finding of four cases of coarctation of the aorta and hypoplastic aortic arch in the donor to raise awareness of cardiac lesions in twins affected by TTTS. Method: Retrospective review of both neonatal database and mortality data from 2002 to 2007 with cross‐validation from the local tertiary cardiology unit data (1998–2006) to identify children presenting with coarctation who were also twins. Results: We identified four monochorionic twin pairs affected by the TTTS, delivered between 25 weeks and 36 weeks' gestation, where the donor was found to have coarctation of the aorta or a hypoplastic aortic arch. In addition, two of the four recipients also had cardiac abnormalities. There was a high mortality rate of 30% for both twins, and a high morbidity rate, especially for neurological sequelae. Conclusion: We believe that the types of abnormalities seen may be explained by the altered fetal blood flow and haemodynamics in TTTS. Given the increased prevalence of congenital heart disease in TTTS, with an increased risk of coarctation in the donor twin and pulmonary stenosis in the recipient, intra‐uterine surveillance and a post‐natal comprehensive cardiac assessment for both twins is warranted.