Qingguo Zhang

Genome-wide association study identifies multiple susceptibility loci for craniofacial microsomia

Craniofacial microsomia (CFM) is a rare congenital anomaly that involves immature derivatives from the first and second pharyngeal arches. The genetic pathogenesis of CFM is still unclear. Here we interrogate 0.9 million genetic variants in 939 CFM cases and 2,012 controls from China. After genotyping of an additional 443 cases and 1,669 controls, we identify 8 significantly associated loci with the most significant SNP rs13089920 (logistic regression P=2.15 × 10−120) and 5 suggestive loci. The above 13 associated loci, harboured by candidates of ROBO1, GATA3, GBX2, FGF3, NRP2, EDNRB, SHROOM3, SEMA7A, PLCD3, KLF12 and EPAS1, are found to be enriched for genes involved in neural crest cell (NCC) development and vasculogenesis. We then perform whole-genome sequencing on 21 samples from the case cohort, and identify several novel loss-of-function mutations within the associated loci. Our results provide new insights into genetic background of craniofacial microsomia.

Modification in the Technique of Ear Framework Fabrication for Congenital Microtia

Background Ear framework fabrication with autologous costal cartilage is considered to be one of the important factors for successful auricular reconstruction. Congenital microtia in adults has many particular physiological characteristics different from that in children. The authors report an effective ear framework–fabricating technique in congenital microtia in adults. Technical points regarding the reduction of the amount of costal cartilage harvested and the increase of the flexibility of the cartilage are discussed. Methods One hundred three adult patients diagnosed with unilateral congenital microtia were treated with skin expansion method for a 2-year period. The ear framework was fabricated using splicing method. The seventh costal cartilage was harvested from 74 patients (with 35 lobular and 39 conchal types) for fabricating the ear framework. For the remaining 29 patients (with 19 lobular and 10 conchal types), both the seventh and eighth cartilages were harvested for fabrication. Result Eighty-four patients (81.55%) were satisfied with the outcome of the reconstructed ear. Fourteen patients (13.60%) found the result acceptable, whereas 5 patients (4.85%) found the result unacceptable. Six patients (5.82%) showed different levels of absorption and cartilage deformation. Five patients (4.85%) were found to have the steel wire extruded. There were no postoperative complications related to chest wall deformity or that affected normal physical function. Ninety-three patients (90.29%) had good recovery of the chest wall. Ten patients (9.71%) had increased chest scar. Conclusions Compared with traditional methods, the technique proposed is a simple approach that can effectively treat adult patients with congenital microtia. This kind of cartilage-harvesting and ear framework–fabricating technique is an appropriate management choice for congenital microtia in adults.

In Vitro Regeneration of Patient-specific Ear-shaped Cartilage and Its First Clinical Application for Auricular Reconstruction

Microtia is a congenital external ear malformation that can seriously influence the psychological and physiological well-being of affected children. The successful regeneration of human ear-shaped cartilage using a tissue engineering approach in a nude mouse represents a promising approach for auricular reconstruction. However, owing to technical issues in cell source, shape control, mechanical strength, biosafety, and long-term stability of the regenerated cartilage, human tissue engineered ear-shaped cartilage is yet to be applied clinically. Using expanded microtia chondrocytes, compound biodegradable scaffold, and in vitro culture technique, we engineered patient-specific ear-shaped cartilage in vitro. Moreover, the cartilage was used for auricle reconstruction of five microtia patients and achieved satisfactory aesthetical outcome with mature cartilage formation during 2.5 years follow-up in the first conducted case. Different surgical procedures were also employed to find the optimal approach for handling tissue engineered grafts. In conclusion, the results represent a significant breakthrough in clinical translation of tissue engineered human ear-shaped cartilage given the established in vitro engineering technique and suitable surgical procedure. This study was registered in Chinese Clinical Trial Registry (ChiCTR-ICN-14005469).

Treatment of Divided Nevus of the Penis with Circumcision and Free Inner Prepuce Grafting.

Summary: Divided nevus of the penis is exceedingly rare. Desruelles et al. reported the first divided nevus on the penis in 1998, and, since then, only 17 cases have been reported in the English language literature. This article presents the successful excision and histopathologic evaluation of the nevi. The glans was reconstructed by a full-thickness skin graft using remnant foreskin. Six months after the operation, the patient showed no deformity of the glans and no loss of sensation. The lesion on the glans can be successfully reconstructed using the remnant foreskin with satisfactory aesthetic and functional outcome. This method is desirable with minimal donor-site morbidity and inconspicuous donor-site scars.

Genome-wide linkage study suggests a susceptibility locus for isolated bilateral microtia on 4p15.32-4p16.2.

Microtia is a congenital deformity where the external ear is underdeveloped. Genetic investigations have identified many susceptibility genes of microtia-related syndromes. However, no causal genes were reported for isolated microtia, the main form of microtia. We conducted a genome-wide linkage analysis on a 5-generation Chinese pedigree with isolated bilateral microtia. We identified a suggestive linkage locus on 4p15.32–4p16.2 with parametric LOD score of 2.70 and nonparametric linkage score (Zmean) of 12.28 (simulated occurrence per genome scan equal to 0.46 and 0.47, respectively). Haplotype reconstruction analysis of the 4p15.32–4p16.2 region further confined the linkage signal to a 10-Mb segment located between rs12505562 and rs12649803 (9.65–30.24 cM; 5.54–15.58 Mb). Various human organ developmental genes reside in this 10-Mb susceptibility region, such as EVC, EVC2, SLC2A9, NKX3-2, and HMX1. The coding regions of three genes, EVC known for cartilage development and NKX3-2, HMX1 involved in microtia, were selected for sequencing with 5 individuals from the pedigree. Of the 38 identified sequence variants, none segregates along with the disease phenotype. Other genes or DNA sequences of the 10-Mb region warrant for further investigation. In conclusion, we report a susceptibility locus of isolated microtia, and this finding will encourage future studies on the genetic basis of ear deformity.

Expansion Method in Secondary Total Ear Reconstruction for Undesirable Reconstructed Ear

BackgroundEar reconstruction by autologous costal cartilage grafting is the most widely applied technique with fewer complications. However, undesirable ear reconstruction brings more problems to plastic surgeons. Some authors resort to free flap or osseointegration technique with prosthetic ear. In this article, we introduce a secondary total ear reconstruction with expanded skin flap method. MethodsFrom July 2010 to April 2012, 7 cases of undesirable ear reconstruction were repaired by tissue expansion method. Procedures including removal of previous cartilage framework, soft tissue expander insertion, and second stage of cartilage framework insertion were performed to each case regarding their local conditions. ResultsThe follow-up time ranged from 6 months to 2.5 years. All of the cases recovered well with good 3-dimensional forms, symmetrical auriculocephalic angle, and stable fixation. ConclusionsAll these evidence showed that this novel expansion method is safe, stable, and less traumatic for secondary total ear reconstruction. With sufficient expanded skin flap and refabricated cartilage framework, lifelike appearance of reconstructed ear could be acquired without causing additional injury.

Occurrence of different external ear deformities in monozygotic twins: report of 2 cases.

Summary: Microtia is a spectrum of congenital deformities, which varies from barely discernable to anotia. Twinning is a well-known risk factor for congenital defects including external ear deformities. Monozygotic twins usually show identical appearances as well as congenital malformations. In special conditions as ear deformities, “mirror-image” may also occur. We report 2 cases of monozygotic twins with different ear deformities. The 8-year-old propositus with lobule type microtia and her identical female twin presented with facial symmetry. Patient A had sausage-type right microtia with absence of external auditory canal. The left external ear showed normal appearance. Patient B presented with left-sided preauricular skin tag and right-sided malformation of tragus with skin tag combined with hyperplasia of underlying cartilage. A granule-size skin tag was also noticed at crus of right helix. A 7-year-old male patient with right-sided conchal type microtia presented to an ear reconstruction center. The patient’s mother showed normal auricular appearance. Her monozygotic twin sister, whose son and daughter had normal ear appearance, was diagnosed with a leftsided lobule type microtia.

Treatment of Folliculitis on the Expanded Postauricular Skin Flap by Topical Iodine Tincture.

1 Zhi-Bin Li, MD Jin-Tian Hu, MD Tun Liu, MD Xu Zhou, MD Qing-Guo Zhang, MD Department of Ear Reconstruction Plastic Surgery Hospital Chinese Academy of Medical Sciences Shi Jing Shan District Beijing, People’s Republic of China Sir: E flap method for microtia reconstruction is widely used in clinical practice, including expanded 1-flap method and expanded 2-flap method.1–3 However, the color, texture, and thickness of the expanded flap can influence the appearance of the reconstructed ear markedly. From September 2007 to January 2015, 1956 patients with microtia or anotia were treated in our department in which 391 patients were treated by expanded one-flap method, while the other 1565 patients were treated by expanded two-flap method. Complications caused by the postauricular tissue expander are common to see, such as hematoma, infection, expander exposure, and expander extravasation. Moreover, folliculitis often appears on the surface of the expanded skin flap (Fig. 1), especially in adolescents and those who have suffered folliculitis on the face. Our department treated 109 patients who had folliculitis with 2% Iodine Tincture since September 2008. We usually paint a radius of 0.6–0.8 cm with tincture of iodine. If the folliculitis has not formed abscess, the erythema would disappear within 1–2 days, or else the abscess gradually vanishes in 3–5 days. A 2% Iodine Tincture is a broad-spectrum, highperformance antiseptic, which can oxidize active genes in a pathogen’s cytoplasmic proteins and interact with amino in proteins, leading to denaturation of the bacteria protein; 2% Iodine Tincture has the ability to kill the vegetative cells and spore rapidly. The bactericidal activity is proportional to the concentration of it. Iodine Tincture is not only active against Gram-positive bacteria, such as Staphylococcus aureus, but also inhibitory for anaerobes and fungi. When local abscess forms in folliculitis patients, it is mainly treated by incision and drainage or rupturing the surface of the abscess.4 While the expanded skin flaps are generally thin, inappropriate procedure may result in the expander exposure. Owing to the expanded skin flap lying over the costal cartilages framework with no blood supply, local breakdown of the flap may lead to cartilage exposure. Twenty samples were collected when the folliculitis formed abscess. The positive rate of bacteria culture was 20% (4/20), 6 pathogenic bacteria were cultivated, 4 of 6 Gram-positive bacteria (67%) were S. aureus. The effect of using Iodine Tincture locally is direct and reliable. When we painted folliculitis with Iodine Tincture, trace amounts of ethanol volatilize immediately, iodide ion deposit and osmosis to stroma layer. With 2% Iodine Tincture, the hyphae were damaged rapidly, the lesion contracted gradually, necrosis of tissue was broken off, and collagen fibers were repaired to

Microtia Combined With Split Sole of Feet, Deformed Middle Fingers and Café -au-lait Spots on the Trunk: A New Association.

AbstractMicrotia is a spectrum of congenital deformities. Approximately, half of the patients are associated with hemifacial microtia. The birth rate of microtia ranges from 2 per 10,000 to 17.4 per 10,000.1 Microtia and limb deformities sometimes occurred simultaneously as described in the literature. In this report, the patient was found to be with unilateral microtia combined with bilateral split sole of feet, deformed middle fingers on both hands, and café-au-lait spots on the trunk. Despite a thorough literature search, the authors could not achieve a satisfactory diagnosis for the current case with respect to the type of anomalies seen in the case.

The Retrograde Transposition of the Remnant Earlobe in Patients With Low-Set Microtia.

AbstractDuring auricle reconstruction, lobular transposition has become a routine technique applied by most of surgeons. But to some low-set remnant ears, it is difficult to manipulate the conventional lobule transposition method in clinical application. In this article, the authors introduce a method to retrogradely transpose the remnant ear with the the ratio of length:width of the lobular flap being 4–5:1. The lobule transposition could be applied during the first stage of Nagata method or the third stage using expansion method. The authors take the superior part of the remnant ear as the pedicle and make the incision at the middle and inferior parts of the remnant ear to form the lobular flap. Then the inferior lobule is rotated posteriorly and superiorly to cover the rear end of the framework and to form the inferior part of helical rim. The results of the reconstructed auricles are satisfactory with aesthetic natural earlobes and the location of the reconstructed ear is symmetric to the contralateral ear. The authors believe that to the 2% to 5% patients with low-set microtia, this is a good way to make use of remnant ear for the purpose of a real earlobe.