OBJECTIVE: To explore the prenatal and postnatal features and genetic characteristics of patients with Lymphedema-Distichiasis syndrome (LDS) due to variants of FOXC2 gene. METHODS: A retrospective analysis was carried out on the phenotypic information, fetal ultrasound image, and genetic testing of two Chinese pedigrees diagnosed at the Third Affiliated Hospital of Zhengzhou University. A literature review was also carried out by searching the China National Knowledge Infrastructure (CNKI), Wanfang Database, and PubMed databases dated from January 2010 to June 2024 using keywords "Lymphedema-Distichiasis syndrome " and "FOXC2 ". This study has been approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethic No. 2021-046-01). RESULTS: Neither family was found to harbor chromosomal aneuploidy or pathogenic CNVs larger than 100 kb. The fetuses from pedigree 1 and pedigree 2 were respectively found to be heterozygous for a c.361C>T (p.R121C) variant and a c.168C>A (p.Y56*) variant of the FOXC2 gene. Both variants were paternally derived. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were classified as pathogenic and likely pathogenic, respectively. Literature search has identified 20 articles, and combined with our cases, a total of 117 patients were identified. Among them, 13 had shown prenatal phenotypes, primarily with increased nuchal translucency (NT) (12/13), urinary abnormalities (5/12), and fetal edema (4/13). Postnatal phenotypes were observed in 110 cases, mainly as distichiasis (87/110) and lymphedema (73/110). Only 6 cases had both prenatal and postnatal phenotypes. A total of 32 genetic variants were identified. CONCLUSION The primary prenatal manifestations of LDS include increased NT, fetal edema, pleural and abdominal effusion, and separation of renal collecting system. Postnatal phenotypes are primarily characterized by lymphedema, distichiasis, and spinal extradural arachnoid cysts. Discovery of the c.168C>A variant has expanded the spectrum of FOXC2 gene mutations in China.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; East Asian People/genetics* ; Eyelashes/abnormalities* ; Forkhead Transcription Factors/genetics* ; Genetic Testing ; Lymphedema/genetics* ; Pedigree ; Phenotype ; Retrospective Studies

OBJECTIVE: To analyze FOXC2 gene variant in a family affected with lymphodema-distichiasis syndrome (LDS). METHODS: Peripheral blood samples were collected for the extraction of DNA and protein. Whole-exome sequencing was carried out to detect variants in the proband. Suspected variant was validated by Sanger sequencing. Western blotting was used to detect changes in protein expression. RESULTS: The proband and his mother were both found to carry a heterozygous nonsense variant c.177C>G (p.Tyr59X) of the FOXC2 gene, which was previously unreported. Down-regulated expression of FOXC2 was detected by Western blotting. Prenatal ultrasonography of the fetus indicated increased nuchal thickness. Amniocentesis was performed at 21+1 weeks of pregnancy, genetic testing suggested that the fetus also carried the c.177C>G variant. CONCLUSION The patients' condition may be attributed to the heterozygous nonsense variant c.177C>G of the FOXC2 gene, which resulted in a significant decrease in FOXC2 expression. Increased nuchal thickness may also be related with decreased FOXC2 expression. Above finding has expanded the variant spectrum of the FOXC2 gene.
Codon, Nonsense ; Eyelashes ; abnormalities ; Female ; Forkhead Transcription Factors ; genetics ; metabolism ; Gene Expression ; Genetic Testing ; Genetic Variation ; Humans ; Lymphedema ; genetics ; Pedigree ; Pregnancy ; Prenatal Diagnosis

PURPOSE: Traumatic telecanthus can result from naso-ethmoid-orbital fractures. Repair of the medial canthal tendon(MCT) using transnasal wiring is regarded as a choice of method to treat telecanthus, however, is often complicated by incomplete anchoring and drift of canthus, extrusion of wire, in-fracture of orbital bone, and eye damage. The authors introduced oblique transnasal wiring method through the Hiraga's epicanthopalsty incision instead of well-known classical bicoronal approach. METHODS: Five patients with traumatic telecanthus were treated with this method. Though the Hiraga's epicanthoplasty incision, we could approach the operative field; the medial orbital wall and detached MCT. Oblique transnasal wiring was performed as following steps. After slit skin incision on the contralateral nasal recession area, drill holes were made from this point to the superior and posterior point of lacrimal sac of deformed eye. A 2-0 wire was double-passed through the holes and MCT. Traction was applied to ensure pulling the MCT and the wires were twisted in the contralateral nose, securing the MCT in the correct position. RESULTS: All patients except 1 person showed improvement and rapid recovery. On average each canthus was moved 5.6mm medially. In all cases, there were no eyelashes disappear, lacrimal canaliculitis, lacrimal duct injury, or infections. CONCLUSION: The Hiraga's epicanthoplasty incision could give sufficient operative field to reattach the MCT in traumatic telecanthus patients. And the oblique transnasal wiring technique is effective for the Asians who have flat nose and exophthalmic eye. The authors conclude that this technique could be a simple, safe and scarless method to correct traumatic telecanthus.
Asian Continental Ancestry Group ; Corneal Ulcer ; Craniofacial Abnormalities ; Dacryocystitis ; Dietary Sucrose ; Eye ; Eyelashes ; Humans ; Mandrillus ; Nose ; Orbit ; Skin ; Traction ; Canaliculitis

PURPOSE: To evaluate the effect of epiblepharon surgery on visual acuity and with-the-rule astigmatism in children compared to patients without surgical treatment. METHODS: We undertook a retrospective case control study and reviewed the charts of 202 eyes treated with epiblepharon surgery and of 142 eyes without surgery. The surgical procedure for epiblepharon correction used rotating suture techniques. Data regarding age, best corrected visual acuity, and degree of astigmatism were recorded. Baseline and 1-, 3-, 6-, and 12-month postoperative data were collected. The chi-square test, Student's t-test and general linear model analysis for repeated measures were applied. RESULTS: The mean astigmatism in the surgical group decreased from 1.10 +/- 1.02 diopter (D) preoperatively to 0.84 +/- 1.05 D at 3 months after surgery (p < 0.05). However, there was no statistically significant difference compared to the non-surgical group during the first year. The general linear model analysis comparing the mean astigmatism between the two groups over time showed a significant group-time interaction (p < 0.05). Within the surgical group, the higher baseline astigmatic subgroup and the 5- to 8-year-old group demonstrated greater cylinder reduction over time. The change in mean visual acuity was not significant in either group. CONCLUSIONS: Significant astigmatic reduction was found after surgical correction in epiblepharon patients. Patients with higher baseline astigmatism exhibited greater astigmatic reduction after epiblepharon surgery. These results suggest that, in order to reduce astigmatism, an epiblepharon operation should be considered in patients with a high level of astigmatism.
Astigmatism/*etiology/*physiopathology ; Case-Control Studies ; Child ; Child, Preschool ; Eye Abnormalities/*complications/*surgery ; Eyelashes/pathology ; Eyelids/*abnormalities/pathology/surgery ; Female ; Humans ; Male ; Retrospective Studies ; Treatment Outcome ; *Visual Acuity

We report a sporadic case of hypotrichosis simplex of the scalp, a rare genotrichosis, characterized by sparse or absent scalp hair with no structural defect of the hair shaft, in the absence of other ectodermal or systemic abnormalities. A 9-year-old girl had normal-looking hair at birth but subsequently lost the hair on her scalp after she turned 3 years of age. However, her eyebrows and eyelashes remained normal. Skin, nails and teeth were also normal except for malocclusion. No other family member had a similar hair defect. Hair shaft examination did not reveal any structural abnormalities. Microscopic examination of a scalp biopsy specimen showed a reduced number of hair follicles.
Biopsy ; Child ; Congenital, Hereditary, and Neonatal Diseases and Abnormalities ; Ectoderm ; Eyebrows ; Eyelashes ; Female ; Hair ; Hair Follicle ; Humans ; Hypotrichosis* ; Malocclusion ; Parturition ; Scalp* ; Skin ; Tooth