Congenital fibrosis of extraocular muscles (CFEOM) syndrome is a genetically determined congenital disorder characterized by non-progressive ophthalmoplegia, restrictive ocular fixation, and ptosis. Its estimated incidence is approximately 1 in 230 000 to 250 000. This paper reports a family with type 3 CFEOM diagnosed at the Second Xiangya Hospital of Central South University. The proband was a 10-year-old female who presented with right esotropia and right upper eyelid ptosis. Whole-exome sequencing revealed a heterozygous c.904G>A mutation in the TUBB3 gene. Genetic testing of family members identified that the proband's mother carried the same mutation and exhibited left eyelid ptosis. The child underwent strabismus correction followed by ptosis repair, both of which led to marked postoperative improvement. For children presenting with congenital extraocular movement restriction and ptosis, genetic testing plays a crucial role in confirming the diagnosis and guiding family analysis. Additionally, individualized surgical intervention can significantly improve both ocular function and cosmetic appearance.
Humans ; Female ; Child ; Ophthalmoplegia/congenital* ; Fibrosis/congenital* ; Blepharoptosis/surgery* ; Mutation ; Tubulin/genetics* ; Pedigree ; Male ; Esotropia/genetics* ; Congenital Cranial Dysinnervation Disorders

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a patient with Weiss-Kruszka syndrome (WSKA). METHODS: A male patient presented with primary infertility for 1 year post-marriage, intellectual disability, and blepharoptosis at Huzhou Maternity and Child Health Care Hospital from October to December 2024 was selected as the study subject. Peripheral blood samples were collected from the patient and his family members. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Ethics Committee of the Hospital (Ethics No. 2023-R-010). RESULTS: The patient, a 29-year-old male, had exhibited short stature, trigonocephaly, bilateral blepharoptosis, arched eyebrows, brachydactyly, redundant skin folds, webbed neck, hypertrichosis, mild intellectual disability, and speech impairment. WES revealed that he has harbored a de novo heterozygous frameshifting variant of the ZNF462 gene, namely c.945_946del (p.T316Rfs*42). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PM2_Supporting+PVS1+PM6_Supporting). CONCLUSION The ZNF462 c.945_946del variant probably underlay the WSKA in this patient. Above finding has enriched the mutational spectrum of the ZNF462 gene.
Humans ; Male ; Adult ; Intellectual Disability/genetics* ; Transcription Factors/genetics* ; Exome Sequencing ; Mutation ; Abnormalities, Multiple/genetics* ; Blepharoptosis/genetics*

OBJECTIVE: To analyze the genotype and clinical phenotype of a 3-month-old female infant featuring unresponsiveness. METHODS: The infant was subjected to genetic testing, and her clinical features were compared with syndromes associated with variants of the candidate gene. RESULTS: The patient has featured long fingers, long and overlapped toes, musk-like face, blepharophimosis, ptosis, and lacrimal duct anomaly. She was found to harbor a heterozygous de novo variant NM_012330.3: c.3040C>T (p.Gln1014*) in exon 16 of the KAT6B gene. Her clinical phenotype and genotype have both conformed to Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS). CONCLUSION The child was diagnosed with SBBYSS syndrome due to the c.3040C>T (p.Gln1014*) variant of the the KAT6B gene. Discovery of the unique features has expanded the phenotypic spectrum of this syndrome.
Female ; Humans ; Blepharophimosis/genetics* ; Blepharoptosis ; Genotype ; Histone Acetyltransferases ; Infant

BACKGROUNDBlepharophimosis ptosis epicanthus inversus syndrome (BPES) is a rare congenital ophthalmic disorder, characterized by congenital eyelid malformation including bilateral ptosis, shortening of the horizontal eyelid fissure, epicanthus inversus, and increased distance between the inner canthi. In this research, we studied the histological structure and ultrastructure of medial canthal ligament of patients with BPES.

METHODSThirty patients with BPES who received plastic surgery at the Zhongshan Ophthalmic Center from March 2006 to January 2008 were studied. There were 17 males and 13 females with an average age of (8.73 +/- 3.37) years (3 - 31 years). The medial canthal ligaments of patients were collected during the plastic surgery to analyze the histological structure by hematoxylin and eosin (HE), Congo red, van Gieson's (VG), Masson trichrome and aldehyde-fuchsin staining. The ultrastructures of the medial canthal ligaments were also analyzed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Fifteen samples of medial canthal ligament from healthy persons with an average age of (9.02 +/- 3.12) years (6 - 30 years) were collected as a control group.

RESULTSMorphological and histological study showed that the medial canthal ligaments of BPES patients were composed of collagen fibers, a few elastic fibers and striated muscles. The collagen fibers assemblies were disorganized and the fibrous connective tissues were undergoing hyaline degeneration. The karyopycnosis of fibroblasts was located among the collagen fibrils and the numbers of fibroblasts were decreased. Ultrastructural study with SEM showed that the collagen fibers were larger than normal, irregular and loose. Parts of the collagen fibers were broken and had a coarse surface. Ultrastructural study with TEM showed that the fibroblasts had less cytoplasm, fewer organelles and the nucleus displayed pyknosis.

CONCLUSIONSThe medial canthal ligament in BPES patients is composed chiefly of collagen fibers. The collagen fibers of medial canthal ligaments in BPES patients are disorganized and hyaline degeneration is present. The study revealed that the medial canthal ligament of BPES patients might have congenital dysplasia.

Adolescent ; Adult ; Blepharophimosis ; genetics ; pathology ; Blepharoptosis ; genetics ; pathology ; Child ; Child, Preschool ; Eyelids ; abnormalities ; pathology ; ultrastructure ; Female ; Humans ; Male ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Syndrome

Abnormalities, Multiple ; genetics ; Amino Acid Sequence ; Blepharophimosis ; genetics ; Blepharoptosis ; genetics ; Eyelids ; abnormalities ; Female ; Forkhead Box Protein L2 ; Forkhead Transcription Factors ; genetics ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Syndrome

OBJECTIVETo screen mutations in the forkhead transcriptional factor 2 gene (FOXL2) in six Chinese families with blepharophimosis, ptosis, and epicanthus inversus syndrome(BPES).

METHODSPCR amplification and direct sequencing of the FOXL2 coding region in genomic DNA were performed in affected patients and 80 healthy controls. BLAST analysis of the sequence was made on Internet.

RESULTSA novel 951-953(delC) was found in the two affected patients of a Chinese family with BPES. No mutations were found in the healthy controls. The 951-953(delC) may cause a frameshift mutation after codon 238 that exists downstream of the forkhead domain, resulting in the production of truncated proteins.

CONCLUSIONThese findings indicated that the 951-953(delC) deletion mutation in the two patients resulted in truncated proteins and hence led to their BPES. To the authors' knowledge, the 951-953(delC) in FOXL2 has not been previously reported.

Amino Acid Sequence ; Base Sequence ; Blepharophimosis ; genetics ; Blepharoptosis ; genetics ; China ; Eyelid Diseases ; genetics ; Family Health ; Female ; Forkhead Box Protein L2 ; Forkhead Transcription Factors ; genetics ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Pedigree ; Sequence Alignment