Ectodermal dysplasia is a group of hereditary diseases characterized by developmental defects of ectodermal structures. Its oral manifestations mainly center on congenital missing teeth, abnormal tooth morphology, and maxillofacial bone developmental disorders, which seriously affect the masticatory function, maxillofacial development, and mental health of affected children. In this article, the multidimensional diagnostic strategy system for children with ectodermal dysplasia and the related progress of early oral prosthodontic treatment methods were systematically reviewed to provide references for clinicians in the diagnosis and treatment of children with ectodermal dysplasia.
Child ; Humans ; Anodontia ; Ectodermal Dysplasia/diagnosis* ; Prosthodontics ; Tooth Abnormalities/therapy*

This article reports a child with cardioaciocutaneous syndrome (CFCS) caused by a rare microdeletion of chromosome 19p13.3, and a literature review is conducted. The child had unusual facies, short stature, delayed mental and motor development, macrocephaly, and cardiac abnormalities. Whole-exome sequencing identified a 1 040 kb heterozygous deletion in the 19p13.3 region of the child, which was rated as a "pathogenic variant". This is the first case of CFCS caused by a loss-of-function mutation reported in China, which enriches the genotype characteristics of CFCS. It is imperative to enhance the understanding of CFCS in children. Early identification based on its clinical manifestations should be pursued, and genetic testing should be performed to facilitate diagnosis.
Humans ; Chromosome Deletion ; Chromosomes, Human, Pair 19/genetics* ; Ectodermal Dysplasia/genetics* ; Facies ; Failure to Thrive/genetics* ; Heart Defects, Congenital/genetics*

OBJECTIVE: To investigate the clinical characteristics and genetic etiology of eight members from a pedigree affected with epidermolysis bullosa (EB). METHODS: A girl presented with recurrent, unexplained blisters on the palmar and plantar skin for 8 years and sought medical care in October 2024 was enrolled as the study subject. A retrospective study was conducted to collect the child's clinical data, and a detailed medical history was taken for her family members. Peripheral venous blood samples were collected from the child and her parents for genomic DNA extraction. Whole-exome sequencing (WES) was performed. Candidate variant was validated by Sanger sequencing. The pathogenicity of the candidate variants was classified in accordance with the Standards and Guidelines for the Interpretation of Sequence Variants issued by the American College of Medical Genetics and Genomics (ACMG, hereinafter referred to as the "ACMG Guidelines"). This study was approved by the Medical Ethics Committee of the 980th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army (Ethics No.: 2019-KY-01). RESULTS: The proband was an 8-year-and-4-month-old female. Four months after birth, she had developed recurrent blisters on the palmar and plantar skin without obvious triggers, accompanied by significant pain. Symptoms were more severe in summer and slightly relieved in winter. Although symptomatic treatment could alleviate the symptoms, she was unable to participate in physical activities. A detailed family history revealed that her great-grandfather, grandfather, father, half-brother, great-aunt, great-aunt's son and two grandsons, as well as her aunt and aunt's son, had similar clinical manifestations. WES revealed that she has harbored a heterozygous c.556-16(IVS1)C>G (NM_000424.4) variant in the KRT5 gene, which was identified as a splice site mutation. Reverse transcription sequencing confirmed that this variant can disrupt normal splicing, resulting in retention of a 15 bp sequence in the first intron. Sanger sequencing demonstrated that the variant was inherited from the father, and the 6 aforementioned relatives with similar phenotypes have all carried the same variant (the great-grandfather, grandfather, and great-aunt had declined genetic testing due to advanced age). Based on the ACMG guidelines, this variant was classified as pathogenic (PS3+PM2_Supporting+PP3+PP1_strong). CONCLUSION Patients with epidermolysis bullosa simplex may exhibit clinical features including blistering on the skin or mucous membranes of friction-prone sites (e.g. hands, feet, elbows, and knees) following minor trauma or friction, as well as increased skin fragility. The c.556-16(IVS1)C>G (rs376462752) variant of the KRT5 gene probably underlay the pathogenesis of EB in this child. Above findings have enriched the mutational spectrum of the KRT5 gene.
Child ; Female ; Humans ; Infant ; Male ; China ; Epidermolysis Bullosa Simplex/genetics* ; Exome Sequencing ; Keratin-5/genetics* ; Mutation ; Pedigree ; Retrospective Studies ; East Asian People/genetics*

OBJECTIVE: To explore the clinical and genetic characteristics of five fetuses with Harlequin ichthyosis (HI). METHODS: Five fetuses with HI diagnosed at Guangdong Women and Children Hospital between 2017 and 2024 were selected as study subjects. Clinical and laboratory data were collected and reviewed. Whole exome sequencing (WES) was carried out, and candidate variants were verified by bioinformatic analysis. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 202401024). RESULTS: The five fetuses had presented with ectropion, eclabium and contracture and flexion of fingers and toes. WES revealed that all had harbored compound heterozygous or homozygous variants of the ABCA12 gene. Among the eight types of variants, five were unreported previously. CONCLUSION The compound heterozygous or homozygous variants of the ABCA12 gene probably underlay the HI in the five fetuses. Clinicians should be vigilant about the possibility of HI in fetus with ectropion, eclabium, and contracture and flexion of fingers and toes.
Humans ; Ichthyosis, Lamellar/genetics* ; Female ; ATP-Binding Cassette Transporters/genetics* ; Pregnancy ; Genotype ; Phenotype ; Exome Sequencing ; Fetus ; Mutation ; Male ; Adult

OBJECTIVE: To explore the clinical phenotype and genetic etiology of a child with Ehlers-Danlos syndrome, spondylodysplastic type 2 (EDSSPD2). METHODS: A child who was admitted to the Children's Medical Center of the Affiliated Hospital of Guangdong Medical University in July 2024 for "delayed motor development for 1 and a half year" was selected as the study subject. Clinical data of the child was collected, including medical history, family history, and results of auxiliary examinations. Peripheral venous blood samples were collected from the child and his two brothers and both parents. Genomic DNA was extracted from the child and his family members and subjected to whole-exome sequencing (WES) and copy number variation (CNV) analysis. Sanger sequencing was used to verify the parental origin of the candidate variants. Multiple protein function prediction software tools, including SIFT, PolyPhen-2, and REVEL, were used to assess the impact of candidate variants on the protein function. Based on protein database information from UniProt, a two dimensional structural schematic of the target protein was generated. The pathogenicity of the variants was classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Relevant literature on the B3GALT6 gene variants leading to EDSSPD2 was retrieved from CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases. The procedures followed in this study were reviewed and approved by the Medical Ethics Committee of Affiliated Hospital of Guangdong Medical University (Ethics No.：PJ2021-097). RESULTS: The proband was a 2-year-old male with an onset in infancy. The main clinical manifestations included loose skin, scoliosis and kyphosis, generalized hypermobility of joints, and motor developmental delay. WES has revealed two compound heterozygous variants of the B3GALT6 gene (NM_080605.4): c.766C>T (p.Arg256Trp) and c.962G>A (p.Cys321Tyr). Sanger sequencing verification showed that the c.766C>T and c.962G>A variants were respectively derived from his phenotypically normal father and mother. Bioinformatics analysis showed that for the c.766C>T (p.Arg256Trp) variant, the Arg256 site is located within the galactosyltransferase catalytic domain (GalT domain) of the β3GalT6 protein. According to the ACMG guidelines, the c.766C>T variant was classified as a likely pathogenic (PS3+PM2_supporting+PM3+PP3), and the c.962G>A was classified as a variant of unknown significance (PM2_Supporting+PM3+PP3). By following the pre-set literature retrieval strategy, a total of 12 articles related to B3GALT6 gene variants were identified (11 English and 1 Chinese), which involved a total of 71 patients. Among these, 4 reports (involving 20 patients) involved B3GALT6 gene variants leading to EDSSPD2. Among the 18 live-born EDSSPD2 patients (including the proband in this study), common clinical manifestations have included scoliosis (88.9%, 16/18), generalized hypotonia (83.3%, 15/18), and soft and lax skin (66.7%, 12/18). Some patients already showed skeletal abnormalities on prenatal ultrasound scan (22.2%, 4/18), while a few presented with cervical instability (16.7%, 3/18). One child had deceased at 18 months of age due to hypoxia caused by tracheomalacia and tracheal compression due to scoliosis. Among the 23 reported EDSSPD2 related B3GALT6 variant sites, missense variants were the most common (78.3%, 18/23), followed by nonsense variants (21.7%, 5/23). CONCLUSION Above finding has enriched the clinical and mutational spectra of EDSSPD2. Early genetic testing has important clinical value for the diagnosis, differential diagnosis, and genetic counseling of this disease.
Humans ; Male ; Ehlers-Danlos Syndrome/genetics* ; Pedigree ; N-Acetylgalactosaminyltransferases/genetics* ; Asian People/genetics* ; DNA Copy Number Variations ; Exome Sequencing ; Female ; Child ; Child, Preschool ; Phenotype ; Mutation ; China ; East Asian People ; Galactosyltransferases

OBJECTIVES

To present a rare case of a 17-year-old girl with multiple odontogenic keratocysts, skeletal abnormalities, central nervous system and cutaneous anomalies.

METHODS

Design:Case Report

Setting:Tertiary Government Training Hospital

Patient: One

RESULTS

A 17-year-old Filipino girl presented with a one-year history of progressive left mandibular swelling. Orthopantomography revealed multiple cysts involving the mandible and maxillae. Histopathologic examination of incision biopsy specimens confirmed odontogenic keratocysts. Other physical examination findings included coarse face and multiple palmar and plantar pits. Radiologic investigations demonstrated calcification of the falx cerebri and tentorium cerebelli, bifid rib and cervicothoracic scoliosis. Based on clinical, radiological, and histopathological findings, a diagnosis of Gorlin-Goltz syndrome was established. The patient underwent enucleation and curettage of the cysts with peripheral ostectomy, and there was no recurrence on repeat orthopantomography at six months and two years post-operatively. However, on the fourth year, the patient claimed there was a mandibular cyst which was not verified as she was lost to follow-up.

CONCLUSION

This case highlights the importance of recognizing multiple odontogenic keratocysts as a potential manifestation of Gorlin-Goltz Syndrome. Early diagnosis enables appropriate management and long term surveillance to monitor for other manifestations of this syndrome that may occur later in life.

Human ; Female ; Adolescent: 13-18 Yrs Old ; Basal Cell Nevus Syndrome ; Mandible ; Radiography, Panoramic ; Focal Dermal Hypoplasia ; Ribs ; Scoliosis ; Spinal Cord ; Women ; History ; Lost To Follow-up ; Diagnosis

INTRODUCTION

Lamellar ichthyosis (LI) is an inherited rare disorder characterized by generalized scaling presenting at birth and persisting throughout life. It presents at birth with a collodion membrane, later developing into large, brown scales across the skin. LI requires ongoing treatment and monitoring due to physical and psychosocial impacts. This study highlights siblings who showed substantial quality-of-life improvements with oral retinoid therapy.

OBJECTIVE

To present and discuss a detailed case summary, explore management options, and evaluate the treatment outcomes.

CASE SUMMARY

We report on a pair of siblings, a 24-year-old male and a 19-year-old female, who were born encased in a collodion membrane, and later presented with large, brown, plate-like scales all over the body. Skin changes were accompanied by intermittent heat intolerance and mild ectropion, which subsequently caused impaired quality of life while growing up. Histopathology results were consistent with lamellar ichthyosis. Both siblings responded well to oral Acitretin at 0.5 mglkglday, showing significant shedding of thick scales and a reduction of ectropion within the first two weeks of therapy.

CONCLUSION

Lamellar ichthyosis, a severe, lifelong disorder with psychosocial repercussions, requires long-standing, continual therapy. Maximizing treatment options with oral acitretin, addressing the psychosocial implications of the disease and getting patients actively involved in its management results in better treatment outcomes.

Human ; Male ; Female ; Young Adult: 19-24 Yrs Old ; Ichthyosis, Lamellar ; Acitretin

Lamellar Ichthyosis (LI) is a rare autosomal recessive disorder caused by mutations in genes, primarily TGM1, that affect skin barrier formation. It results in large, hyperpigmented, plate-like scales covering the entire body and persists throughout life. This case illustrates the chronic and debilitating nature of LI, highlights therapeutic approaches that improve quality of life, and emphasizes the importance of genetic testing in managing the condition.

Patient A, a 25-year-old female, and Patient B, a 22-year-old male, are Filipino siblings from non-consanguineous parents with no notable family history. Both were born encased in a collodion membrane that later revealed generalized erythema with large scales and deep fissures. As they aged, symptoms worsened, including reduced sweating, heat intolerance, ectropion, eclabium, cicatricial alopecia, palmoplantar hyperkeratosis, limited finger movement, and blurred vision from corneal scarring. Whole exome sequencing identified a homozygous pathogenic variant in the TGM1 gene (Arg396Cys). Their parents are carriers, giving future offspring a 25% risk of inheriting the condition. Acitretin therapy at 0.2 mg/kg/day, combined with topical keratolytics, led to significant improvement in symptoms and quality of life within four weeks.

Accurate diagnosis of ichthyosiform disorders requires thorough clinical documentation, family history, physical examination, and genetic findings. Effective management of lamellar ichthyosis needs a multidisciplinary approach, focusing on improving quality of life by addressing physical discomfort and social challenges. Genetic testing, especially Whole Exome Sequencing (WES), is crucial for precise diagnosis, genetic counseling, and informed family planning.

Human ; Male ; Female ; Adult: 25-44 Yrs Old ; Young Adult: 19-24 Yrs Old ; Ichthyosis, Lamellar

Junctional Epidermolysis Bullosa (JEB) is a rare inherited blistering disorder characterized by extreme skin fragility. It is associated with COL17A1 mutation that is critical for dermoepidermal adhesion. Effective management in resource-limited settings is challenging and focuses on wound care and trauma prevention to prevent complications and improve quality of life.

A 27-year-old Filipino female presented with recurrent blisters and erosions since infancy, accompanied by diffuse alopecia and anonychia of the toenails. On physical examination, she presented with multiple, well-defined, erythematous tense vesicles and bullae on the trunk, upper and lower extremities which were triggered by minor trauma to the skin. Skin punch biopsy was done revealing a subepidermal blistering dermatosis while direct immunofluorescence (DIF) and Enzyme-Linked Immunosorbent Assay (ELISA) tests for BP180, BP230, and type VII collagen were negative. Genetic testing was done and revealed compound heterozygous mutations in the COL17A1 gene, consistent with JEB. She was managed with non-adhesive dressings, sterile aspiration of blisters, and nutritional support. Despite the severity of her condition, the patient experienced significant improvement in wound healing and quality of life through meticulous wound care, trauma prevention and nutritional support.

This case highlights the unusual case of a 27-year-old Filipino female with JEB who has survived into adulthood, a rarity given the typically poor prognosis associated with severe forms of the disease.

Human ; Female ; Adult: 25-44 Yrs Old ; Epidermolysis Bullosa ; Quality Of Life

Dystrophic epidermolysis bullosa (DEB) is characterized by blisters that heal with scarring and milia formation, including nail dystrophy, with an incidence of 2.1 per million live births. DEB is derived from defects of the anchoring fibril which results in sublamina densa separation.

We report a one-month old female who presented with vesicles and erosions on bilateral feet at birth. New vesicles and bullae were noted on other areas of the body such as the scalp, ears, anterior trunk, gluteal area, and extremities which spontaneously ruptured leading to erosions and crusts. Nails were thick and yellowish black. Consult was done at a clinic and was given unrecalled antibiotic, antihistamine, and cream for one week. There was no noted improvement hence she was brought to another clinic, diagnosed as staphylococcal scalded skin syndrome, advised admission and subsequently referred to dermatology service. After clinical assessment, findings of cell poor subepidermal blister on histology, linear C3 on DIF, and positive collagen 7 on ELISA, patient was managed as a case of dystrophic epidermolysis bullosa.

Epidermolysis bullosa is an inherited genetic disease with mutation in COL7A1 gene manifesting as vesicles and bullae on trauma prone areas. The diagnosis is based on clinical, histopathology, immunofluorescence, antigen studies, and electron microscopy. Uniquely, immunofluorescence revealed strong linear deposition of C3 at the basement membrane zone which is more suggestive of bullous pemphigoid than epidermolysis bullosa. This case highlights the importance of early diagnosis and proper management of the disease to limit unnecessary intervention.

Human ; Female ; Infant: 1-23 Months ; Epidermolysis Bullosa Dystrophica ; Infant