Tuberous sclerosis complex (TSC) is a rare, autosomal dominant multisystem disorder affecting the brain, heart, kidneys, lungs, and skin leading to significant morbidity and mortality. We report a case of TSC and highlight the need for prompt diagnosis and proper surveillance to minimize life‑threatening complications. A 20‑year‑old female presented with facial and ungual papulonodular lesions 4 years after being diagnosed with epilepsy at the age of eight. No family history of genetic diseases was reported. Eight years later, the patient developed recurrent cough, shortness of breath, and blurring of vision. Biopsy of facial and digital nodule showed angiofibroma and ungual fibroma (Koenen tumor), respectively. Chest computed tomography scan revealed extensive cystic lesions diffusely scattered throughout the entire lung parenchyma suggestive of lymphangioleiomyomatosis. Cranial MRI revealed cortical and subependymal tubers, compatible with TSC. The patient had multidisciplinary management. However, her symptoms progressed, and she eventually succumbed to death. Cutaneous lesions such as facial angiofibromas and ungual fibromas along with multisystemic manifestations should alarm the clinician to TSC. Given its highly variable expressivity, awareness of different TSC‑associated signs and symptoms is essential for prompt diagnosis, proper treatment, disease monitoring, and early recognition of TSC complications.
Angiofibroma ; Lymphangioleiomyomatosis ; Tuberous Sclerosis

OBJECTIVE: To explore the clinical characteristics and genetic variants in two children with Tuberous sclerosis complex (TSC). METHODS: Two children who had presented at the Children's Hospital Affiliated to Zhengzhou University respectively in June 2020 and July 2021 were selected as the study subjects. Clinical data of the children were collected, and potential pathogenic variants were screened by whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of their family members. RESULTS: Child 1 was a 7-month-and-29-day-old male, and child 2 was a 2-year-and-6-month-old male. Both children had shown symptoms of epileptic seizures and multiple hypomelanotic macules. Genetic testing revealed that both children had harbored de novo variants of the TSC2 gene, namely c.3239_3240insA and c.3330delC, which were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION This study has uncovered the genetic etiology for two children with TSC. Above findings have also enriched the phenotypic and mutational spectrum of TSC in the Chinese population.
Humans ; Infant ; Male ; Family ; Genetic Testing ; Genomics ; Mutation ; Tuberous Sclerosis/genetics* ; Child, Preschool ; East Asian People

Humans ; Tuberous Sclerosis/therapy*

INTRODUCTION: Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder causing a mutation in the tumor suppressor genes, TSC1 or TSC2. Loss of function of these genes leads to dysfunction of hamartin and tuberin, resulting in hamartoma formation. It usually manifests with cutaneous manifestations at childhood. However, it also affects other organ systems. Based on the Philippine Dermatological Society Health Information System census, there have been 104 cases of TSC from 2011-2018. Currently, limited data is available regarding the treatment options in the local setting.

CASE REPORT: The case involves a 4 year-old boy, with a two year history of flesh-colored to dusky red fi rm papules on the centrofacial areas and neck. Lesions have been increasing in number since first appearance. He had a normal birth history. Family history was insignificant. However, delay in expressive speech development was noted. Physical examination revealed multiple well-defined angiofibromas on centrofacial areas and neck; fibrous cephalic plaque on the left temporal area, and several ash-leaf spots on the trunk. Periungual and subungual fibromas, confetti macules, shagreen patch and dental pits were absent. Based on the clinical manifestations, he was diagnosed with TSC. Histopathology of a papule on the chin was consistent with angiofibroma. Parents were concerned with the appearance of the lesions and preferred conservative management. Hence, topical sirolimus 0.2% ointment was applied once daily on the angiofibromas for 4 months. Monthly follow-up showed marked improvement, manifested by the decrease in number and by flattening of the lesions.

CONCLUSION: To the best of our knowledge, this is the fi rst case report of successful treatment of topical sirolimus for TSC in the Philippines.

KEYWORDS: tuberous sclerosis complex, topical, treatment success, conservative management, hematoma

OBJECTIVE: To analyze variants of TSC1 and TSC2 genes in a Chinese patient with tuberous sclerosis complex (TSC). METHODS: Peripheral blood samples were collected from the patient and her parents with informed consent. Following extraction of genomic DNA, potential variants of the TSC1 and TSC2 genes was detected by using targeted capture next-generation sequencing (NGS) and Sanger sequencing. RESULTS: The patient was found to harbor a de novo mosaicism variant c.3295_3298delG (Val1100CysfsTer3) of the TSC2 gene, with the proportion of the mutant allele determined as 13.4%, which was confirmed by Sanger sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.3295_3298delG (Val1100CysfsTer3) variant was predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION The mosaicism heterozygous variant of c.3295_3298delG of the TSC2 gene, as detected by both NGS and Sanger sequencing, probably underlay the TSC2 in this patient.
Female ; Humans ; Mosaicism ; Mutation ; Tuberous Sclerosis/genetics* ; Tuberous Sclerosis Complex 1 Protein/genetics* ; Tuberous Sclerosis Complex 2 Protein/genetics*

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with tuberous sclerosis complex (TSC). METHODS: The TSC1 and TSC2 genes were sequenced. Candidate variant was verified by Sanger sequencing of the proband and her family members. Pathogenicity of the variant was predicted based on the American College of Medical Genetics and Genomics (ACMG) guidelines. RESULTS: The proband was found to harbor a heterozygous c.52delC frameshift variant of the TSC2 gene, which may result in synthesis of amino acid chain starting from the 18th amino acid Leu and terminating at the 28th amino acid (p.Leu18CysfsTer28). The variant was unreported in the public database. Mutation Taster software predicted that the variant is harmful. Both parents of the proband were of the wild type, suggesting that the variant has occurred de novo. Based on the ACMG guidelines, the variant was predicted to be likely pathogenic (PVS1 +PM2). CONCLUSION A novel pathogenic variant of the TSC2 gene c.52delC (p.Leu18CysfsTer28) was identified, which has enriched the mutational spectrum of TSC2 and provided a basis for genetic counseling for this pedigree.
Humans ; Female ; Tuberous Sclerosis/pathology* ; Tuberous Sclerosis Complex 2 Protein/genetics* ; Pedigree ; Mutation ; Amino Acids/genetics* ; China

OBJECTIVE: To explore the clinical characteristics and genetic variant in a neonate with tuberous sclerosis complex (TSC). METHODS: Clinical data of the neonate was collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to next-generation sequencing (NGS). RESULTS: The child was noted to have yellowish hair upon birth. NGS revealed that he has harbored a heterozygous c.3914del (p.P1305Rfs*20) frameshifting variant of the TSC2 gene. The variant has probably caused premature termination of translation, resulting in a truncated protein. CONCLUSION Yellowish hair has rarely been described as the first manifestation of TSC. The c.3914del (p.P1305Rfs*20) variant of the TSC2 gene probably underlay the TSC in this patient.
Male ; Infant, Newborn ; Humans ; Tuberous Sclerosis/genetics* ; Family ; Carotenoids ; Heterozygote

Fibroma/diagnostic imaging* ; Humans ; Odontogenic Tumors/diagnostic imaging* ; Tuberous Sclerosis/complications*

OBJECTIVE: To explore the genetic basis for Chinese pedigree affected with tuberous sclerosis complex (TSC). METHODS: The proband and his family members were subjected to Sanger sequencing for variants of the TSC1 and TSC2 genes. RESULTS: The proband was found to harbor a c.2837+1dupG splicing variant at a donor site of the TSC2 gene. The same variant was not found among his family members and the fetus during his mother's subsequent pregnancy. CONCLUSION The c.2837+1dupG splicing variant of the TSC2 gene has probably predisposed to the TSC in this pedigree. Above finding has enriched the spectrum of pathogenic variants associated with this disease.
Female ; Genetic Testing ; Humans ; Male ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Tuberous Sclerosis/genetics* ; Tuberous Sclerosis Complex 2 Protein/genetics*

OBJECTIVE: To analyze the clinical features of a Chinese pedigree affected with tuberculosis sclerosis and explore its molecular pathogenesis. METHODS: Clinical data of the proband and members of his pedigree were collected. Whole exome sequencing was carried out to detect variants of the TSC1 and TSC2 genes. Candidate variants was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The proband and his mother, who also had mild features of tuberous sclerosis, were found to harbor a novel heterozygous c.4183C>T (p.Q1395X) variant of the TSC2 gene, which was absent in the 4 healthy relatives. Bioinformatic analysis suggested the variant to be likely pathogenic. CONCLUSION The heterozygous c.4183C>T (p.Q1395X) variant of the TSC2 gene probably underlay the disease in this pedigree. Above finding has expanded the spectrum of TSC2 gene variants. The more severe symptoms in the proband may be attributed to phenotypic heterogeneity of this disease.
China ; Humans ; Mutation ; Pedigree ; Tuberous Sclerosis/genetics* ; Tuberous Sclerosis Complex 2 Protein/genetics*