OBJECTIVE: To provide preimplantation genetic testing (PGT) for a patient with Incontinentia pigmenti (IP) due to IKBKG gene variant but without family samples through construction of single nucleotide polymorphism (SNP)-based haplotype by Long-read sequencing (LRS) technology. METHODS: A female IP patient with a heterozygous IKBKG c.1167dup variant but without family genetic data who sought genetic counseling at Women and Children' Hospital of Ningbo University in November 2021 was selected as the study subject. The IKBKG gene has a highly homologous pseudogene IKBKGP1. Genomic DNA was extracted from peripheral blood samples from the couple, and LRS was used to obtain informative SNP loci flanking the variant locus, enabling the construction of SNP haplotype with a long segment spanning from the non-homologous region of IKBKG to the variant site. Trophoblast cells were biopsied from blastocysts fertilized through intracytoplasmic sperm injection, and next-generation sequencing (NGS) was used to determine the SNP information of the embryos. Linkage analysis with the parental SNP haplotypes was conducted to detect the carrier status of the embryos and exclude chromosomal aneuploidies. Sanger sequencing was carried out to validate the result. A euploid embryo without the pathogenic variant was selected for transfer. Prenatal diagnosis was carried out by amniocentesis at mid-trimester to verify the result of PGT tests, and follow-up was conducted after the baby was born. This study has been approved by the Ethics Committee of Women and Children's Hospital of Ningbo University (Ethics No. EC2023-094). RESULTS: A total of seven blastocysts were tested, and PGT results indicated that two embryos were euploid and did not carry the pathogenic variant. One euploid embryo was transferred, which resulted in a singleton pregnancy. Amniocentesis at 24 weeks of gestation confirmed that the status of fetal IKBKG gene, and its chromosomal status was consistent with the PGT results. A healthy male infant was born at 38+6 weeks of gestation. CONCLUSION For IP patients with de novo mutation or without family genetic samples, PGT with LRS can directly construct the SNP-based haplotype while avoiding interference from pseudogenes, providing an effective strategy for PGT.
Female ; Humans ; Male ; Pregnancy ; Genetic Testing/methods* ; Haplotypes/genetics* ; High-Throughput Nucleotide Sequencing/methods* ; I-kappa B Kinase/genetics* ; Incontinentia Pigmenti/diagnosis* ; Polymorphism, Single Nucleotide/genetics* ; Preimplantation Diagnosis/methods* ; Infant, Newborn

The purpose of this study is to report a successful twin pregnancy and delivery in a female patient with X-linked dominant incontinentia pigmenti (IP) who underwent assisted reproductive technology followed by preimplantation genetic screening (PGS). A 29-year-old female with IP had a previous history of recurrent spontaneous abortion. A molecular analysis revealed the patient had a de novo mutation, 1308_1309insCCCCTTG(p.Ala438ProfsTer26), in the inhibitor of the kappa B kinase gamma gene located in the Xq28 region. IVF/ICSI and PGS was performed, in which male embryos were sexed using array-based comparative genomic hybridization (aCGH). After IVF/ICSI and PGS using aCGH on seven embryos, two euploid male blastocysts were transferred with a 50% probability of a viable male pregnancy. The dizygotic twin pregnancy was confirmed and the amniocentesis results of each twin were normal with regard to the mutation found in the mother. The patient delivered healthy twin babies during the 37th week of gestation. This case shows the beneficial role of PGS in achieving a successful pregnancy through euploid male embryo gender selection in a woman with X-linked dominant IP with a history of multiple male miscarriages.
Abortion, Habitual ; Abortion, Spontaneous ; Adult ; Amniocentesis ; Blastocyst ; Comparative Genomic Hybridization ; Embryonic Structures ; Female ; Genetic Testing* ; Humans ; Incontinentia Pigmenti* ; Male ; Mothers ; Phosphotransferases ; Pregnancy ; Pregnancy, Twin ; Preimplantation Diagnosis ; Reproduction* ; Reproductive Techniques, Assisted ; Twins, Dizygotic ; X Chromosome

Female ; Humans ; Incontinentia Pigmenti ; diagnosis ; pathology ; therapy ; Infant, Newborn

Incontinentia pigmenti (IP) is an uncommon genodermatosis that usually occurs in female infants. It is characterized by ectodermal, mesodermal, neurological, ocular, and dental manifestations. The aim of this study was to clarify clinical symptoms, accompanying diseases, and complications of IP. Forty cases of IP have been reviewed by their medical records, laboratory data, clinical photographs, and telephone survey. Male-to-female ratio was 1 to 19 and their onsets were mostly in utero. They were usually diagnosed during the neonatal period owing to their early expression of skin manifestation. Central nervous system anomalies were found in 46.7%. Ocular disorders and dental defects were detected in 66.7% and 72.7% respectively. The most commonly diagnosed anomalies were hypodontia, retinopathy, and seizure. For better understanding of IP, long term and close cooperation between dermatologists, pediatricians, neuroscientists, genentic counselors, and even dentists is crucial.
Stomatognathic Diseases/complications ; Skin Diseases/complications ; Male ; Magnetic Resonance Imaging/methods ; Korea ; Infant, Newborn ; Infant ; Incontinentia Pigmenti/*diagnosis/pathology ; Humans ; Female ; Eye Diseases/complications ; Eosinophilia/complications ; Child, Preschool ; Child ; Central Nervous System Diseases/complications

Incontinentia pigmenti is a rare neurocutaneous syndrome characterized by vesiculobullous skin disease in neonates and infants, a noninfectious disease that should be distinguished from infectious diseases with the neonatal seizure or encephalopathy. This disease is X-linked dominant with Xq28 region abnormalities and often associated with developmental defects of the ocular, skeletal, dental, and central nervous system. Central nervous system involvement in the neonatal period, or complicated by encephalopathy, may cause severe neurologic impairment, retardation or even death. We experienced a case of incontinentia pigmenti in a three-day-old female patient who had characteristic papulovesicular skin lesions and partial seizures with secondary generalization. Histopathological examination favored the diagnosis of incontinentia pigmenti and a brain MRI showed undifferentiated white matters with periventricular nodular lesions.
Brain* ; Central Nervous System ; Communicable Diseases ; Diagnosis ; Female ; Generalization (Psychology) ; Humans ; Incontinentia Pigmenti* ; Infant ; Infant, Newborn ; Magnetic Resonance Imaging ; Neurocutaneous Syndromes ; Seizures ; Skin ; Skin Diseases, Vesiculobullous

Incontinentia pigmenti(IP) is an X-linked dominantly inherited disorder with female predominance. Skin lesions are characterized by three or four stages; vesicobullous, verrucous, hyperpigmented and hypopigmented lesions. About 80% of patients with incontinentia pigmenti have one or more associated ectodermal or mesodermal anomalies involving teeth, nail, hair, eye, breast, bones and nervous system. A newborn girl had erythematous based vesicles and bullae on her trunk and extremities with peripheral eosinophilia. Within several days, she showed linear verrucous plaques. A skin biopsy specimen showed eosinophilic spongiosis in the epidermis and numerous eosinophils in the dermis. The diagnosis of IP was made. She was revealed to have some congenital heart anomalies; atrial septal defect (ASD) and patent ductus arteriosus(PDA). Cases of IP with congenital heart disease have been reported very rarely. Therefore, we report this unique case of IP associated with ASD and PDA.
Biopsy ; Breast ; Dermis ; Diagnosis ; Ectoderm ; Eosinophilia ; Eosinophils ; Epidermis ; Extremities ; Female ; Hair ; Heart Defects, Congenital ; Heart Diseases* ; Heart Septal Defects, Atrial ; Heart* ; Humans ; Incontinentia Pigmenti* ; Infant, Newborn ; Mesoderm ; Nervous System ; Skin ; Tooth

Becker muscular dystrophy is a X-linked recessive disease with the affected gene at locus Xp21, characterized by progressive muscular weakness. Without the definite family history, it has been known that the diagnosis of this disease is almost impossible on clinical grounds alone. We reviewed the muscle pathology of two casses of genetically confirmed Becker muscular dystrophy to know the diagnositc significances of this study. The first case, a 20 year old man, is the classical one with definite family history of X-linked recessive heredity. The muscle pathology of the biceps showed dystrophic muscular changes, including increased internal nuclei, marked variation of fiber sizes and mild endomysial fibrosis. The dystrophin stain of the muscle was also confirmative for the diagnosis. The second case was a 32 year old man who has been biopsied his left vastus lateralis 5 years before this genetic diagnosis. This case is a sporadic one without the family history. The diagnosis at the time of muscle biopsy was limb-girdle muscular dystorphy or inclusion body myositis because of the typical rimmed vacuoles and marked variation of fiber sizes. The dystophin stain was not available at that time. Our conclusion is that the molecular genetic study and/or dystrophin protein test of muscle biopsy should be done in every clinically suspected patient, including limb-girdle muscular dystorphy, inclusion body myositis or rimmed vacuolar myopathies.
Adult ; Biopsy ; Diagnosis ; Dystrophin ; Fibrosis ; Heredity ; Humans ; Incontinentia Pigmenti* ; Molecular Biology ; Muscle Weakness ; Muscular Diseases ; Muscular Dystrophy, Duchenne ; Myositis, Inclusion Body ; Pathology ; Quadriceps Muscle ; Vacuoles ; Young Adult

Incontinentia pigmenti (IP) is a rare hereditary neurocutaneous syndrome characterized by typical linear hyperpigmentationed skin lesions, often associated with central nervous system (CNS) involvement, dysplasia in dental and skeletal system, and ocular abnormalities. Thirty to fifty percent of the patients suffer CNS complications such as mental retardation, seizures, spastic paralysis, microcephaly, and cerebellar ataxia. We experienced a case of incontinentia pigmenti in three-month-old female patient who had characteristic linear hyperpigmented skin lesion on both her thighs and partial seizure with secondary generalization. She had family history of typical skin lesions on her maternal relatives. She showed abnormal findings on EEG as well as multiple necrotic lesions on brain MRI. Confirm diagnosis of incontinentia pigmenti was made by skin biopsy.
Biopsy ; Brain ; Central Nervous System ; Cerebellar Ataxia ; Diagnosis ; Electroencephalography ; Female ; Generalization (Psychology) ; Humans ; Incontinentia Pigmenti ; Intellectual Disability ; Magnetic Resonance Imaging ; Microcephaly ; Muscle Spasticity ; Muscular Dystrophy, Duchenne* ; Neurocutaneous Syndromes ; Paralysis ; Pathology* ; Seizures ; Skin ; Thigh

Incontinentia pigmenti is an uncommon genodermatosis. It affects female infants predominantly, described first by Bardach in l925, with the diagnosis of systematized nevus and Bloch in 1926, and Sulzberger in 1928 rnore compIetely. Skin lesions are characterized by 3 stages such as vesicobullous, verucous and finally pigmentary lesions and leave brownish pigmentation on the extremities and trunk. Hesides skin lesions some ectodermaI and mesodermal organs are affected and show developmental abnormalities. We experienced a case of incontinentia pigmenti in a 45-day-old female infant and present it with the review of literature. She showed extensive vesicobullopustular eruption with linear and reticular pigmentation on the extremities and trunk. Clinical and histopathologic findings of these lesions are compatible with Bloch-Sulzberger type of incontinentia pigmenti.
Diagnosis ; Extremities ; Female ; Humans ; Incontinentia Pigmenti* ; Infant ; Mesoderm ; Nevus ; Pigmentation ; Skin

Five cases of incontinentia pigmenti (Bloch-Sulzberge type) were presented and literature were reviewed. They were all girls. 3cases of them were associated with defects of ectodermal or mesodermal development. As the manifestation of those, malformed teeth in 2 cases, delayed dentition in 3 cases, eye problem in 2 cases, and alopecia in 3 cases were noticed. One of 3 cases had eruptions of lichen striatus on her upper extremities. Especially, family history of involvement of maternal relative in one case was noticed. Diagnosis of them were confirmed by characteristic clinical appearance and histopathologic findings.
Alopecia ; Dentition ; Diagnosis ; Ectoderm ; Female ; Humans ; Incontinentia Pigmenti ; Lichens ; Mesoderm ; Tooth ; Upper Extremity