RARE DISEASE
Pfeiffer syndrome
Pfeiffer syndrome
Pfeiffer syndrome
Synonyms: ACS5, Acrocephalosyndactyly type 5
Synonyms: ACS5, Acrocephalosyndactyly type 5
Synonyms: ACS5, Acrocephalosyndactyly type 5
Drug discovery
161
papers
On emerging therapies
Overview
Pfeiffer syndrome is a rare autosomal dominant genetic disorder caused by FGFR1 or FGFR2 mutations, characterized by craniosynostosis, midface hypoplasia, and limb anomalies (broad thumbs/great toes, partial syndactyly). Three subtypes exist: Type 1 (mild, normal cognition), Type 2 (cloverleaf skull, severe neurovascular risks), and Type 3 (severe sans cloverleaf). Complications include airway obstruction, hydrocephalus, vision/hearing loss, and Chiari malformation [1][4][10].
Burden
Therapies
Early cranial vault surgery (decompression, distraction osteogenesis) to manage intracranial pressure [3][12].
Multidisciplinary care: craniofacial reconstruction, tracheostomy for airway compromise, and syndactyly correction [3][8][18].
Long-term management of sleep apnea, dental malocclusion, and developmental delays [1][14].
Categories: rare bone diseases, rare developmental anomalies during embryogenesis, rare genetic diseases, rare ophthalmic disorders
Research Papers
161 drug discovery papers about Pfeiffer syndrome. Recent publications:
161 drug discovery papers about Pfeiffer syndrome. Recent publications:
categories:
Small molecules
small molecules
2026-01-01 | PFEIFFER SYNDROME TYPE 2 IN A NEWBORN: CLINICAL CASE, NEUROIMAGING, AND EARLY REHABILITATION
МЦНП «НОВАЯ НАУКА» СИНДРОМ ПФАЙФФЕРА 2 ТИПА У НОВОРОЖДЁННОГО: КЛИНИЧЕСКИЙ СЛУЧАЙ, НЕЙРОВИЗУАЛИЗАЦИЯ И РАННЯЯ РЕАБИЛИТАЦИЯ Обидов Хусейн Хошимович ординатор-невролог Давлатов Мирзонозим Девонакулович ординатор-невролог Научный руководитель: Нуриева Айгуль Темирзагитовна ассистент кафедры неврологии ФГБОУ ВО «БГМУ» Минздрава России, заведующий отделением медицинской реабилитации № 2 ГБУЗ РБ ГДКБ № 17 Аннотация: Актуальность.Синдром Пфайффера (PS) -редкое аутосомно-доминантное заболевание из группы краниосиностозов, обусловленное мутациями в генах «FGFR1/FGFR2».Тип 2 является наиболее тяжёлым вариантом, характеризующимся черепом в форме «трилистника», внутренней окклюзионной гидроцефалией, гипоплазией средней зоны лица и высоким риском летальности в раннем возрасте.Цель.На основе клинического наблюдения охарактеризовать фенотипические проявления, данные нейровизуализации и результаты ранней медицинской реабилитации при синдроме Пфайффера типа 2 у новорождённого. Материалы и методы.Проведён ретроспективный анализ деидентифицированной медицинской документации пациентки в возрасте 1 месяц 2 дня с клинически верифицированным синдромом Пфайффера типа 2. Использованы клинические, инструментальные (компьютерная томография головного мозга с 3D-реконструкцией, нейросонография, эхокардиография) и лабораторные методы.Результаты.У пациентки выявлен полный диагностический комплекс синдрома Пфайффера 2 типа: краниосиностоз с формированием черепа в виде «трилистника», внутренняя гидроцефалия (боковые желудочки до 26 мм, III желудочек 12 мм), перивентрикулярный отёк, гипоплазия средней зоны лица, экзофтальм.Диагностированы сопутствующие пороки развития: дефект МЦНП «НОВАЯ НАУКА» межжелудочковой перегородки, открытый артериальный проток, ангиопатия сетчатки.Проведён курс ранней реабилитации (войта-терапия, диакарб, аспаркам).Отмечена положительная динамика в виде прироста массы тела и уменьшения вегетативных дисфункций.Заключение.Синдром Пфайффера 2 типа требует мультидисциплинарного подхода с ранним нейрохирургическим вмешательством.Необходима генетическая верификация (FGFR2) и этапная реабилитация.
2022-03-21 | Case Report: Anisometropic Astigmatism Secondary to Unilateral Coronal Synostosis.
This case highlights the importance of performing a cycloplegic examination, including retinoscopy, on infants with the diagnosis of craniosynostosis because of the risk of refractive amblyopia. This report presents the unique case of an infant with amblyogenic anisometropic astigmatism secondary to unilateral coronal synostosis, which resolved after fronto-orbital advancement. A 4-month, 14-day-old male infant with right unilateral coronal synostosis associated with Pfeiffer syndrome presented to the clinic with anisometropic astigmatism (right eye, +2.00 diopter sphere; left eye, +4.00 -4.75 ×170). Because of his young age, this refractive error was initially monitored. Upon follow-up examination at 6 months of age, he showed stability in his refractive error and early signs of amblyopia. Glasses were prescribed and amblyopia resolved. After cranial surgery, the patient's orbits were symmetric, and his amblyogenic astigmatism resolved. Patients who present to the clinic with craniosynostosis should undergo cycloplegic examinations, including retinoscopy, early in their care with the knowledge that these patients can require interventions such as glasses and amblyopia treatment.
2018-11-14 | Up-regulation of fibroblast growth factor receptor 1 due to prenatal tobacco exposure can lead to developmental defects in new born
Introduction: Tobacco-smoking is one of the most important risk factor for preterm delivery, pregnancy loss, low birth weight, and fetal growth restriction. It is estimated that approximately 30% of growth-restricted neonates could be independently associated with maternal smoking.Methods: In this study, gene expression profile, GSE11798, was chosen from GEO database with an aim to perceive change in gene expression signature in new born due to maternal smoking. Enrichment analysis was performed to annotate differentially expressed genes (DEGs) through gene ontology and pathway analysis using DAVID. Protein–protein interactions and module detection of these DEGs were carried out using cytoscape v3.6.0. Thirty umbilical cord tissue samples from 15 smokers and 15 non-smokers pregnant women were included in this analysis.Results: Twenty-six differentially expressed genes (DEGs) between two groups were selected using GEO2R tool. The DEGs were observed to be participating in biological processes/pathways related to growth releasing hormone, angiogenesis, embryonic skeletal, and cardiac development. Fibroblast growth factor receptor-1 (FGFR1) was identified to be the hub node with 348 interacting partners, which regulates transcription, cell growth, differentiation, and apoptosis. The up-regulation of FGFR1 in umbilical cord tissue may lead to reproductive and developmental complications such as encephalocraniocutaneous lipomatosis, osteoglophonic dysplasia, and Pfeiffer syndrome in new-borns.Conclusion: The findings manifests the possibility of overcoming these adverse health effects in new born through FGFR1 modulating treatments during pregnancy.
2017-08-18 | ARQ 087 inhibits FGFR signaling and rescues aberrant cell proliferation and differentiation in experimental models of craniosynostoses and chondrodysplasias caused by activating mutations in FGFR1, FGFR2 and FGFR3
Tyrosine kinase inhibitors are being developed for therapy of malignancies caused by oncogenic FGFR signaling but little is known about their effect in congenital chondrodysplasias or craniosynostoses that associate with activating FGFR mutations. Here, we investigated the effects of novel FGFR inhibitor, ARQ 087, in experimental models of aberrant FGFR3 signaling in cartilage. In cultured chondrocytes, ARQ 087 efficiently rescued all major effects of pathological FGFR3 activation, i.e. inhibition of chondrocyte proliferation, loss of extracellular matrix and induction of premature senescence. In ex vivo tibia organ cultures, ARQ 087 restored normal growth plate architecture and eliminated the suppressing FGFR3 effect on chondrocyte hypertrophic differentiation, suggesting that it targets the FGFR3 pathway specifically, i.e. without interference with other pro-growth pathways. Moreover, ARQ 087 inhibited activity of FGFR1 and FGFR2 mutants associated with Pfeiffer, Apert and Beare-Stevenson craniosynostoses, and rescued FGFR-driven excessive osteogenic differentiation in mouse mesenchymal micromass cultures or in ex vivo calvarial organ cultures. Our data warrant further development of ARQ 087 for clinical use in skeletal disorders caused by activating FGFR mutations.
2017-05-10 | A Case of Pediatric Post-Traumatic Stress Disorder Presenting as Attention Deficit Hyperactivity Disorder: A Case Report
In the past few years, there has been increased recognition that children, who have faced traumatic incidences, can develop post-traumatic stress disorder (PTSD), just like in adults. We present a case of PTSD in a 6-year-old child who endured three surgical procedures because he was suffering from a congenital cranial stenosis (Pfeiffer) syndrome. Because of repetitive painful episodes, resulting from the syndrome, and then post-surgical complications, the child developed behavioral outbursts, hypervigilence, concentration problems, and irritability. In the past, the child was diagnosed with attention deficit hyperactivity disorder (ADHD) in the realm of his behavioral complaints, and he was already on stimulant medications for last one year. But there was no remarkable effect of pharmacotherapy on child's behavior despite increasing dosages. Ultimately the child's medical and psychiatric history was reviewed and a diagnosis of pediatric PTSD was made. Stimulant medications were discontinued and management was started on the lines of pediatric PTSD, resulting in a remarkable improvement in child's psychiatric outcome.
gene therapies
2026-04-24 | The Clinical and Molecular Spectrum of Turkish Patients with Syndromic Craniosynostosis: A Single Center Study
Objective: Syndromic craniosynostosis is caused by pathogenic variants in genes regulating suture development. This study aims to investigate clinical and molecular characteristics in syndromic craniosynostosis. Materials and Methods: This retrospective descriptive study included 53 patients from 40 families with syndromic craniosynostosis. Molecular testing was performed in 22 families. Results: The study included Saethre-Chotzen (n=14), Apert (n=12), Crouzon (n=11), Pfeiffer (n=4), Muenke (n=4), and Carpenter (n=1) syndromes, Crouzon syndrome with acanthosis nigricans (n=2), craniosynostosis with dental anomalies (n=2), craniosynostosis type 4 (n=2), and hypochondroplasia with craniosynostosis (n=1). Genetic etiology was identified in 20 families involving six genes: FGFR1 (Pfeiffer), FGFR2 (Apert, Crouzon, Pfeiffer), FGFR3 (Crouzon with acanthosis nigricans, Muenke), TWIST1 (Saethre-Chotzen), ERF (Craniosynostosis type 4), and IL11RA (Craniosynostosis with dental anomaly). Additionally, a FGFR3 variant causing hypochondroplasia was identified in a patient with multisuture synostosis. Familial inheritance was identified in 25%, but not in Apert syndrome. Brachycephaly (28.3%) was the most common cranial abnormality, followed by plagiocephaly (22.6%). Apert syndrome was characterized by frequent cardiac anomalies, cleft palate, developmental delay, and a higher rate of surgical intervention. In contrast, Crouzon, Pfeiffer, Saethre–Chotzen, and Muenke syndromes showed favorable outcomes, although a fatal course was observed in a patient with Crouzon syndrome with acanthosis nigricans. Rare etiologies included ERF-related craniosynostosis with mild craniofacial findings and IL11RA-related craniosynostosis with intrafamilial phenotypic heterogeneity. Conclusion: This study describes clinical features of well-defined syndromes such as Apert, Crouzon, and Pfeiffer; reports craniosynostosis in hypochondroplasia; and documents rare ERF- and IL11RA-related forms, highlighting the importance of combining clinical and molecular diagnostics.
2026-02-18 | Prenatal and Postmortem Characterization of FGFR2-Related Fetal Craniosynostosis: Emphasizing Rare and Atypical Anomalies.
Craniosynostosis (CS) is the second most common craniofacial birth defect after orofacial clefts. Genetic counseling is essential for reproductive planning in affected families. Nine fetal CS cases-six Apert syndrome (AS) and three Pfeiffer syndrome (PS)-with established genetic causes were retrospectively analyzed for clinical, radiological, and molecular features. Mean gestational age at first examination was 26.2 weeks. Four AS and two PS cases were diagnosed during the prenatal stage by ultrasonography (USG), whereas two AS and one PS cases were identified during postmortem. Common prenatal findings included polyhydramnios, high flat forehead, and syndactyly. Two of the three cases diagnosed at the postmortem stage had multiple congenital anomalies (MCA), while in the third, CS was suspected due to frontal bossing and proptosis despite the absence of classic signs. All cases carried pathogenic FGFR2 variants. Proptosis, frontal bossing, and trigonocephaly are key prenatal indicators of CS, but their absence-especially with systemic anomalies-can challenge diagnosis. In cases with MCA, CS should be suspected even if classic signs are absent, particularly when syndactyly accompanies other complex abnormalities. Postmortem evaluation and molecular genetic testing are essential for definitive diagnosis, especially when clinical features are ambiguous.
2025-05-20 | A Rare Case of Prenatally Diagnosed Pfeiffer Syndrome with Multicystic Kidney.
Pfeiffer syndrome is a rare syndromic craniosynostosis characterized by bilateral coronal craniosynostosis, midface hypoplasia, beaked nasal tip, broad and medially deviated thumbs and great toes. It is caused by mutations affecting the fibroblast growth factor receptors type 1 or 2 (FGFR1 or FGFR2), with autosomal dominant inheritance. It displays substantial clinical and genetic heterogeneity. The disorder is usually detected in the neonatal period, and very few prenatally diagnosed cases have been reported.
2023-07-31 | Molecular Scalpels: The Future of Pediatric Craniofacial Surgery?
CRISPR-Cas genome editing tools are among the most substantial advances in the life sciences in modern history. Single-dose gene therapies to correct pathogenic mutations have moved quickly from bench to bedside, with several therapeutics designed by CRISPR pioneers entering various stages of clinical investigation. Applications of these genetic technologies are poised to reshape the practice of both medicine and surgery. Many of the most morbid conditions treated by craniofacial surgeons are syndromic craniosynostoses caused by mutations in fibroblast growth factor receptor genes, including Apert, Pfeiffer, Crouzon, and Muenke syndromes. The fact that pathogenic mutations in these genes are recurrent in the majority of affected families presents a unique opportunity to develop "off-the-shelf" gene editing therapies to correct these mutations in affected children. The therapeutic potential of these interventions could reshape pediatric craniofacial surgery, potentially first eliminating the need for midface advancement procedures in affected children.
small molecules
2026-01-01 | PFEIFFER SYNDROME TYPE 2 IN A NEWBORN: CLINICAL CASE, NEUROIMAGING, AND EARLY REHABILITATION
МЦНП «НОВАЯ НАУКА» СИНДРОМ ПФАЙФФЕРА 2 ТИПА У НОВОРОЖДЁННОГО: КЛИНИЧЕСКИЙ СЛУЧАЙ, НЕЙРОВИЗУАЛИЗАЦИЯ И РАННЯЯ РЕАБИЛИТАЦИЯ Обидов Хусейн Хошимович ординатор-невролог Давлатов Мирзонозим Девонакулович ординатор-невролог Научный руководитель: Нуриева Айгуль Темирзагитовна ассистент кафедры неврологии ФГБОУ ВО «БГМУ» Минздрава России, заведующий отделением медицинской реабилитации № 2 ГБУЗ РБ ГДКБ № 17 Аннотация: Актуальность.Синдром Пфайффера (PS) -редкое аутосомно-доминантное заболевание из группы краниосиностозов, обусловленное мутациями в генах «FGFR1/FGFR2».Тип 2 является наиболее тяжёлым вариантом, характеризующимся черепом в форме «трилистника», внутренней окклюзионной гидроцефалией, гипоплазией средней зоны лица и высоким риском летальности в раннем возрасте.Цель.На основе клинического наблюдения охарактеризовать фенотипические проявления, данные нейровизуализации и результаты ранней медицинской реабилитации при синдроме Пфайффера типа 2 у новорождённого. Материалы и методы.Проведён ретроспективный анализ деидентифицированной медицинской документации пациентки в возрасте 1 месяц 2 дня с клинически верифицированным синдромом Пфайффера типа 2. Использованы клинические, инструментальные (компьютерная томография головного мозга с 3D-реконструкцией, нейросонография, эхокардиография) и лабораторные методы.Результаты.У пациентки выявлен полный диагностический комплекс синдрома Пфайффера 2 типа: краниосиностоз с формированием черепа в виде «трилистника», внутренняя гидроцефалия (боковые желудочки до 26 мм, III желудочек 12 мм), перивентрикулярный отёк, гипоплазия средней зоны лица, экзофтальм.Диагностированы сопутствующие пороки развития: дефект МЦНП «НОВАЯ НАУКА» межжелудочковой перегородки, открытый артериальный проток, ангиопатия сетчатки.Проведён курс ранней реабилитации (войта-терапия, диакарб, аспаркам).Отмечена положительная динамика в виде прироста массы тела и уменьшения вегетативных дисфункций.Заключение.Синдром Пфайффера 2 типа требует мультидисциплинарного подхода с ранним нейрохирургическим вмешательством.Необходима генетическая верификация (FGFR2) и этапная реабилитация.
2022-03-21 | Case Report: Anisometropic Astigmatism Secondary to Unilateral Coronal Synostosis.
This case highlights the importance of performing a cycloplegic examination, including retinoscopy, on infants with the diagnosis of craniosynostosis because of the risk of refractive amblyopia. This report presents the unique case of an infant with amblyogenic anisometropic astigmatism secondary to unilateral coronal synostosis, which resolved after fronto-orbital advancement. A 4-month, 14-day-old male infant with right unilateral coronal synostosis associated with Pfeiffer syndrome presented to the clinic with anisometropic astigmatism (right eye, +2.00 diopter sphere; left eye, +4.00 -4.75 ×170). Because of his young age, this refractive error was initially monitored. Upon follow-up examination at 6 months of age, he showed stability in his refractive error and early signs of amblyopia. Glasses were prescribed and amblyopia resolved. After cranial surgery, the patient's orbits were symmetric, and his amblyogenic astigmatism resolved. Patients who present to the clinic with craniosynostosis should undergo cycloplegic examinations, including retinoscopy, early in their care with the knowledge that these patients can require interventions such as glasses and amblyopia treatment.
2018-11-14 | Up-regulation of fibroblast growth factor receptor 1 due to prenatal tobacco exposure can lead to developmental defects in new born
Introduction: Tobacco-smoking is one of the most important risk factor for preterm delivery, pregnancy loss, low birth weight, and fetal growth restriction. It is estimated that approximately 30% of growth-restricted neonates could be independently associated with maternal smoking.Methods: In this study, gene expression profile, GSE11798, was chosen from GEO database with an aim to perceive change in gene expression signature in new born due to maternal smoking. Enrichment analysis was performed to annotate differentially expressed genes (DEGs) through gene ontology and pathway analysis using DAVID. Protein–protein interactions and module detection of these DEGs were carried out using cytoscape v3.6.0. Thirty umbilical cord tissue samples from 15 smokers and 15 non-smokers pregnant women were included in this analysis.Results: Twenty-six differentially expressed genes (DEGs) between two groups were selected using GEO2R tool. The DEGs were observed to be participating in biological processes/pathways related to growth releasing hormone, angiogenesis, embryonic skeletal, and cardiac development. Fibroblast growth factor receptor-1 (FGFR1) was identified to be the hub node with 348 interacting partners, which regulates transcription, cell growth, differentiation, and apoptosis. The up-regulation of FGFR1 in umbilical cord tissue may lead to reproductive and developmental complications such as encephalocraniocutaneous lipomatosis, osteoglophonic dysplasia, and Pfeiffer syndrome in new-borns.Conclusion: The findings manifests the possibility of overcoming these adverse health effects in new born through FGFR1 modulating treatments during pregnancy.
2017-08-18 | ARQ 087 inhibits FGFR signaling and rescues aberrant cell proliferation and differentiation in experimental models of craniosynostoses and chondrodysplasias caused by activating mutations in FGFR1, FGFR2 and FGFR3
Tyrosine kinase inhibitors are being developed for therapy of malignancies caused by oncogenic FGFR signaling but little is known about their effect in congenital chondrodysplasias or craniosynostoses that associate with activating FGFR mutations. Here, we investigated the effects of novel FGFR inhibitor, ARQ 087, in experimental models of aberrant FGFR3 signaling in cartilage. In cultured chondrocytes, ARQ 087 efficiently rescued all major effects of pathological FGFR3 activation, i.e. inhibition of chondrocyte proliferation, loss of extracellular matrix and induction of premature senescence. In ex vivo tibia organ cultures, ARQ 087 restored normal growth plate architecture and eliminated the suppressing FGFR3 effect on chondrocyte hypertrophic differentiation, suggesting that it targets the FGFR3 pathway specifically, i.e. without interference with other pro-growth pathways. Moreover, ARQ 087 inhibited activity of FGFR1 and FGFR2 mutants associated with Pfeiffer, Apert and Beare-Stevenson craniosynostoses, and rescued FGFR-driven excessive osteogenic differentiation in mouse mesenchymal micromass cultures or in ex vivo calvarial organ cultures. Our data warrant further development of ARQ 087 for clinical use in skeletal disorders caused by activating FGFR mutations.
2017-05-10 | A Case of Pediatric Post-Traumatic Stress Disorder Presenting as Attention Deficit Hyperactivity Disorder: A Case Report
In the past few years, there has been increased recognition that children, who have faced traumatic incidences, can develop post-traumatic stress disorder (PTSD), just like in adults. We present a case of PTSD in a 6-year-old child who endured three surgical procedures because he was suffering from a congenital cranial stenosis (Pfeiffer) syndrome. Because of repetitive painful episodes, resulting from the syndrome, and then post-surgical complications, the child developed behavioral outbursts, hypervigilence, concentration problems, and irritability. In the past, the child was diagnosed with attention deficit hyperactivity disorder (ADHD) in the realm of his behavioral complaints, and he was already on stimulant medications for last one year. But there was no remarkable effect of pharmacotherapy on child's behavior despite increasing dosages. Ultimately the child's medical and psychiatric history was reviewed and a diagnosis of pediatric PTSD was made. Stimulant medications were discontinued and management was started on the lines of pediatric PTSD, resulting in a remarkable improvement in child's psychiatric outcome.
gene therapies
2026-04-24 | The Clinical and Molecular Spectrum of Turkish Patients with Syndromic Craniosynostosis: A Single Center Study
Objective: Syndromic craniosynostosis is caused by pathogenic variants in genes regulating suture development. This study aims to investigate clinical and molecular characteristics in syndromic craniosynostosis. Materials and Methods: This retrospective descriptive study included 53 patients from 40 families with syndromic craniosynostosis. Molecular testing was performed in 22 families. Results: The study included Saethre-Chotzen (n=14), Apert (n=12), Crouzon (n=11), Pfeiffer (n=4), Muenke (n=4), and Carpenter (n=1) syndromes, Crouzon syndrome with acanthosis nigricans (n=2), craniosynostosis with dental anomalies (n=2), craniosynostosis type 4 (n=2), and hypochondroplasia with craniosynostosis (n=1). Genetic etiology was identified in 20 families involving six genes: FGFR1 (Pfeiffer), FGFR2 (Apert, Crouzon, Pfeiffer), FGFR3 (Crouzon with acanthosis nigricans, Muenke), TWIST1 (Saethre-Chotzen), ERF (Craniosynostosis type 4), and IL11RA (Craniosynostosis with dental anomaly). Additionally, a FGFR3 variant causing hypochondroplasia was identified in a patient with multisuture synostosis. Familial inheritance was identified in 25%, but not in Apert syndrome. Brachycephaly (28.3%) was the most common cranial abnormality, followed by plagiocephaly (22.6%). Apert syndrome was characterized by frequent cardiac anomalies, cleft palate, developmental delay, and a higher rate of surgical intervention. In contrast, Crouzon, Pfeiffer, Saethre–Chotzen, and Muenke syndromes showed favorable outcomes, although a fatal course was observed in a patient with Crouzon syndrome with acanthosis nigricans. Rare etiologies included ERF-related craniosynostosis with mild craniofacial findings and IL11RA-related craniosynostosis with intrafamilial phenotypic heterogeneity. Conclusion: This study describes clinical features of well-defined syndromes such as Apert, Crouzon, and Pfeiffer; reports craniosynostosis in hypochondroplasia; and documents rare ERF- and IL11RA-related forms, highlighting the importance of combining clinical and molecular diagnostics.
2026-02-18 | Prenatal and Postmortem Characterization of FGFR2-Related Fetal Craniosynostosis: Emphasizing Rare and Atypical Anomalies.
Craniosynostosis (CS) is the second most common craniofacial birth defect after orofacial clefts. Genetic counseling is essential for reproductive planning in affected families. Nine fetal CS cases-six Apert syndrome (AS) and three Pfeiffer syndrome (PS)-with established genetic causes were retrospectively analyzed for clinical, radiological, and molecular features. Mean gestational age at first examination was 26.2 weeks. Four AS and two PS cases were diagnosed during the prenatal stage by ultrasonography (USG), whereas two AS and one PS cases were identified during postmortem. Common prenatal findings included polyhydramnios, high flat forehead, and syndactyly. Two of the three cases diagnosed at the postmortem stage had multiple congenital anomalies (MCA), while in the third, CS was suspected due to frontal bossing and proptosis despite the absence of classic signs. All cases carried pathogenic FGFR2 variants. Proptosis, frontal bossing, and trigonocephaly are key prenatal indicators of CS, but their absence-especially with systemic anomalies-can challenge diagnosis. In cases with MCA, CS should be suspected even if classic signs are absent, particularly when syndactyly accompanies other complex abnormalities. Postmortem evaluation and molecular genetic testing are essential for definitive diagnosis, especially when clinical features are ambiguous.
2025-05-20 | A Rare Case of Prenatally Diagnosed Pfeiffer Syndrome with Multicystic Kidney.
Pfeiffer syndrome is a rare syndromic craniosynostosis characterized by bilateral coronal craniosynostosis, midface hypoplasia, beaked nasal tip, broad and medially deviated thumbs and great toes. It is caused by mutations affecting the fibroblast growth factor receptors type 1 or 2 (FGFR1 or FGFR2), with autosomal dominant inheritance. It displays substantial clinical and genetic heterogeneity. The disorder is usually detected in the neonatal period, and very few prenatally diagnosed cases have been reported.
2023-07-31 | Molecular Scalpels: The Future of Pediatric Craniofacial Surgery?
CRISPR-Cas genome editing tools are among the most substantial advances in the life sciences in modern history. Single-dose gene therapies to correct pathogenic mutations have moved quickly from bench to bedside, with several therapeutics designed by CRISPR pioneers entering various stages of clinical investigation. Applications of these genetic technologies are poised to reshape the practice of both medicine and surgery. Many of the most morbid conditions treated by craniofacial surgeons are syndromic craniosynostoses caused by mutations in fibroblast growth factor receptor genes, including Apert, Pfeiffer, Crouzon, and Muenke syndromes. The fact that pathogenic mutations in these genes are recurrent in the majority of affected families presents a unique opportunity to develop "off-the-shelf" gene editing therapies to correct these mutations in affected children. The therapeutic potential of these interventions could reshape pediatric craniofacial surgery, potentially first eliminating the need for midface advancement procedures in affected children.
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