Prenatal diagnosis of Apert syndrome

2018 ◽  
Author(s):  
N.P. Veropotvelyan , D.I. Laylo , T.V. Usenko
Keyword(s):  
Prenatal Diagnosis ◽  
Autosomal Dominant ◽  
De Novo ◽  
The Other ◽  
Lower Limbs ◽  
Apert Syndrome ◽  
Type I ◽  
Autosomal Dominant Disorder ◽  
Nasal Bridge ◽  
Skull Shape

Apert syndrome is a rare monogenic autosomal dominant disorder characterized by severe craniosynostosis, hypoplastic mediofacial structures and symmetric syndactyly of the upper and lower limbs. De novo case with Apert synclrome fetus was detected prenatally at 19–20 weeks of gestation when echography showed next pathognomic signs: an abnormal skull shape, frontal bossing, mild pachygyria, severe hypertelorism bilateral exophthalmos, deep nasal bridge, short upturned nose, prognathia, long filtrum, mild microgenia and ful syndactyly of the feet and hands. Differential diagnosis with other acrocephalosyndactyly types was performed. It is considered, that this is the earliest term of this syndrom prenatal diagnosis in a low risk pregnancies with unimpaired family history. By the parents desire this pregnancy was terminated and subsequent autopsy confirmed the diagnosis of Apert syndrome (acrocephalosyndactyly — type I) one of the hands looks like mitten the other one has the bucket shape.

scholarly journals Apert Syndrome in the Era of Prenatal Diagnosis

2014 ◽  
Vol 8 (2) ◽  
pp. 222-225
Author(s):  
Florin Stamatian ◽  
Gabriela Caracostea ◽  
Tunde Kovacs ◽  
Mariela Militaru
Keyword(s):  
Prenatal Diagnosis ◽  
Dna Analysis ◽  
Heart Defects ◽  
Restriction Enzymes ◽  
Lower Limbs ◽  
Apert Syndrome ◽  
Second Trimester ◽  
Autosomal Dominant Disorder ◽  
Fetal Dna ◽  
Cell Free Fetal Dna

ABSTRACT Apert syndrome is a rare autosomal dominant disorder characterized by severe craniosynostosis, hypoplastic mediofacial structures and symmetric syndactyly. The syndactyly involves both cutaneous and osseous structures of the upper and lower limbs. Apart from skeletal anomalies, affected fetuses may often present central nervous system malformations and various visceral malformations (congenital heart defects, genitourinary anomalies, choanal stenosis, tracheal abnormalities, diaphragmatic hernia and omphalocele). Mental retardation is frequently encountered, as are a large variety of craniofacial and neurocognitive phenotypes. The incidence of Apert syndrome is approximately one in 65,000 newborns, representing 4.5% of all craniosynostosis cases. The first cases of Apert syndrome were diagnosed by ultrasound and fetoscopy in the third trimester of pregnancy. With the introduction of three-dimensional (3D) ultrasonography, identification of fetal changes characteristic of Apert syndrome is possible in the second trimester of pregnancy. Diagnosis confirmation requires fetal DNA analysis by fibroblast growth factor receptor 2 gene amplification (FGFR2) followed by sequencing and digestion with restriction enzymes. Recently, noninvasive prenatal diagnosis was reported using free fetal DNA analysis with cell-free fetal DNA (cffDNA) in maternal plasma by Polymerase Chain Reaction (PCR) assay and enzymatic digestion with restriction enzymes. As the syndrome has rarely been reported in Romania, we present the case of a fetus diagnosed with Apert syndrome in the second trimester of pregnancy. Early ultrasound detection of suggestive signs for this syndrome (craniosynostosis, syndactyly) was followed by confirmation of the diagnosis by prenatal fetal DNA analysis. How to cite this article Stamatian F, Kovacs T, Militaru M, Caracostea G. Apert Syndrome in the Era of Prenatal Diagnosis. Donald School J Ultrasound Obstet Gynecol 2014;8(2):222-225.

scholarly journals Tripod-shaped Syndactyly in Apert Syndrome with FGFR2 p.P253R Mutation

2021 ◽  
Author(s):  
Chandra Bhan Singh ◽  
Biswajit Mishra ◽  
Rashmi Patel ◽  
Ashok Kumar ◽  
Akhtar Ali
Keyword(s):  
Autosomal Dominant ◽  
Growth Factor Receptor ◽  
Sporadic Case ◽  
Apert Syndrome ◽  
Nasal Bridge ◽  
Craniofacial Dysmorphism ◽  
Fgfr2 Gene ◽  
Craniofacial Features ◽  
Ocular Hypertelorism ◽  
Hands And Feet

AbstractApert syndrome is a rare acrocephalosyndactyly (craniosynostosis) syndrome characterized by craniofacial dysmorphism and syndactyly of the hands and feet. It is caused by FGFR2 mutations and inherited in an autosomal dominant manner. This article describes a novel clinical variant of Apert syndrome having bilateral symmetrical tripod-shaped syndactyly in hands with milder craniofacial features in a sporadic case, along with a mutation in the fibroblast growth factor receptor 2 (FGFR2) gene. The patient had shown craniosynostosis, dysmorphic face, ocular hypertelorism, marked depression of the nasal bridge, long philtrum, and low set ears. Direct resequencing of the FGFR2 gene through Sanger’s method identified a heterozygous missense mutation; FGFR2c.758C>G (FGFR2p.P253R) in the exon-7 of the gene.

scholarly journals An Infant with Apert Syndrome and Tetralogy of Fallot for Craniosynostosis Correction: Anesthetic Challenges

2019 ◽  
Author(s):  
Karen R. Lionel ◽  
Satish K. Sundararajan ◽  
Ranjith K. Moorthy ◽  
Ramamani Mariappan
Keyword(s):  
Tetralogy Of Fallot ◽  
Autosomal Dominant ◽  
Air Embolism ◽  
Massive Bleeding ◽  
Apert Syndrome ◽  
Craniofacial Anomalies ◽  
Autosomal Dominant Disorder ◽  
Venous Air Embolism ◽  
Congenital Cardiac Anomalies ◽  
Hands And Feet

AbstractApert syndrome (AS) is an autosomal dominant disorder characterized by craniosynostosis, craniofacial anomalies, and symmetrical syndactyly of hands and feet. Ten percent children with AS can have associated congenital cardiac anomalies. Association of complex cyanotic heart disease with craniosynostosis is very rare. So far, only one case has been reported in the literature. The craniosynostosis corrective surgery is associated with the risk of massive bleeding or venous air embolism, which can cause paradoxical air embolism and precipitate cyanotic spell, which makes the anesthesia more challenging. In this report, we present the anesthetic challenges of an 8-month-old infant with AS and tetralogy of Fallot for craniosynostosis correction.

scholarly journals Identification of the molecular defect in the erythrocyte membrane skeleton of some kindreds with hereditary spherocytosis

Blood ◽  
1982 ◽  
Vol 60 (3) ◽  
pp. 772-784 ◽  
Author(s):  
SR Goodman ◽  
KA Shiffer ◽  
LA Casoria ◽  
ME Eyster
Keyword(s):  
Autosomal Dominant ◽  
Hereditary Spherocytosis ◽  
Membrane Skeleton ◽  
Molecular Defect ◽  
Type I ◽  
Autosomal Dominant Disorder ◽  
Molecular Alteration ◽  
Protein 4.1 ◽  
Disorder Type ◽  
Erythrocyte Age

Abstract We have localized the molecular alteration in the membrane skeleton of two of four kindreds with hereditary spherocytosis (HS) to an alteration in the spectrin-protein-4.1 interaction due to a defective spectrin molecule. The defective spectrin-protein-4.1 interaction in these kindreds (referred to as type I HS) leads to a weakened spectrin- protein-4.1-actin ternary complex, which in turn may lead to the friable membrane skeleton and suggested membrane instability related to this disorder. Type I HS spectrin binds approximately 63% as much protein-4.1 as normal spectrin (with equal affinity). This defect does not correlate with splenic function or erythrocyte age in the circulation. However, the approximately 37% reduction in binding of protein-4.1 to HS spectrin approaches the theoretical value of 50% expected in this autosomal dominant disorder. All other type I membrane skeletal interactions (spectrin-syndein, spectrin heterodimer- heterodimer, syndein-band-3) were found to be normal. It would appear therefore that the defective HS spectrin-protein-4.1 interaction in type I hereditary spherocytosis may be the primary molecular defect rather than a secondary phenomena.

scholarly journals A de novo STUB1 variant associated with an early adult-onset multisystemic ataxia phenotype

2021 ◽  
Author(s):  
David Mengel ◽  
Andreas Traschütz ◽  
Selina Reich ◽  
Alejandra Leyva-Gutiérrez ◽  
Friedemann Bender ◽  
...  
Keyword(s):  
Early Onset ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
De Novo ◽  
Family Members ◽  
Start Codon ◽  
Mrna Levels ◽  
Adult Onset ◽  
Loss Of Function ◽  
Autosomal Dominant Disorder

Abstract Background Biallelic STUB1 variants are a well-established cause of autosomal-recessive early-onset multisystemic ataxia (SCAR16). Evidence for STUB1 variants causing autosomal-dominant ataxia (SCA48) so far largely relies on segregation data in larger families. Presenting the first de novo occurrence of a heterozygous STUB1 variant, we here present additional qualitative evidence for STUB1-disease as an autosomal-dominant disorder. Methods Whole exome sequencing on an index patient with sporadic early-onset ataxia, followed by Sanger sequencing in all family members, was used to identify causative variants as well as to rule out alternative genetic hits and intronic STUB1 variants. STUB1 mRNA and protein levels in PBMCs in all family members were analysed using qRT-PCR and Western Blot. Results A previously unreported start-lost loss-of-function variant c.3G>A in the start codon of STUB1 was identified in the index case, occurring de novo and without evidence for a second (potentially missed) variant (e.g., intronic or copy number) in STUB1. The patient showed an early adult-onset multisystemic ataxia complicated by spastic gait disorder, distal myoclonus and cognitive dysfunction, thus closely mirroring the systems affected in autosomal-recessive STUB1-associated disease. In line with the predicted start-lost effect of the variant, functional investigations demonstrated markedly reduced STUB1 protein expression in PBMCs, whereas mRNA levels were intact. Conclusion De novo occurrence of the loss-of-function STUB1 variant in our case with multisystemic ataxia provides a qualitatively additional line of evidence for STUB1-disease as an autosomal-dominant disorder, in which the same neurological systems are affected as in its autosomal-recessive counterpart. Moreover, this finding adds support for loss-of-function as a mechanism underlying autosomal-dominant STUB1-disease, thus mirroring its autosomal-recessive counterpart also in terms of the underlying mutational mechanism.

scholarly journals Prenatal Sonographic and Molecular Genetic Diagnosis of Popliteal Pterygium Syndrome

Diagnostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1819
Author(s):  
Kuntharee Traisrisilp ◽  
Suchaya Luewan ◽  
Sirinart Sirilert ◽  
Phudit Jatavan ◽  
Theera Tongsong
Keyword(s):  
Cleft Lip ◽  
De Novo ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Ambiguous Genitalia ◽  
Knee Extension ◽  
Lower Limbs ◽  
Autosomal Dominant Disorder ◽  
Popliteal Pterygium Syndrome ◽  
Popliteal Pterygium

Popliteal pterygium syndrome (PPS) is an extremely rare autosomal dominant disorder, characterized by the cleft palate with or without cleft lip, limbs abnormalities with highly characteristic features of popliteal webbing, syndactyly, and genital abnormalities and nail anomalies. Prenatal diagnosis of PPS has been extremely rare. We describe a unique case of fetal PPS at 20 weeks of gestation. The diagnosis of PPS was based on the ultrasound findings of bilateral popliteal webbings, extending from posterior aspects of the upper thighs through the lower legs, resulting in restriction in knee extension, bilateral equinovarus feet with syndactyly, ambiguous genitalia and the grooved lip. Anatomical structures were otherwise normal. Trio whole-exome sequencing revealed a de novo heterozygous IRF6 gene mutation in the fetus, confirming the diagnosis with PPS. In conclusion, popliteal webbing or combination of facial cleft or cleft variants and bilateral abnormal postures of the lower limbs is suggestive of PPS and genetic diagnosis should be warranted.

scholarly journals A Japanese Patient with Genitopatellar Syndrome Transiently Presenting with Cardiac Intramural Cavity during the Neonatal Period

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Kiichi Takahashi ◽  
Hiroyuki Adachi ◽  
Manatomo Toyono ◽  
Masato Ito ◽  
Akie Kato ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
De Novo ◽  
Heart Defects ◽  
Ductus Arteriosus ◽  
Renal Cysts ◽  
Ventricular Septal Defects ◽  
Autosomal Dominant Disorder ◽  
Septal Defects ◽  
Pathogenic Variants

Genitopatellar syndrome (GPS) is a rare autosomal dominant disorder caused by de novo pathogenic variants in the KAT6B gene. It is characterized by genital abnormalities, patellar hypoplasia/agenesis, flexion contractures of the hips and knees, corpus callosum agenesis with microcephaly, and hydronephrosis and/or multiple renal cysts. More than half of patients with GPS have congenital heart defects, mostly atrial and/or ventricular septal defects, patent foramen ovale, and patent ductus arteriosus. We report a case of a Japanese neonate with a de novo heterozygous c.3769_3772delTCTA pathogenic variant in the KAT6B gene who presented with a cardiac intramural cavity of the ventricular septum at birth. The cavity unexpectedly disappeared at 1 month of age, but trabecular septal thinning and flash remained. The features of the cavity were not consistent with those of congenital ventricular diverticulum or aneurysm, and its identity and prognosis are still unclear. Because patients with GPS may exhibit various forms of cardiac malformation, careful cardiac examination and follow-up are required from birth in cases of suspected GPS.

scholarly journals Schinzel-Giedion Syndrome with Congenital Megacalycosis in a Turkish Patient: Report of SETBP1 Mutation and Literature Review of the Clinical Features

2017 ◽  
Vol 2017 ◽  
pp. 1-4
Author(s):  
Ozgul Bulut ◽  
Zeynep Ince ◽  
Umut Altunoglu ◽  
Sukran Yildirim ◽  
Asuman Coban
Keyword(s):  
Literature Review ◽  
Autosomal Dominant ◽  
De Novo ◽  
Facial Dysmorphism ◽  
Multiple Congenital Anomalies ◽  
Patient Report ◽  
Autosomal Dominant Disorder ◽  
Turkish Patient ◽  
Increased Risk ◽  
Risk Of Malignancy

Schinzel-Giedion syndrome (SGS) is a rare autosomal dominant disorder that results in facial dysmorphism, multiple congenital anomalies, and an increased risk of malignancy. Recently, using exome sequencing, de novo heterozygous mutations in the SETBP1 gene have been identified in patients with SGS. Most affected individuals do not survive after childhood because of the severity of this disorder. Here, we report SETBP1 mutation confirmed by molecular analysis in a case of SGS with congenital megacalycosis.

scholarly journals Apert syndrom: a literature review and own clinical case

2020 ◽  
pp. 55-58
Author(s):  
V.M. Husiev ◽  
◽  
D.S. Khapchenkova ◽  
V.E. Kleban ◽  
◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Clinical Case ◽  
Clinical Symptoms ◽  
Proximal Phalanx ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Apert Syndrome ◽  
Type I ◽  
Hands And Feet ◽  
Type V

Acrocephalosyndactyly (ACS) is a group of multiple malformations, the main clinical manifestations of which are acrocephaly and syndactyly. The most common forms are Apert (type I), Pfeiffer (type V), Setra–Hotzen (type II) syndromes. Apert syndrome is the most explored and common form of all types of ACS and Apert syndrome is estimated to occur in 1 in: 100 000 newborns. The syndrome is inherited in an autosomal dominant manner. If the gene is carried by one of the parents, the risk of having a child with Apert syndrome is 50%. The syndrome genome (FGFR2) is located on the long arm of chromosome 10 at locus 10q26. Apert syndrome occurs due to mutations at this locus, but the children karyotype is not changed. The pathognomonic clinical signs of Apert syndrome are craniofacial dysostosis and symmetrical syndactyly of the hands and feet. Acrocephaly («tower skull») — is a consequence of early synostosis of some sutures of the skull. Orbital hypertelorism and exophthalmos are referred to typical facial changes. Among other abnormalities there are heart and vascular defects (25%), cleft palate, malformations of the gastrointestinal tract and kidneys. The diagnosis is made on the basis of clinical symptoms. No treatment has been developed. Life expectancy is short. Purpose — to present a clinical case of a newborn with Apert syndrome. Clinical case. Apert syndrome was suspected prenatally, confirmed after birth. The newborn girl had the characteristic signs of the above-described pathology: «tower head», hypertelorism, saddle bridge of the nose, closed large fontanelle, phalanges of the first finger were wide, the proximal phalanx was triangular, complete cutaneous syndactyly of the II–IV fingers was observed symmetrical on both upper extremities; on the lower extremities — thickening of the proximal phalanges of the big toes, complete cutaneous syndactyly of the II–IV toes. Conclusions. The article describes a clinical case of a child with Apert syndrome. Prenatal diagnosis takes one of the leading places in confirming genetic abnormalities, determining the prognosis for life. Genetic counseling for parents is necessary and important at all stages of pregnancy planning. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of these Institutes. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: Apert syndrome, children, prenatal diagnosis.

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