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Klinische Padiatrie Mar 2024Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive multisystem disease. The pathophysiological origin is a dysfunction of the primary cilium. Clinical symptoms...
Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive multisystem disease. The pathophysiological origin is a dysfunction of the primary cilium. Clinical symptoms are heterogeneous and variable: retinal dystrophy, obesity, polydactyly, kidney abnormalities, hypogenitalism and developmental delays are the most common features. By the approval of the melanocortin 4 receptor agonist setmelanotide, a drug therapy for BBS-associated hyperphagia and obesity can be offered for the first time. Hyperphagia and severe obesity represent a considerable burden and are associated with comorbidity and increased mortality risk. Due to the limited experience with setmelanotide in BBS, a viable comprehensive therapy concept is to be presented. Therapy decision and management should be conducted in expert centers. For best therapeutic effects with setmelanotide adequate information of the patient about the modalities of the therapy (daily subcutaneous injection) and possible adverse drug events are necessary. Furthermore, the involvement of psychologists, nutritionists and nursing services (support for the application) should be considered together with the patient. The assessment of therapy response should be carried out with suitable outcome measurements and centrally reported to an adequate register.
PubMed: 38458231
DOI: 10.1055/a-2251-5382 -
Cureus Jan 2024In this report, we present the combination of on-top plasty with a modified Bilhaut-Cloquet procedure for treating atypical radial polydactyly with duplication at the...
In this report, we present the combination of on-top plasty with a modified Bilhaut-Cloquet procedure for treating atypical radial polydactyly with duplication at the metacarpophalangeal (MP) joint and triphalangism of the radial and ulnar phalanges, hypoplastic middle phalanx of the radial thumb, and hypoplastic phalanx base of the ulnar thumb. To preserve the stable MP and interphalangeal joints of the radial and ulnar thumbs, respectively, on-top plasty involved osteotomizing the middle phalanx and transferring the distal end of the middle phalanx of the ulnar finger to the phalanx base of the radial thumb. A modified Bilhaut-Cloquet procedure was used to combine the tips and nails of both thumbs. Twelve months postoperatively, good joint alignment and thumb tip appearance were achieved. On-top plasties effectively combined the desirable parts of both thumbs. The modified Bilhaut-Cloquet technique is particularly well-suited for atypical cases, such as the present case.
PubMed: 38435922
DOI: 10.7759/cureus.53285 -
Cureus Jan 2024Weyers acrofacial dysostosis (WAD) is a rare skeletal dysplasia, which is autosomal-dominant, and the clinical symptoms are presented as dental anomalies, polydactyly,...
Weyers acrofacial dysostosis (WAD) is a rare skeletal dysplasia, which is autosomal-dominant, and the clinical symptoms are presented as dental anomalies, polydactyly, nail dystrophy, and short physical stature. It is also termed "Curry‑Hall syndrome" and reported to be linked to genetic mutations mapped on chromosome 4p16, the region reported being commonly associated with a similar genetic syndrome, Ellis-van Creveld (EVC) syndrome. Most individuals with EVC have congenital heart abnormalities, most often atrial septal defects, unlike WAD. In this case, a 15‑year‑old girl presented with onychodystrophy and polydactyly observed in the hands and feet, microdontia, or agenesis of teeth, which were conical in shape, with a short stature. The patient had dystrophy of nails since birth, and physical growth in terms of height did not match the normal growth parameters with respect to age. The patient also had abnormal dentation with conical-shaped teeth, with the rest of the clinical presentations suggestive of WAD.
PubMed: 38420083
DOI: 10.7759/cureus.53135 -
JPMA. the Journal of the Pakistan... Feb 2024Ellis-van Creveld syndrome (EVC), also known as chondroectodermal dysplasia, is a rare entity. It most commonly affects the tubular bones leading to dwarfism and a long...
Ellis-van Creveld syndrome (EVC), also known as chondroectodermal dysplasia, is a rare entity. It most commonly affects the tubular bones leading to dwarfism and a long trunk with ossification defects. Other presentations are wide hands and feet, dysplastic nails, thin hair, and cardiac malformations. An eight-year-old female patient presented to our tertiary care centre with complaints of short stature, abnormal dentition, and fatigue. The child's parents were first-degree relatives. On radiological imaging, it was revealed that the patient had postaxial polydactyly, short stature, and genu valgum deformity along with mild cardiomegaly. All these features were indicative of Ellis-van Creveld syndrome. EVC is a rare clinical syndrome with a distinctive clinical presentation. It requires comprehensive radiological investigations and the management is best done with a multidisciplinary approach.
Topics: Female; Child; Humans; Ellis-Van Creveld Syndrome; Polydactyly; Heart Defects, Congenital; Fingers
PubMed: 38419244
DOI: 10.47391/JPMA.7049 -
Journal of Medical Case Reports Feb 2024We present two genetic causes of polyhydramnios that were challenging to diagnose due to their rarity and complexity. In view of the severe implications, we wish to...
BACKGROUND
We present two genetic causes of polyhydramnios that were challenging to diagnose due to their rarity and complexity. In view of the severe implications, we wish to highlight these rare genetic conditions when obstetricians consider differential diagnoses of polyhydramnios in the third trimester.
CASE PRESENTATION
Patient 1 is a 34-year-old Asian woman who was diagnosed with polyhydramnios at 28 weeks' gestation. First trimester testing, fetal anomaly scan, and intrauterine infection screen were normal. Subsequent antenatal ultrasound scans revealed macroglossia, raising the suspicion for Beckwith-Wiedemann syndrome. Chromosomal microarray analysis revealed a female profile with no pathological copy number variants. The patient underwent amnioreduction twice in the pregnancy. The patient presented in preterm labor at 34 weeks' gestation but elected for an emergency caesarean section. Postnatally, the baby was noted to have a bell-shaped thorax, coat hanger ribs, hypotonia, abdominal distension, and facial dysmorphisms suggestive of Kagami-Ogata syndrome. Patient 2 is a 30-year-old Asian woman who was diagnosed with polyhydramnios at 30 weeks' gestation. She had a high-risk first trimester screen but declined invasive testing; non-invasive prenatal testing was low risk. Ultrasound examination revealed a macrosomic fetus with grade 1 echogenic bowels but no other abnormalities. Intrauterine infection screen was negative, and there was no sonographic evidence of fetal anemia. She had spontaneous rupture of membranes at 37 + 3 weeks but subsequently delivered by caesarean section in view of pathological cardiotocography. The baby was noted to have inspiratory stridor, hypotonia, low-set ears, and bilateral toe polysyndactyly. Further genetic testing revealed a female profile with a pathogenic variant of the GLI3 gene, confirming a diagnosis of Greig cephalopolysyndactyly syndrome.
CONCLUSION
These cases illustrate the importance of considering rare genetic causes of polyhydramnios in the differential diagnosis, particularly when fetal anomalies are not apparent at the 20-week structural scan. We would like to raise awareness for these rare conditions, as a high index of suspicion enables appropriate counseling, prenatal testing, and timely referral to pediatricians and geneticists. Early identification and diagnosis allow planning of perinatal care and birth in a tertiary center managed by a multidisciplinary team.
Topics: Adult; Female; Humans; Pregnancy; Cesarean Section; Fetal Diseases; Muscle Hypotonia; Polyhydramnios; Pregnancy Trimester, Third; Ultrasonography, Prenatal
PubMed: 38369506
DOI: 10.1186/s13256-024-04435-0 -
JCI Insight Feb 2024Suppressor of fused (SUFU) is widely regarded as a key negative regulator of the sonic hedgehog (SHH) morphogenic pathway and a known tumor suppressor of medulloblastoma...
Suppressor of fused (SUFU) is widely regarded as a key negative regulator of the sonic hedgehog (SHH) morphogenic pathway and a known tumor suppressor of medulloblastoma (MB). However, we report here that SUFU expression was markedly increased in 75% of specimens compiled in a tissue array comprising 49 unstratified MBs. The SUFU and GLI1 expression levels in this MB array showed strong positive correlation, which was also identified in a large public data set containing 736 MBs. We further report that increasing Sufu gene dosage in mice caused preaxial polydactyly, which was associated with the expansion of the Gli3 domain in the anterior limb bud and heightened Shh signaling responses during embryonic development. Increasing Sufu gene dosage also led to accelerated cerebellar development and, when combined with ablation of the Shh receptor encoded by Patched1 (Ptch1), promoted MB tumorigenesis. These data reveal multifaceted roles of SUFU in promoting MB tumorigenesis by enhancing SHH signaling. This revelation clarifies potentially counterintuitive clinical observation of high SUFU expression in MBs and may pave way for novel strategies to reduce or reverse MB progression.
Topics: Mice; Animals; Medulloblastoma; Repressor Proteins; Hedgehog Proteins; Cell Transformation, Neoplastic; Transcription Factors; Cerebellar Neoplasms; Polydactyly
PubMed: 38358805
DOI: 10.1172/jci.insight.176044 -
Cureus Feb 2024The dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly (DREAM-PL) syndrome is a rare autosomal recessive disorder...
Extensive Phenotypic Variability in Syndrome Dysmorphic Facies, Renal Agenesis, Ambiguous Genitalia, Microcephaly, Polydactyly, and Lissencephaly (DREAM-PL): A Case Report Highlighting Diagnostic and Management Challenges.
The dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly (DREAM-PL) syndrome is a rare autosomal recessive disorder characterized by dysmorphic facies, renal agenesis, ambiguous genitalia in males, microcephaly, polydactyly, and lissencephaly. The CTU2 gene, which encodes a protein involved in the post-transcriptional modification of tRNAs is the source of the syndrome's mutation. Several developmental abnormalities can result from a disruption of this modification, which is necessary for the proper translation of genes. The severity of the symptoms of DREAM-PL syndrome can range from moderate to severe, and its clinical characteristics are quite diverse. Some patients might have some of the distinguishing characteristics, whereas others might have all of them. The most typical characteristics include ambiguous genitalia, dysmorphic facies, and microcephaly. DREAM-PL syndrome is diagnosed based on clinical signs and genetic testing which can show mutations in the CTU2 gene. Although there is no known cure for this syndrome, the treatment aims to manage the symptoms. Other lines of treatment like surgical correction of birth defects can sometimes be beneficial to these patients in addition to supportive care. This study is a report of a 37-week-old male neonate, delivered by lower segment cesarean section. The baby's birth weight is 2.760 kg with a heterozygous confirmed pathogenic mutation of the CTU2 gene confirmed by whole-exome sequencing.
PubMed: 38348206
DOI: 10.7759/cureus.54043 -
Annals of Medicine and Surgery (2012) Feb 2024Bardet-Biedl syndrome (BBS) is a rare autosomal recessive multisystem disorder characterized by retinal dystrophy, obesity, postaxial polydactyly, renal dysfunction,...
INTRODUCTION
Bardet-Biedl syndrome (BBS) is a rare autosomal recessive multisystem disorder characterized by retinal dystrophy, obesity, postaxial polydactyly, renal dysfunction, learning difficulties, and hypogonadism. In this case report, the authors present the clinical course and management of a patient with BBS who developed chronic kidney disease (CKD).
CASE PRESENTATION
An 18-year-old male presented to the emergency department with chief complaints of fever, cough, vomiting, and decreased urine output for 7 days. Parents complained that the child had a delay in development compared to other children of the same age group. On examination, the patient had tachypnea, periorbital and pedal edema, expiratory wheeze with bilateral basal crackles, polydactyly, central obesity, microtestes, and delayed developmental milestones. Ultrasonography revealed bilateral small kidneys with increased cortical echotexture and loss of corticomedullary differentiation. Based on clinical features, the patient was diagnosed with CKD in the background of BBS. Hemodialysis was initiated after the diagnosis.
DISCUSSION
The management of CKD in the background of BBS poses unique challenges due to the complex multisystem involvement of this genetic disorder. There should be early reorganization and management of this condition so that the patient can have a better quality of life. Moreover, in developing countries like Nepal, genetic testing and diagnosis should be made easily accessible for better patient outcome.
CONCLUSION
Multidisciplinary approach involving nephrologists, ophthalmologists, endocrinologists, and geneticists is important to optimize the treatment and long-term management of Badet Biedel patients.
PubMed: 38333249
DOI: 10.1097/MS9.0000000000001626