A case-control study characterizing polydactyly risk factors in Bogotá and Cali, Colombia between 2002 and 2020.

BACKGROUND: Polydactyly is a congenital abnormality characterized by the presence of additional fingers on one or more extremities. In Colombia, polydactyly accounted for 17% of musculoskeletal congenital abnormalities in 2021, with a prevalence of 6.03 per 10,000 live births. The purpose of this study was to determine the prevalence of polydactyly and identify associated risk factors in Bogotá and Cali, Colombia, from 2002 to 2020. METHODS: A retrospective case-control study design was employed, analyzing data from birth defect reports provided by the Program for the Prevention and Follow-up of Congenital Defects and Orphan Diseases surveillance system. Cases included live births or stillbirths with polydactyly, while controls consisted of infants without congenital abnormality, matched in terms of birth date and hospital. Prevalence of polydactyly was calculated and risk factors were assessed through odds ratios obtained by logistic regression models, considering a 95% confidence interval. RESULTS: Among the 558,255 births included in the study, 848 cases of polydactyly were identified, resulting in a prevalence rate of 15.19 per 10,000 live births. Risk factors associated with polydactyly included male newborn sex, pregestational diabetes, and a family history of malformation among first-degree relatives. CONCLUSION: These findings highlight the importance a surveillance system aimed to characterize populations with congenital abnormalities, providing a better option for analyzing risk factors, help improving prevention, diagnosis, notification, and optimal treatment in patients.

Ellis-van Creveld Syndrome 2 With Novel Partial Exon 11 Deletion: A Case From Saudi Arabia.

Ellis-van Creveld syndrome (EVC) is a rare genetic disorder characterized by chondral and ectodermal dysplasia. Clinical features may include polydactyly, growth retardation, short ribs, and heart defects. The exact prevalence is still unclear; however, the Amish community in the United States is the most common community to report this rare disease. Until now, only six cases have been reported in Saudi Arabia so far. This is the first case to be reported in the Jazan region. Jazan covers an area of 11,671 km² and has a population of 1,567,547 at the 2017 census. This region has the highest population density with a high consanguinity marriage rate. We present a case of EVC with typical clinical findings, which was confirmed by homozygous mutation in the EVC2 gene in the region of Jazan, Saudi Arabia. Besides the six cases that were reported from Saudi Arabia, this makes it a total of seven cases. The prenatal findings are considered a good predictor of the disease outcome. More effort is needed in making a national registry of rare disorders to report such cases and provide more awareness among highly consanguinity marriage communities.

Overlapping holoprosencephaly-polydactyl syndrome and asphyxiating thoracic dystrophy, an incidental finding in late prenatal ultrasound: A rare case report.

Holoprosencephaly-polydactyly syndrome and asphyxiating thoracic dystrophy rarely overlap but if they do, they have poorer prognosis. Early prenatal detection of multiple congenital anomalies plays a crucial role in the management of pregnancy.

Novel mutations of TCTN3/LTBP2 with cellular function changes in congenital heart disease associated with polydactyly.

Congenital heart disease (CHD) associated with polydactyly involves various genes. We aimed to identify variations from genes related to complex CHD with polydactyly and to investigate the cellular functions related to the mutations. Blood was collected from a complex CHD case with polydactyly, and whole exome sequencing (WES) was performed. The CRISPR/Cas9 system was used to generate human pluripotent stem cell with mutations (hPSCs-Mut) that were differentiated into cardiomyocytes (hPSC-CMs-Mut) and analysed by transcriptomics on day 0, 9 and 13. Two heterozygous mutations, LTBP2 (c.2206G>A, p.Asp736Asn, RefSeq NM_000428.2) and TCTN3 (c.1268G>A, p.Gly423Glu, RefSeq NM_015631.5), were identified via WES but no TBX5 mutations were found. The stable cell lines of hPSCs-LTBP2mu /TCTN3mu were constructed and differentiated into hPSC-CMs-LTBP2mu /TCTN3mu . Compared to the wild type, LTBP2 mutation delayed the development of CMs. The TCTN3 mutation consistently presented lower rate and weaker force of the contraction of CMs. For gene expression pattern of persistent up-regulation, pathways in cardiac development and congenital heart disease were enriched in hPSCs-CM-LTBP2mu , compared with hPSCs-CM-WT. Thus, the heterozygous mutations in TCTN3 and LTBP2 affect contractility (rate and force) of cardiac myocytes and may affect the development of the heart. These findings provide new insights into the pathogenesis of complex CHD with polydactyly.

Genetic Instability of a Polydactyl Hypopigmented Cat With Squamous Cell Carcinoma-A Case Report.

Polydactyly, hypopigmentation, and squamous cell carcinoma are common in cats. However, a cat exhibiting all of these conditions has not yet been reported. This study presents the case of a 14- year-old male Mexican cat, hypopigmented, with supernumerary fingers, two preaxial and one on each posterior limb, admitted to the clinic with a lesion in the left periocular region. The cat was subjected to a general physical examination, blood, and urine chemistry, as well as a biopsy and genomic instability assessment with an analysis of the red blood cells (RBC) micronucleated erythrocytes (RBC-MNE) in the peripheral blood. The biopsy was positive for squamous cell carcinoma, and the RBC-MNE count (8.6 MNE/1000 erythrocytes) was high compared to that previously described in other domestic cats or wild cats. Thus, the genomic instability of the RBC-MNE could be used as an indicator to identify clinical conditions of felines, particularly those with one of the characteristics exhibited by this Mexican cat. The RBC-MNE test is the most widely used in the world for the evaluation of DNA damage, but to our knowledge, it has not been used to identify vulnerable non-human specimens.

Genetic heterogeneity of polydactyly in Maine Coon cats.

OBJECTIVES: Polydactyly has been described in two breeds of domestic cats (Maine Coon and Pixie Bob) and in some outbred domestic cats (eg, Hemingway cats). In most cases, feline polydactyly is a non-syndromic preaxial polydactyly. Three variants located in a regulatory sequence involved in limb development, named ZRS (zone of polarising activity regulatory sequence), have been identified to be responsible for feline polydactyly. These variants have been found in outbred domestic cats in the UK (UK1 and UK2 variants) and in Hemingway cats in the USA (Hw variant). The aim of this study was to characterise the genetic features of polydactyly in Maine Coon cats. METHODS: Genotyping assay was used to identify the variant(s) segregating in a cohort of 75 polydactyl and non-polydactyl Maine Coon cats from different breeding lines from Europe, Canada and the USA. The authors performed a segregation analysis to identify the inheritance pattern of polydactyly in this cohort and analysed the population structure. RESULTS: The Hw allele was identified in a subset of polydactyl cats. Sequencing of two regulatory sequences involved in limb development did not reveal any other variant in polydactyl cats lacking the Hw allele. Additionally, genotype-phenotype and segregation analyses revealed the peculiar inheritance pattern of polydactyly in Maine Coon cats. The population structure analysis demonstrated a genetic distinction between Hw and Hw-free polydactyl cats. CONCLUSIONS AND RELEVANCE: Polydactyly in Maine Coon cats is inherited as an autosomal dominant trait with incomplete penetrance and variable expressivity, and this trait is characterised by genetic heterogeneity in the Maine Coon breed. Maine Coon breeders should be aware of this situation and adapt their breeding practices accordingly.

Semilobar holoprosencephaly with cebocephaly associated with maternal early onset preeclampsia: a case report.

BACKGROUND: The term holoprosencephaly was proposed by DeMyer and Zeman. It is a developmental defect of the embryonic forebrain with heterogeneous etiology including genetic and environmental factors. It is commonly associated with midfacial defects and has a spectrum of presentations. There are four types: alobar, semilobar, lobar, and variant. Holoprosencephaly is relatively rare. The overall prevalence in a multicenter study was 1 in 13,000 to 18,000 live births. However, the presentation of holoprosencephaly with cebocephaly, micropenis, agenesis of middle phalanges of the fifth finger, and postaxial polydactyly in association with early onset preeclampsia is extremely rare. We report a case with a constellation of the above congenital anomalies. CASE PRESENTATION: A 34-year-old gravida II para l woman presented to Felege Hiwot Referral Hospital with the diagnosis of semilobar holoprosencephaly and early onset preeclampsia with severity features. The gestational age at admission was 26 + 3 weeks. She is Amhara by ethnicity. The pregnancy was from a non-consanguineous marriage. She presented with the complaints of severe and persistent headache associated with blurring of vision and generalized body swelling. After she was stabilized, she and her husband were counselled and termination was decided. She gave birth after three doses of 100 microgram misoprostol given vaginally every 3 hours. The outcome was 1.1 kg male neonate; there were associated dysmorphic features of holoprosencephaly such as cebocephaly, micropenis, and postaxial polydactyl with agenesis of middle phalanges of the fifth finger. Only basic care was given and the neonate died after 20 minutes' stay in our neonatal intensive care unit. The mother was counselled to have preconception and antenatal screening in her next pregnancy. She left the hospital relatively well. CONCLUSION: In women with a history of holoprosencephaly or holoprosencephaly in the current pregnancy, antenatal workups should include workup for fetal chromosomal disorders and metabolic workup for maternal preeclampsia. Sonographic diagnoses of holoprosencephaly always need a careful search for other congenital anomalies. In the severe forms, early termination should be counseled for its poor prognosis. Associated severe congenital anomalies and severe morbidities of the survivor can be discussed while counselling.

Síndrome de Ellis Van Creveld: caso clínico / Ellis Van Creveld syndrome: case report

El Síndrome de Ellis Van Creveld es poco frecuente, hereditario de carácter autosómico recesivo no habiendo predilección por sexo. Se caracteriza por acortamiento acromesomélico, polidactilia postaxial bilateral de manos, condrodisplasia de huesos largos y displasia ectodérmica de uñas y dientes. El conocimiento de la misma es imperativo para un diagnóstico temprano y manejo multidisciplinario oportuno que permita una mejor calidad de vida de estos pacientes.

The Ellis Van Creveld syndrome is rare, hereditary autosomal recessive, without no sex predilection. It is characterized by short-limbed dwarfism, bilateral postaxial hand polydactyl, chondrodysplasia of long bones and ectodermic dysplasia affecting fingernails and teeth. The knowledge of it is essential for early diagnosis and appropriate multidisciplinary management that allows a better quality of life for these patients.