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Pediatric Annals Feb 2020Benign congenital anomalies are common in neonates. Some of these common benign congenital anomalies include preauricular pits, sacral dimples, supernumerary digits,... (Review)
Review
Benign congenital anomalies are common in neonates. Some of these common benign congenital anomalies include preauricular pits, sacral dimples, supernumerary digits, accessory nipple, and natal teeth. It is important for health care providers who take care of newborns to recognize these benign anomalies so that unnecessary evaluations and investigations are not performed. However, some of these anomalies may be associated with clinically significant conditions. In this article, we discuss when further evaluation should be performed in babies presenting with these common benign congenital anomalies. [Pediatr Ann. 2020;49(2):e66-e70.].
Topics: Congenital Abnormalities; Humans; Infant, Newborn
PubMed: 32045484
DOI: 10.3928/19382359-20200121-03 -
Genetics in Medicine : Official Journal... Nov 2022Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is characterized by congenital absence of the uterus, cervix, and the upper part of the vagina in females. Whole-gene...
PURPOSE
Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is characterized by congenital absence of the uterus, cervix, and the upper part of the vagina in females. Whole-gene deletion and loss-of-function variants in TBX6 have been identified in association with MRKHS. We aimed to expand the spectrum of TBX6 variants in MRKHS and explore the biological effect of the variant alleles.
METHODS
Rare variants in TBX6 were called from a combined multiethnic cohort of 622 probands with MRKHS who underwent exome sequencing or genome sequencing. Multiple in vitro functional experiments were performed, including messenger RNA analysis, western blotting, transcriptional activity assay, and immunofluorescence staining.
RESULTS
We identified 16 rare variants in TBX6 from the combined cohort, including 1 protein-truncating variant reported in our previous study and 15 variants with unknown effects. By comparing the prevalence of TBX6 variants in the Chinese MRKHS cohort vs 1038 female controls, we observed a significant mutational burden of TBX6 in affected individuals (P = .0004, odds ratio = 5.25), suggesting a causal role of TBX6 variants in MRKHS. Of the 15 variants with uncertain effects, 7 were shown to induce a loss-of-function effect through various mechanisms. The c.423G>A (p.Leu141=) and c.839+5G>A variants impaired the normal splicing of TBX6 messenger RNA, c.422T>C (p.Leu141Pro) and c.745G>A (p.Val249Met) led to decreased protein expression, c.10C>T (p.Pro4Ser) and c.400G>A (p.Glu134Lys) resulted in perturbed transcriptional activity, and c.356G>A (p.Arg119His) caused protein mislocalization. We observed incomplete penetrance and variable expressivity in families carrying deleterious variants, which indicates a more complex genetic mechanism than classical Mendelian inheritance.
CONCLUSION
Our study expands the mutational spectrum of TBX6 in MRKHS and delineates the molecular pathogenesis of TBX6 variants, supporting the association between deleterious variants in TBX6 and MRKHS.
Topics: Female; Humans; 46, XX Disorders of Sex Development; Mullerian Ducts; Vagina; RNA, Messenger; Congenital Abnormalities; T-Box Domain Proteins
PubMed: 36112137
DOI: 10.1016/j.gim.2022.08.012 -
Epidemiologia E Prevenzione 2020
Topics: Congenital Abnormalities; Humans; Italy
PubMed: 32374101
DOI: 10.19191/EP20.1.P004.005 -
American Journal of Medical Genetics.... May 2021Trisomy 13 is one of the three most common aneuploidy syndromes in live-born infants. It is associated with mortality rates as high as 90% within the first year of life,... (Review)
Review
Trisomy 13 is one of the three most common aneuploidy syndromes in live-born infants. It is associated with mortality rates as high as 90% within the first year of life, in large part, due to the high prevalence of severe congenital abnormalities that increase mortality and morbidity. However, life-saving and life-prolonging medical interventions are being performed at a higher rate for these infants, resulting in increased rates of survival. Although cardiac complications have been well described in infants with trisomy 13, these patients also experience other complications such as respiratory, neurological, genitourinary, abdominal, otolaryngologic, and orthopedic complications that can impact their quality of life. The goal of this review is to present a comprehensive description of complications in children with trisomy 13 to aid in the development of monitoring and treatment guidelines for the increasing number of providers who will be caring for these patients throughout their lives. Where the evidence is available, this review presents screening recommendations to allow for more rapid detection and documentation of these complications.
Topics: Aneuploidy; Congenital Abnormalities; Early Medical Intervention; Female; Guidelines as Topic; Humans; Infant, Newborn; Male; Trisomy 13 Syndrome
PubMed: 33709620
DOI: 10.1002/ajmg.a.62133 -
Journal of Plastic, Reconstructive &... Feb 2021Cryptotia is characterized by an absence of the upper part of the temporoauricular sulcus with the superior third of the auricle buried under the temporal skin. The... (Clinical Trial)
Clinical Trial
INTRODUCTION
Cryptotia is characterized by an absence of the upper part of the temporoauricular sulcus with the superior third of the auricle buried under the temporal skin. The principle of correction of cryptotia is to achieve both a functional and aesthetic ear.
METHODOLOGY
A 4-year prospective study was carried out in a single centre on infants with cryptotia. We introduce a two-staged approach for non-surgical correction of cryptotia and a treatment algorithm based on the age of the patient. In the first stage, we unbury the auricle over 2 weeks. The second stage involves 2 additional weeks of helical moulding to correct the underlying or residual deformation. In our algorithm, patients more than 6 weeks of age undergo only the first stage of cryptotia correction, whereas those less than 6 weeks of age progress to the second stage of treatment.
RESULTS
A total of 5 patients (7 ears) were treated with ages ranging from 1 day to 7 months. Two patients underwent 2-stage treatment and 3 underwent 1-stage treatment. At 1 year, all buried helices remained retracted. Four out of 7 ears treated had "Excellent" outcomes and 3 out of 7 ears had "Good" outcomes. All caregivers were extremely satisfied with the outcomes.
CONCLUSION
This simple and efficacious two-stage technique and algorithm is effective in the correction of cryptotia, even if the treatment is initiated beyond the traditional moulding window in the first six weeks of life. Using this approach, patients with cryptotia benefit by avoiding or simplifying surgical reconstruction in the future.
Topics: Algorithms; Clinical Decision-Making; Congenital Abnormalities; Ear Cartilage; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Male; Prospective Studies; Traction; Treatment Outcome
PubMed: 33071167
DOI: 10.1016/j.bjps.2020.08.133 -
American Journal of Medical Genetics.... Dec 2021Robinow syndrome, a rare genetic disorder, is characterized by skeletal dysplasia with, among other anomalies, extremity and hand anomalies. There is locus heterogeneity...
Robinow syndrome, a rare genetic disorder, is characterized by skeletal dysplasia with, among other anomalies, extremity and hand anomalies. There is locus heterogeneity and both dominant and recessive inheritance. A detailed description of associated extremity and hand anomalies does not currently exist due to the rarity of this syndrome. This study seeks to document the hand anomalies present in Robinow syndrome to allow for improved rates of timely and accurate diagnosis. A focused assessment of the extremities and stature was performed using clinical examination and standard photographic images. A total of 13 patients with clinical and molecular diagnosis consistent with dominant Robinow syndrome or recessive Robinow syndrome were evaluated. All patients had limb shortening, the most common of which was mesomelia; however, rhizomelia and micromelia were also seen. These findings are relevant to clinical characterization, particularly as Robinow syndrome has classically been defined as a "mesomelic disorder." A total of eight distinct hand anomalies were identified in 12 patients with both autosomal recessive and dominant forms of Robinow syndrome. One patient did not present with any hand differences. The most common hand findings included brachydactyly, broad thumbs, and clinodactyly. A thorough understanding of the breadth of Robinow syndrome-associated extremity and hand anomalies can aid in early patient identification, improving rates of timely diagnosis and allowing for proactive management of sequelae.
Topics: Abnormalities, Multiple; Adolescent; Child; Child, Preschool; Craniofacial Abnormalities; Dwarfism; Extremities; Female; Hand; Hand Deformities, Congenital; Humans; Limb Deformities, Congenital; Male; Phenotype; Urogenital Abnormalities; Young Adult
PubMed: 32974972
DOI: 10.1002/ajmg.a.61884 -
Journal of Integrative Neuroscience Jun 2022Craniosynostosis is a rare congenital disease of the skull. They arise when one or more cranial sutures ossify prematurely. This causes an obstruction to normal brain...
BACKGROUND
Craniosynostosis is a rare congenital disease of the skull. They arise when one or more cranial sutures ossify prematurely. This causes an obstruction to normal brain growth and leads to specific deformations of the skull, which may result in intracranial hypertension and cognitive delay.
MATERIALS AND METHODS
We have retrospectively analysed all children treated at the Unit of paediatric neurosurgery of the University Medical Centre Ljubljana between June 2015 and September 2020. The following items have been recorded: affected suture, underlying syndromic condition, hydrocephalus, Chiari malformation, raised intracranial pressure, age at surgery, surgical technique, need for multiple operations and surgical complications.
RESULTS
During the study period, 71 children have been treated for craniosynostosis. The median postoperative follow-up was 31 months. There were: 54.9% sagittal, 25.3% metopic, 14.0% unicoronal, 1.4% bicoronal and 1.4% unilateral lambdoid craniosynostosis. Multiple sutures were affected in 2.8% cases. 7.0% of the cases were syndromic. Overall, 74 surgical procedures have been performed: frontoorbital advancement represented 40.5% of them; biparietal remodelling 32.4%: total cranial vault remodelling 22.9%; posterior distraction 2.7%; posterior expansion 1.3%. Median age at surgery was 12.8 months.
CONCLUSIONS
The treatment of craniosynostosis is surgical and requires a multidisciplinary approach, with expertise in plastic and reconstructive surgery, maxillofacial surgery and neurosurgery. The aim of surgical treatment is to release the constrictive and deformative effect that the synostosis has on skull growth. This requires a remodelling of the neurocranium and, if necessary, of the viscerocranium. Beyond aesthetic purposes, the primary aim of surgical treatment is to permit a normal development of the brain.
Topics: Child; Cranial Sutures; Craniosynostoses; Humans; Plastic Surgery Procedures; Retrospective Studies; Skull
PubMed: 35864758
DOI: 10.31083/j.jin2104106 -
Anales de Pediatria Feb 2020
Topics: Congenital Abnormalities; Female; Humans; Infant; Kidney; Thorax
PubMed: 30773405
DOI: 10.1016/j.anpedi.2019.01.005 -
Medical Archives (Sarajevo, Bosnia and... Aug 2022Focal dermal hypoplasia is a genetic disease of multiple systems initially affecting the skin, skeleton, dental, eyes and face with developmental abnormalities and...
BACKGROUND
Focal dermal hypoplasia is a genetic disease of multiple systems initially affecting the skin, skeleton, dental, eyes and face with developmental abnormalities and facial dysmorphism. Focal dermal hypoplasia is X-linked dominant disease affecting the ectoderm, mesoderm and endoderm. 95% feature de novo and 90% of these are females. Focal dermal hypoplasia is induced by a mutation in the PORCN gene.
OBJECTIVE
The aim of this article is to present a case of a one-year-old girl child with multi-hypopigmented reticulated atrophic macules and patches grouped in linear mode at the lines of blaschko, skeleton abnormalities, umbilical hernia, developmental delay, hypoplastic nails, syndactyly and lobster claw deformity.
CASE REPORT
A one-year-old girl child presented to the dermatology clinic with asymptomatic lesions since childhood with no improvement, with multi- hypopigmented skin lesions on the trunk and extremities since birth as linear erosions that heal gradually during few days, leaving peripheral hypopigmentation with hyperpigmentation with anomalies of limbs and nails and delayed development. She was born by normal vaginal delivery and weighed 2.5 kg at birth. None of the family members had such features. She had dental enamel anomaly and partial anodontia in the lower jaw. Sparse hair and partial alopecia (scalp, eyebrows and eyelashes) were recorded.
CONCLUSION
Focal dermal hypoplasia is a congenital skin disease with a unique clinical feature. Thorough examination of the extremities is indicated for early proper genetic counseling and therapy.
Topics: Female; Humans; Infant; Acyltransferases; Focal Dermal Hypoplasia; Limb Deformities, Congenital; Membrane Proteins; Mutation; Skin
PubMed: 36313953
DOI: 10.5455/medarh.2022.76.301-304 -
American Journal of Medical Genetics.... Dec 2021Robinow syndrome is characterized by mesomelic limb shortening, hemivertebrae, and genital hypoplasia. Due to low prevalence and considerable phenotypic variability, it...
Robinow syndrome is characterized by mesomelic limb shortening, hemivertebrae, and genital hypoplasia. Due to low prevalence and considerable phenotypic variability, it has been challenging to definitively characterize features of Robinow syndrome. While craniofacial abnormalities associated with Robinow syndrome have been broadly described, there is a lack of detailed descriptions of genotype-specific phenotypic craniofacial features. Patients with Robinow syndrome were invited for a multidisciplinary evaluation conducted by specialist physicians at our institution. A focused assessment of the craniofacial manifestations was performed by a single expert examiner using clinical examination and standard photographic images. A total of 13 patients with clinical and molecular diagnoses consistent with either dominant Robinow syndrome (DRS) or recessive Robinow syndrome (RRS) were evaluated. On craniofacial examination, gingival hyperplasia was nearly ubiquitous in all patients. Orbital hypertelorism, a short nose with anteverted and flared nares, a triangular mouth with a long philtrum, cleft palate, macrocephaly, and frontal bossing were not observed in all individuals but affected individuals with both DRS and RRS. Other anomalies were more selective in their distribution in this patient cohort. We present a comprehensive analysis of the craniofacial findings in patients with Robinow Syndrome, describing associated morphological features and correlating phenotypic manifestations to underlying genotype in a manner relevant for early recognition and focused evaluation of these patients.
Topics: Abnormalities, Multiple; Adolescent; Adult; Child; Child, Preschool; Craniofacial Abnormalities; Dwarfism; Female; Genes, Dominant; Genes, Recessive; Genotype; Humans; Hypertelorism; Limb Deformities, Congenital; Male; Middle Aged; Mouth Abnormalities; Mutation; Phenotype; Spine; Urogenital Abnormalities; Young Adult
PubMed: 33237614
DOI: 10.1002/ajmg.a.61986