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European Journal of Orthodontics Jan 2021Juberg-Hayward syndrome (JHS; MIM 216100) is a rare autosomal recessive malformation syndrome, characterized by cleft lip/palate, microcephaly, ptosis, short stature,...
BACKGROUND
Juberg-Hayward syndrome (JHS; MIM 216100) is a rare autosomal recessive malformation syndrome, characterized by cleft lip/palate, microcephaly, ptosis, short stature, hypoplasia or aplasia of thumbs, and dislocation of radial head and fusion of humerus and radius leading to elbow restriction.
OBJECTIVE
To report for the first time the molecular aetiology of JHS.
PATIENT AND METHODS
Clinical and radiographic examination, whole exome sequencing, Sanger sequencing, mutant protein model construction, and in situ hybridization of Esco2 expression in mouse embryos were performed.
RESULTS
Clinical findings of the patient consisted of repaired cleft lip/palate, microcephaly, ptosis, short stature, delayed bone age, hypoplastic fingers and thumbs, clinodactyly of the fifth fingers, and humeroradial synostosis leading to elbow restriction. Intelligence is normal. Whole exome sequencing of the whole family showed a novel homozygous base substitution c.1654C>T in ESCO2 of the proband. The sister was homozygous for the wildtype variant. Parents were heterozygous for the mutation. The mutation is predicted to cause premature stop codon p.Arg552Ter. Mutations in ESCO2, a gene involved in cohesin complex formation, are known to cause Roberts/SC phocomelia syndrome. Roberts/SC phocomelia syndrome and JHS share similar clinical findings, including autosomal recessive inheritance, short stature, cleft lip/palate, severe upper limb anomalies, and hypoplastic digits. Esco2 expression during the early development of lip, palate, eyelid, digits, upper limb, and lower limb and truncated protein model are consistent with the defect.
CONCLUSIONS
Our study showed that Roberts/SC phocomelia syndrome and JHS are allelic and distinct entities. This is the first report demonstrating that mutation in ESCO2 causes JHS, a cohesinopathy.
Topics: Acetyltransferases; Animals; Chromosomal Proteins, Non-Histone; Cleft Lip; Cleft Palate; Humans; Mice; Mutation; Orofaciodigital Syndromes
PubMed: 32255174
DOI: 10.1093/ejo/cjaa023 -
The Journal of Hand Surgery... Aug 2022Laurin-Sandrow syndrome (LSS) is an extremely rare syndrome of mirror hand and leg with less than 20 cases reported in literature. The syndrome has been attributed to a... (Review)
Review
Laurin-Sandrow syndrome (LSS) is an extremely rare syndrome of mirror hand and leg with less than 20 cases reported in literature. The syndrome has been attributed to a mutation in the MIPOL-1 (mirror-image polydactyly) gene located on locus 14q13.3-q21 coding for CCDC193 (coiled-coli domain containing 193) protein. It is characterised by limb, facial and central nervous system anomalies with the most constant being fibular dimelia with fibular ray duplication, polydactyly with secondary deformities of fixed equinus, knee joint instability and flexion deformity. It is associated less frequently with ulnar dimelia, thumb aplasia/hypoplasia, ulnar ray duplication, symbrachypolydactyly, 'rosette' hands, facial dysmorphism like hypertelorism, broad columella and flat nose, CNS anomalies like aplasia/hypoplasia of corpus callosum, hydrocephalus and muscular dystonia. We report a 2-year-old male child with LSS and perform a literature review to expound on this rare syndrome. Level V (Therapeutic).
Topics: Abnormalities, Multiple; Child; Child, Preschool; Ectromelia; Foot Deformities, Congenital; Hand Deformities, Congenital; Humans; Male; Nose; Syndrome
PubMed: 35965362
DOI: 10.1142/S2424835522720389 -
Cell Cycle (Georgetown, Tex.) Mar 2022Cornelia de Lange syndrome (CdLS) and Roberts syndrome (RBS) are severe developmental maladies that arise from mutation of cohesin (including , CdLS) and (RBS). Though...
Cornelia de Lange syndrome (CdLS) and Roberts syndrome (RBS) are severe developmental maladies that arise from mutation of cohesin (including , CdLS) and (RBS). Though ESCO2 activates cohesin, CdLS and RBS etiologies are currently considered non-synonymous and for which pharmacological treatments are unavailable. Here, we identify a unifying mechanism that integrates these genetic maladies to pharmacologically-induced teratogenicity via thalidomide. Our results reveal that Esco2 and cohesin co-regulate the transcription of a component of CRL4 ubiquitin ligase through which thalidomide exerts teratogenic effects. These findings are the first to link RBS and CdLS to thalidomide teratogenicity and offer new insights into treatments.
Topics: Acetyltransferases; Cell Cycle Proteins; Chromosomal Proteins, Non-Histone; Craniofacial Abnormalities; DNA-Binding Proteins; De Lange Syndrome; Ectromelia; Humans; Hypertelorism; Ligases; Mutation; Receptors, Interleukin-17; Thalidomide; Ubiquitin; Ubiquitin-Protein Ligases; Cohesins
PubMed: 34989322
DOI: 10.1080/15384101.2021.2023304 -
Microorganisms Dec 2022Amidst the ongoing monkeypox outbreak, global awareness has been directed towards the prevention of viral transmission and case management, with the World Health... (Review)
Review
Amidst the ongoing monkeypox outbreak, global awareness has been directed towards the prevention of viral transmission and case management, with the World Health Organization declaring the outbreak a public health emergency of international concern. Monkeypox virus is one of several species in the Orthopoxvirus genus, with other species of the genus including the variola, cowpox, mousepox, camelpox, raccoonpox, skunkpox, and volepox viruses. Although the nomenclature of these species is based on the animal host from which they were originally isolated, transmission from animals to humans has been reported with several species. The progression of disease, following an incubation period, typically consists of a prodromal phase with systemic flu-like symptoms. Various organ systems may be affected in addition to the formation of pathognomonic skin lesions. As monkeypox poses a continued public health concern, the ophthalmic sequelae of monkeypox virus, especially those leading to vision loss, warrant consideration as well. This review provides a comprehensive summary of the ophthalmic implications of poxviruses in clinical and laboratory settings reported in the literature, as well as areas of unmet need and future research.
PubMed: 36557740
DOI: 10.3390/microorganisms10122487 -
Journal of Surgical Oncology Feb 2022Reconstruction following resection of sarcomas of the upper extremity with methods described in the prevalent literature may not be possible in few selected cases. We...
BACKGROUND
Reconstruction following resection of sarcomas of the upper extremity with methods described in the prevalent literature may not be possible in few selected cases. We describe surgical phocomelia or phoco-reduction as a method of limb salvage in such cases of extensive sarcomas of the upper limb with its functional and oncological outcomes.
METHODS
Evaluation of functional and oncological outcomes was performed for 11 patients who underwent surgical phocomelia or phoco-reduction for extensive sarcomas of the upper limb between 2010 and 2019.
RESULTS
The mean follow-up period in the study was 27.8 months. Five patients required a segmental resection including the entire humerus while six patients underwent segmental resection around the elbow with a mean resection length of 21.5 cm. Mean Musculoskeletal Tumor Society 93 score was 22 depicting a good functional outcome. Mean handgrip strength on the operated side was 62% of the contralateral side with preservation of useful hand function. Meantime to humeroulnar union was 6.7 months. Radial nerve palsy and implant failure occurred in one patient each. No patient developed local recurrence while three patients died of metastasis.
CONCLUSION
Surgical phocomelia is a prudent alternative to severely incapacitating amputations in situations where other reconstruction methods are not feasible.
Topics: Adolescent; Adult; Amputation, Surgical; Child; Female; Hand Strength; Humans; Limb Salvage; Male; Middle Aged; Retrospective Studies; Sarcoma; Upper Extremity; Young Adult
PubMed: 34599761
DOI: 10.1002/jso.26704 -
Simultaneous femoral and tibial lengthening for severe limb length discrepancy in fibular hemimelia.Journal of Orthopaedic Surgery and... Nov 2023Fibular Hemimelia (FH) is the most common longitudinal limb deficiency. Significant limb length discrepancy (LLD) will necessitate long treatment times and multiple... (Review)
Review
BACKGROUND
Fibular Hemimelia (FH) is the most common longitudinal limb deficiency. Significant limb length discrepancy (LLD) will necessitate long treatment times and multiple settings to compensate for LLD when associated with femoral shortening. This study evaluates the outcome of simultaneous femoral and tibial lengthening using the Ilizarov frame.
METHODS
This retrospective study included the cases of 12 children with severe limb length discrepancy caused by combined FH and ipsilateral femoral shortening from May 2015 to August 2022. The total LLD ranged from 7 to 14.5 cm. All patients underwent single-session femoral and tibial lengthening using the Ilizarov ring external fixator technique. Additional procedures were performed in the same setting, including Achilles tendon lengthening, fibular anlage excision, peroneal tendons lengthening, and iliotibial band release. Follow-up ranged from 2 to 4 years.
RESULTS
The planned limb lengthening was achieved in ten cases (83%). No cases of joint subluxation or dislocation were encountered. No neurovascular injury has occurred during the treatment course. In all cases, the bone healing index was better on the femoral side than on the tibia. Poor regeneration and deformity of the tibia occurred in two cases (16.6%).
CONCLUSION
Simultaneous femoral and tibial lengthening using the Ilizarov fixator is a relatively safe procedure with the result of correction of total LLD in one session in a shorter time and less morbidity.
Topics: Child; Humans; Tibia; Ectromelia; Retrospective Studies; Fibula; Bone Lengthening; Ilizarov Technique; Leg Length Inequality; Leg; Treatment Outcome
PubMed: 37936235
DOI: 10.1186/s13018-023-04229-y -
Disability and Rehabilitation Jun 2022Longitudinal fibular deficiency (LFD) is the most common congenital long bone deficiency. This study aimed to objectively assess the physical performance of children and...
PURPOSE
Longitudinal fibular deficiency (LFD) is the most common congenital long bone deficiency. This study aimed to objectively assess the physical performance of children and adolescents with LFD compared with unaffected peers, and to examine trends over age for subgroups of the LFD population.
METHODS
Differences between children with LFD and unaffected peers were examined with hand-held dynamometry for lower-limb muscle strength, Six-Minute Walk Test, Timed up and down stairs test, Star Excursion Balance Test, and Standing long jump.
RESULTS
Thirty-nine children with LFD and 284 unaffected peers participated. Children with LFD performed at a lower level than their unaffected peers, on all measures of physical performance (mean 2.1 -scores lower, all < 0.01), except in long jump ( = 0.27). When comparing the performance of children with LFD to their unaffected peers across four age groups, there was a significant between-groups difference on all strength measures, and on the Six-Minute Walk distance, between children with and without LFD. These differences were smallest in young children (3-6 years) and largest in the older children (15-18 years) (all < 0.01). Children with no lengthening surgery performed better on the Six-Minute Walk Test, covering a greater distance during the test, than those who had surgery (mean difference 83 metres, < 0.01). There were no significant differences between children who had or had not undergone an amputation.
CONCLUSIONS
Children with LFD performed at a significantly lower level than unaffected peers on all measures of physical performance other than jumping. The largest differences were in older children. This paper provides baseline functional data for future interventions in LFD.
LEVEL OF EVIDENCE
Cross-sectional study.Implications for RehabilitationThis paper provides the first baseline functional data using validated objective measures on a consecutive cohort of children and adolescents with longitudinal fibular deficiency.Children with LFD performed significantly worse than their unaffected peers on all measures of physical performance other than jumping, with children falling further behind their peers as they age.Children who undergo an amputation typically have the most severe anatomical presentation and yet perform at an equivalent functional level.This paper identifies multiple modifiable impairments that represent potential opportunities for rehabilitation professionals to target with conservative treatment options to improve functional performance.
Topics: Adolescent; Amputation, Surgical; Child; Child, Preschool; Cross-Sectional Studies; Ectromelia; Fibula; Humans; Physical Functional Performance
PubMed: 33331793
DOI: 10.1080/09638288.2020.1849420 -
Folia Medica Apr 2021Mermaid syndrome or sirenomelia is an extremely rare congenital malformation with an incidence between 1.5 and 4.2 per 1,000,000 pregnancies. Association of mermaid...
Mermaid syndrome or sirenomelia is an extremely rare congenital malformation with an incidence between 1.5 and 4.2 per 1,000,000 pregnancies. Association of mermaid syndrome with VACTERL-H syndrome is extremely rare, with only two cases reported so far in the literature. We present a new case of type I sirenomelia associated with VACTERL-H syndrome and review the relevant literature. A 15-year-old female patient was admitted to the Department of Pathological Pregnancy at St George University Hospital, Plovdiv with progredient abortion during her first pregnancy. She had low socioeconomic status, negative history of concomitant diseases and addictions. The patient avoided prophylactic intake of folic acid during her pregnancy. Prenatal ultrasound found a malformative fetus. Consequently, magnetic resonance imaging was performed which established the presence of hydrocephalus and defects in the lower part of the spine. These pathological findings indicated interruption of pregnancy at 20 weeks of gestation. The fetopathological examination found sirenomelia type I associated with myelomeningocele, hydrocephalus, anal imperforation, single umbilical artery, bilateral renal and ureteric agenesis, bladder agenesis, tracheo-esophageal fistula, agenesis of external genitals, monkey fold of the left palm of the hand, also known as VACTERL-H syndrome.Our case demonstrates that mermaid syndrome and VACTERL-H syndrome represent different manifestations of a single pathological process that results in disorders of the blastogenesis at different stages during embryonic development.
Topics: Adolescent; Anal Canal; Cardiovascular Abnormalities; Digestive System Abnormalities; Ectromelia; Esophagus; Female; Genetic Diseases, X-Linked; Heart Defects, Congenital; Humans; Hydrocephalus; Kidney; Limb Deformities, Congenital; Musculoskeletal Abnormalities; Pregnancy; Spine; Syndrome; Trachea
PubMed: 33932019
DOI: 10.3897/folmed.63.e52900 -
JNMA; Journal of the Nepal Medical... May 2022The complete absence of limbs is a rare occurrence. Though the causes are various, it is hard to elicit most of the time. They are usually diagnosed via anomaly scan but...
UNLABELLED
The complete absence of limbs is a rare occurrence. Though the causes are various, it is hard to elicit most of the time. They are usually diagnosed via anomaly scan but the lack of access to the same can often lead to a term presentation. It is still not uncommon to receive pregnant patients at term to the hospital or in labour as the first antenatal visit. Increasing the feasibility of the scan can help in the early diagnosis and management. Here, we report a rare combination of limb defects that we managed in a district-level hospital and highlight the difficulties in the management and referral of the patients while working in rural areas.
KEYWORDS
amelia; antenatal care; congenital limb deformities; fetal ultrasonography.
Topics: Abnormalities, Multiple; Ectromelia; Female; Humans; Limb Deformities, Congenital; Pregnancy; Prenatal Care; Ultrasonography, Prenatal
PubMed: 35633231
DOI: 10.31729/jnma.7486 -
Turk Patoloji Dergisi 2020Sirenomelia, which is also known as mermaid syndrome and characterized by the fusion of the lower extremities, is the most severe form of caudal regression syndrome and...
Sirenomelia, which is also known as mermaid syndrome and characterized by the fusion of the lower extremities, is the most severe form of caudal regression syndrome and one of the rare and lethal congenital malformations. The anomalies that might be seen in this syndrome include pelvic-sacral dysplasia, genital anomalies, bilateral pelvic renal fusion accompanied by renal dysplasia, colon atresia, unilateral umbilical artery, and imperforated anus. The incidence of sirenomelia is 0.8-1 cases in 60,000-100,000 deliveries and the male/female ratio is 2.7-3:1. The case reported in the present study was a 13-week-old male fetus 30 g in weight with a macerated appearance. The upper extremities had a relatively normal appearance but the lower extremities were conjoined and there was a single lower extremity consisting of conjoined feet and toes. In the face, the nasal bridge was sunken, the ears had a low position, and there were cleft palate and cleft lip. Examination of the external genital organs revealed that the penile part was in the anal region. There was no anus opening. The crown-rump length was 8.5cm, the heel-toe length was approx. 1cm, and the rump-heel length was approx. 3.7cm. There were none of the two kidneys, ureter, bladder, urethra, or rectum. In the umbilical cord, there were 2 venous structures, one of which was the artery. Perivillous congestion and hyperemia, perivillous calcification, deciduitis, and focal infarct regions were observed in placental tissues. This report aims to discuss this very rare case together with the literature.
Topics: Abnormalities, Multiple; Ectromelia; Female; Fetus; Humans; Male; Pregnancy
PubMed: 32525213
DOI: 10.5146/tjpath.2020.01491