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European Journal of Medical Genetics Dec 2019Roberts/SC phocomelia syndrome (RBS/SC) is a rare autosomal recessive inherited condition characterized by prenatal-onset growth retardation, craniofacial anomalies, and...
Roberts/SC phocomelia syndrome (RBS/SC) is a rare autosomal recessive inherited condition characterized by prenatal-onset growth retardation, craniofacial anomalies, and symmetrical limb reduction defects. Here, we present two affected siblings with RBS/SC who have consanguineous parents. Both patients had intrauterine growth retardation; similar facial findings, including arched eyebrows, epicanthic folds, posteriorly angulated ears, and retrognathia; and hypopigmented patches on their skin. However, despite these common findings, the extremity involvement was different between the patients. The more severely affected boy had hypoplasia of the tibia and symmetrical agenesis of the radius, ulna, proximal carpal bones, and fibula. The slightly affected girl presented with mild symmetrical mesomelic shortening. The cytogenetic analysis showed aneuploidies at varying rates concerning different chromosomes in the analyses of different culture materials. As a remarkable finding in the cytogenetic studies, chromosome analysis of fibroblast cultures obtained from the hypopigmented skin region showed a much higher frequency of aneuploidy, especially trisomy 7, than normopigmented skin fibroblasts and lymphocyte cultures for both patients, which was also proven ex vivo by qPCR analyses from uncultured skin tissues. In the subsequent ESCO2 gene sequence analysis, both patients were found to be homozygous for the mutation c.1111dupA (p.Thr371Asnfs*32; NM_001017420.2), which is known to be pathogenic. In the literature search, only two RBS/SC patient reports with hypopigmented skin patches could be found. In addition, the presence of pigmentation defects in the embryo was reported in some different animal models for RBS/SC. When the literature review and study are evaluated together, hypopigmented patches can be considered as a rare finding for RBS/SC. It can be suggested that somatic aneuploidies seen in the natural course of the disease, especially aneuploidy of chromosome 7, which has many genes associated with pigmentation, may be responsible for the hypopigmentation patches.
Topics: Acetyltransferases; Adolescent; Aneuploidy; Child; Chromosomal Proteins, Non-Histone; Craniofacial Abnormalities; Ectromelia; Female; Humans; Hypertelorism; Male; Mutation; Skin; Skin Pigmentation
PubMed: 30590172
DOI: 10.1016/j.ejmg.2018.12.013 -
International Surgery Dec 1967
Topics: Adult; Ectromelia; Female; Humans; Pregnancy; Pregnancy Complications
PubMed: 6064726
DOI: No ID Found -
Journal of Hand Surgery (Edinburgh,... Jun 2003We studied 24 patients with 44 phocomelic upper limbs. Only 11 limbs could be grouped in the classification system of Frantz and O' Rahilly. The non-classifiable limbs...
We studied 24 patients with 44 phocomelic upper limbs. Only 11 limbs could be grouped in the classification system of Frantz and O' Rahilly. The non-classifiable limbs were further studied and their characteristics identified. It is confirmed that phocomelia is not an intercalary defect.
Topics: Abnormalities, Drug-Induced; Ectromelia; Humans; Radiography; Thalidomide
PubMed: 12809650
DOI: 10.1016/s0266-7681(02)00392-3 -
The Journal of Bone and Joint Surgery.... Dec 2005In contrast to longitudinal deficiencies, phocomelia is considered a transverse, intercalated segmental dysplasia. Most patients demonstrate severe, but not otherwise...
BACKGROUND
In contrast to longitudinal deficiencies, phocomelia is considered a transverse, intercalated segmental dysplasia. Most patients demonstrate severe, but not otherwise classifiable, upper-extremity deformities, which usually cannot be placed into one of three previously described phocomelia groups. Additionally, these phocomelic extremities do not demonstrate true segmental deficits; the limb is also abnormal proximal and distal to the segmental defect. The purpose of this investigation was to present evidence that upper-extremity abnormalities in patients previously diagnosed as having phocomelia in fact represent a proximal continuum of radial or ulnar longitudinal dysplasia.
METHODS
The charts and radiographs of forty-one patients (sixty extremities) diagnosed as having upper-extremity phocomelia were reviewed retrospectively. On the basis of the findings on the radiographs, the disorders were categorized into three groups: (1) proximal radial longitudinal dysplasia, which was characterized by an absent proximal part of the humerus, a nearly normal distal part of the humerus, a completely absent radius, and a radial-sided hand dysplasia; (2) proximal ulnar longitudinal dysplasia, characterized by a short one-bone upper extremity that bifurcated distally and by severe hand abnormalities compatible with ulnar dysplasia; and (3) severe combined dysplasia, with type A characterized by an absence of the forearm segment (i.e., the radius and ulna) and type B characterized by absence of the arm and forearm (i.e., the hand attached to the thorax).
RESULTS
Twenty-nine limbs in sixteen patients could be classified as having proximal radial longitudinal dysplasia. Systemic medical conditions such as thrombocytopenia-absent radius syndrome were common in those patients, but additional musculoskeletal conditions were rare. Twenty limbs in seventeen patients could be classified as having proximal ulnar longitudinal dysplasia. Associated musculoskeletal abnormalities, such as proximal femoral focal deficiency, were common in those patients. Eleven limbs in ten patients were identified as having severe combined dysplasia, which was type A in seven of them and type B in four. Four patients with severe combined dysplasia had congenital cardiac anomalies, and four had associated musculoskeletal abnormalities. Three of the four patients with the type-B disorder had a contralateral ulnar longitudinal dysplasia.
CONCLUSIONS
We propose that cases previously classified as upper-extremity phocomelia represent a spectrum of severe longitudinal dysplasia, as none of the sixty extremities that we studied demonstrated a true intercalary deficiency. These findings have both developmental and genetic implications.
Topics: Child; Child, Preschool; Ectromelia; Female; Humans; Infant; Male; Radiography; Retrospective Studies; Upper Extremity Deformities, Congenital
PubMed: 16322613
DOI: 10.2106/JBJS.D.02011 -
The Journal of Hand Surgery, European... Mar 2024We herein report on the application of a novel motorized prosthetic hand in a child with upper extremity phocomelia.
We herein report on the application of a novel motorized prosthetic hand in a child with upper extremity phocomelia.
Topics: Child; Humans; Ectromelia; Upper Extremity; Artificial Limbs; Upper Extremity Deformities, Congenital; Hand; Prosthesis Design
PubMed: 37882659
DOI: 10.1177/17531934231209645 -
Spine Deformity Jan 2023The purpose of this study is to present a case report of a patient with bilateral upper extremity phocomelia with progressive scoliosis, who underwent vertebral body...
PURPOSE
The purpose of this study is to present a case report of a patient with bilateral upper extremity phocomelia with progressive scoliosis, who underwent vertebral body tethering (VBT).
METHODS
This is a case report on the use of VBT in a patient with scoliosis and bilateral congenital phocomelia, with 5 year follow-up.
RESULTS
A male patient with bilateral phocomelia had early onset scoliosis that progressed to 45° at age 10. Surgical options were discussed, including traditional VBT, posterior spinal fusion, growing rods, magnetically controlled growing rods, and vertical expandible prosthetic titanium ribs. These options would limit the flexibility of the spine. Given these pitfalls, VBT was chosen, as it would address the scoliosis while maintaining trunk flexibility. Preoperatively, he had 45° right main thoracic curve, bending to 22°; he was Risser 0 with open triradiate cartilage. He underwent T6-T11 thoracoscopic VBT, with postoperative correction to 37°. Postoperatively, the patient was able to continue to use his lower extremities for writing, feeding, and personal grooming. He had no postoperative complications. At 3 years, his curve was 21°, and at 5 years was 19°.
CONCLUSION
This case describes a novel technique for treating scoliosis in patients with bilateral phocomelia. Other forms of scoliosis surgical treatment limit motion of the spine. Due to this, we present VBT as an option for this unique set of patients for correcting scoliosis, while also preserving trunk flexibility for its role in feeding and self-care.
Topics: Humans; Male; Child; Scoliosis; Thoracic Vertebrae; Vertebral Body; Ectromelia; Treatment Outcome
PubMed: 35918628
DOI: 10.1007/s43390-022-00562-0 -
Circulation Mar 1963
Topics: Drug Prescriptions; Ectromelia; Pharmacology; Thalidomide
PubMed: 13993506
DOI: 10.1161/01.cir.27.3.321 -
Indian Journal of Pathology &... 2009
Topics: Adult; Ectromelia; Female; Fetus; Humans; Pregnancy
PubMed: 19805983
DOI: 10.4103/0377-4929.56124 -
Anales Espanoles de Pediatria Sep 1988Three sibs with Roberts syndrome SC-phocomelia are presented. The first one, a nine years old girl, with a malformative syndrome consistent with SC-phocomelia:... (Review)
Review
Three sibs with Roberts syndrome SC-phocomelia are presented. The first one, a nine years old girl, with a malformative syndrome consistent with SC-phocomelia: symmetrical reductive malformations of the upper limbs; flexion contractures of both knee joints; multiple minor anomalies, including hemangioma of the face, hypoplastic nose, dysplastic ears and scanty, silvery blond hair; intrauterine and extrauterine growth retardation; psychomotor and mild mental retardation. Cytogenetic study reveals a centromeric abnormality consistent with an unusual sister chromatid disjunction in all metaphases, that can also be a useful tool in prenatal diagnosis. Next two sibs were males and offspring of a twin pregnancy and were found to have a malformative syndrome consistent with Roberts syndrome: low birth weight; dysplastic ears; hypertelorism, exophthalmos and cloudy corneas; bilateral cleft lip and cleft palate; severe reductive defects in both upper limbs and only syndactylia in the lower ones. Both sibs died soon after delivery. Autosomic recessive pattern of inheritance of this disorder, presentation in the same sibship of Roberts and SC-phocomelia syndromes, as different degrees of expression of the same disorder, and relationship of cytogenetic findings with cell division are discussed.
Topics: Child; Diseases in Twins; Ectromelia; Female; Humans; Infant, Newborn; Karyotyping; Male; Pedigree; Phenotype; Radiography; Syndrome
PubMed: 3057982
DOI: No ID Found -
Taiwanese Journal of Obstetrics &... Mar 2020To describe the ultrasonographic, pathologic and molecular findings in a fetus with TAR syndrome, and to illustrate the contribution of chromosomal microarray analysis...
OBJECTIVE
To describe the ultrasonographic, pathologic and molecular findings in a fetus with TAR syndrome, and to illustrate the contribution of chromosomal microarray analysis (CMA) to the etiological investigation of fetal upper limb reduction defects.
CASE REPORT
A 35-year-old woman was referred for Genetic Counseling after pregnancy termination for severe upper limb bilateral phocomelia detected in the second trimester. Fetal autopsy showed severe shortening of the arms and forearms. The fetal skeletal survey confirmed the absence of the radii, ulnae and humeri. CMA revealed an interstitial deletion in 1q21 including the RBM8A gene. Subsequent Sanger sequencing of this gene identified a hypomorphic mutant allele, c.-21G > A, confirming the diagnosis of TAR syndrome.
CONCLUSION
The differential diagnosis of upper limb defects is broad. Identification of their cause is essential for adequate genetic counseling including prognosis and recurrence risk estimation. CMA should be considered in fetuses with upper limb reduction defects, especially when the thumbs are present.
Topics: Aborted Fetus; Adult; Congenital Bone Marrow Failure Syndromes; Diagnosis, Differential; Ectromelia; Female; Genetic Counseling; Humans; Microarray Analysis; Pregnancy; Pregnancy Trimester, Second; Radius; Thrombocytopenia; Upper Extremity Deformities, Congenital
PubMed: 32127157
DOI: 10.1016/j.tjog.2020.01.024