-
Frontiers in Pediatrics 2023The clinical characteristics of Ulnar-mammary syndrome (UMS) caused by mutations in (T-Box transcription factor 3) were studied and the correlation between genotype and...
OBJECTIVE
The clinical characteristics of Ulnar-mammary syndrome (UMS) caused by mutations in (T-Box transcription factor 3) were studied and the correlation between genotype and clinical phenotype were analyzed to improve awareness and early diagnosis of the disease.
METHODS
The clinical data of a boy aged 13 years and 5 months with left forearm deformity and growth retardation as the main features were analyzed. Genomic exon detection was performed, and the results were verified by Sanger sequencing. Simultaneously, we performed literature review to analyze the correlation between clinical phenotypes and genotypes.
RESULTS
The clinical manifestations in the child were short stature, ulnar hypoplasia of the forearm, hypohidrosis, retracted nipple, micropenis, and cryptorchidism. Laboratory examination revealed hyperthyroidism, growth hormone deficiency, and hypogonadotropic hypogonadism. Imaging results displayed delayed bone age, small pituitary gland, and persistence of Rathke's cleft cyst. The results of the exome sequencing revealed the deletion of AGA at positions 1121-1,124 of , which resulted in a frameshift mutation (c.1121-1124del AGAG; pGlu374fs). According to the American College of Medical Genetics (ACMG) assessment, the mutation is a pathogenic variant. A definitive diagnosis of UMS was made on the basis of the clinical phenotype of the patient. The Chinese and English literature were reviewed to analyze the correlation between genotype and clinical phenotype.
CONCLUSION
UMS is a rare hereditary disease caused by mutations in . There is significant clinical heterogeneity associated with the variants of this gene. To our knowledge, this mutation site in has been reported for the first time, thereby expanding the mutation spectrum of this gene.
PubMed: 36937985
DOI: 10.3389/fped.2023.1052931 -
European Journal of Medical Genetics Feb 2012The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive multiple congenital malformation syndrome caused by dehydrocholesterol reductase deficiency. The...
The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive multiple congenital malformation syndrome caused by dehydrocholesterol reductase deficiency. The diagnosis is confirmed by high 7- and secondarily 8-dehydrocholesterol levels in plasma and tissues and/or by detection of biallelic mutations in the DHCR7 gene. The phenotypic spectrum of SLOS is broad, ranging from a mild phenotype combining subtle physical anomalies with behavioral and learning problems, to a perinatally lethal multiple malformations syndrome. The fetal phenotype of SLOS has been poorly described in the literature. We report a series of 10 fetuses with molecularly proven SLOS. Even in young fetuses, the facial dysmorphism appears characteristic. Genital abnormalities are rare in 46,XX subjects. Gonadal differentiation appears histologically normal and in agreement with the chromosomal sex, contrary to what has been previously stated. We observed some previously unreported anomalies: ulnar hypoplasia, vertebral segmentation anomalies, congenital pulmonary adenomatoid malformation, fused lungs, gastroschisis, holomyelia and hypothalamic hamartoma. This latter malformation proves that SLOS phenotypically overlaps with Pallister-Hall syndrome which remains clinically a major differential diagnosis of SLOS.
Topics: Diagnosis, Differential; Female; Fetus; Humans; Male; Observation; Phenotype; Smith-Lemli-Opitz Syndrome
PubMed: 22226660
DOI: 10.1016/j.ejmg.2011.12.002 -
Cureus Mar 2024This case study examines the rehabilitation process of a 24-year-old female patient with thalassemia major (TM), a hereditary hemoglobinopathy, who also suffered from...
This case study examines the rehabilitation process of a 24-year-old female patient with thalassemia major (TM), a hereditary hemoglobinopathy, who also suffered from distal ulnar hypoplasia, a congenital anomaly that causes pain and affects the wrist joint's strength and range of motion. The patient underwent a comprehensive physical rehabilitation program that aimed to address the challenges posed by ulnar hypoplasia. This program included a combination of customized exercises, splinting, and orthotic interventions to improve hand and wrist function. By adopting a multidisciplinary approach, the patient experienced significant improvements in mobility, strength, and overall quality of life. This case highlights the significance of personalized rehabilitation strategies in managing complex medical conditions, demonstrating the potential for positive outcomes even in patients with dual diagnoses of TM and ulnar hypoplasia.
PubMed: 38586800
DOI: 10.7759/cureus.55689 -
European Journal of Human Genetics :... Aug 2012Holt-Oram syndrome (HOS) is a rare autosomal dominant heart-hand syndrome due to mutations in the TBX5 transcription factor. Affected individuals can have structural...
Holt-Oram syndrome (HOS) is a rare autosomal dominant heart-hand syndrome due to mutations in the TBX5 transcription factor. Affected individuals can have structural cardiac defects and/or conduction abnormalities, and exclusively upper limb defects (typically bilateral, asymmetrical radial ray defects). TBX5 mutations reported include nonsense, missense, splicing mutations and exon deletions. Most result in a null allele and haploinsufficiency, but some impair nuclear localisation of TBX5 protein or disrupt its interaction with co-factors and downstream targets. We present a five generation family of nine affected individuals with an atypical HOS phenotype, consisting of ulnar ray defects (ulnar hypoplasia, short fifth fingers with clinodactyly) and very mild radial ray defects (short thumbs, bowing of the radius and dislocation of the radial head). The cardiac defects seen are those more rarely reported in HOS (atrioventricular septal defect, hypoplastic left heart syndrome, mitral valve disease and pulmonary stenosis). Conduction abnormalities include atrial fibrillation, atrial flutter and sick sinus syndrome. TBX5 mutation screening (exons 3-10) identified no mutations. Array comparative genomic hybridisation (CGH) revealed a 48 kb duplication at 12q24.21, encompassing exons 2-9 of the TBX5 gene, with breakpoints within introns 1-2 and 9-10. The duplication segregates with the phenotype in the family, and is likely to be pathogenic. This is the first known report of an intragenic duplication of TBX5 and its clinical effects; an atypical HOS phenotype. Further functional studies are needed to establish the effects of the duplication and pathogenic mechanism. All typical/atypical HOS cases should be screened for TBX5 exon duplications.
Topics: Abnormalities, Multiple; Adult; Chromosomes, Human, Pair 12; Comparative Genomic Hybridization; Computational Biology; DNA Copy Number Variations; Family; Female; Gene Duplication; Heart Defects, Congenital; Heart Septal Defects, Atrial; Humans; Lower Extremity Deformities, Congenital; Male; Phenotype; T-Box Domain Proteins; Upper Extremity Deformities, Congenital; Young Adult
PubMed: 22333898
DOI: 10.1038/ejhg.2012.16 -
Journal of Research in Medical Sciences... Sep 2013Ulnar hypoplasia is a rare longitudinal limb deficiency in which the ulna shows various degrees of deficiency. The condition is normally associated with radial defects,...
Ulnar hypoplasia is a rare longitudinal limb deficiency in which the ulna shows various degrees of deficiency. The condition is normally associated with radial defects, and in severe cases there is a reduction of postaxial/ulnar digits. Ulnar deficiency is an integral part of several syndromic malformations like Weyer's oligodactyly syndrome, limb/pelvis hypoplasia/aplasia syndrome, and ulnar-mammary syndrome. Here, we report an isolated unilateral ulnar deficiency in a boy who was a product of a consanguineous marriage. The subject demonstrated mesomelic shortening of the left arm with reduced zeugopod and autopod, and preaxial absence of two fingers. Additional findings in the affected limb were severe flexion contracture at the elbow joint, reduced and narrow palm, hypoplastic digits, and clinodactyly. Roentgenographic study revealed rudimentary ulna, dysplastic and posteriorly dislocated radius, crowding of carpals, and complete absence of digit rays of the thumb and index finger. Despite this anomaly, the subject could manage his daily life activities well. We present detailed clinical features and differential diagnosis of this rare limb malformation.
PubMed: 24381628
DOI: No ID Found -
European Journal of Human Genetics :... Mar 2020The HoxD cluster is critical for vertebrate limb development. Enhancers located in both the telomeric and centromeric gene deserts flanking the cluster regulate the...
The HoxD cluster is critical for vertebrate limb development. Enhancers located in both the telomeric and centromeric gene deserts flanking the cluster regulate the transcription of HoxD genes. In rare patients, duplications, balanced translocations or inversions misregulating HOXD genes are responsible for mesomelic dysplasia of the upper and lower limbs. By aCGH, whole-genome mate-pair sequencing, long-range PCR and fiber fluorescent in situ hybridization, we studied patients from two families displaying mesomelic dysplasia limited to the upper limbs. We identified microduplications including the HOXD cluster and showed that microduplications were in an inverted orientation and inserted between the HOXD cluster and the telomeric enhancers. Our results highlight the existence of an autosomal dominant condition consisting of isolated ulnar dysplasia caused by microduplications inserted between the HOXD cluster and the telomeric enhancers. The duplications likely disconnect the HOXD9 to HOXD11 genes from their regulatory sequences. This presumptive loss-of-function may have contributed to the phenotype. In both cases, however, these rearrangements brought HOXD13 closer to telomeric enhancers, suggesting that the alterations derive from the dominant-negative effect of this digit-specific protein when ectopically expressed during the early development of forearms, through the disruption of topologically associating domain structure at the HOXD locus.
Topics: Bone Diseases, Developmental; Cells, Cultured; Female; Gene Duplication; Homeodomain Proteins; Humans; Infant; Loss of Function Mutation; Male; Multigene Family; Phenotype; Upper Extremity Deformities, Congenital
PubMed: 31591517
DOI: 10.1038/s41431-019-0522-2 -
BMC Medical Genetics Jan 2013A partial duplication of the distal long arm of chromosome 5 (5q35-->qter) is known to be associated with a distinct phenotype referred to as Hunter-McAlpine syndrome....
BACKGROUND
A partial duplication of the distal long arm of chromosome 5 (5q35-->qter) is known to be associated with a distinct phenotype referred to as Hunter-McAlpine syndrome. Clinical spectrum of this disorder mainly consists of mental retardation, microcephaly, short stature, skeletal anomalies, and craniofacial dysmorphism featuring flat facies, micrognathia, large, low-set dysplastic ears, hypertelorism, almond-shaped, down-slanted palpebral fissures, epicanthal folds, small nose, long philtrum, small mouth, and thin upper lip. Less frequent remarkable findings include craniosynostosis, heart defect, hypoplastic phalanges, preaxial polydactyly, hypospadias, cryptorchidism, and inguinal hernia. In most patients with a partial duplication of 5q the aberration occurred due to an inherited unbalanced translocation, therefore the phenotype was not reflective of pure trisomy 5q.
CASE PRESENTATION
We report on a 9.5-year-old boy with some feature of Hunter-McAlpine syndrome including short stature, complex heart defect (dextrocardia, dextroversion, PFO), bilateral cryptorchidism, hypothyroidism, and craniofacial dysmorphism. Additionally, bilateral radial agenesis with complete absence of Ist digital rays, ulnar hypoplasia with bowing, choroidal and retinal coloboma, abnormal biliary vesicle were identified, which have never been noted in 5q trisomy patients. Karyotype analysis, sequencing and MLPA for TBX5 and SALL4 genes were unremarkable. Array comparative genomic hybridization detected a duplication on 5q35.2-5q35.3, resulting from a de novo chromosomal rearrangement. Our proband carried the smallest of all previously reported pure distal 5q trisomies encompassing terminal 5.4-5.6 Mb and presented with the most severe limb malformation attributed to the increased number of distal 5q copies.
CONCLUSIONS
We postulate that a terminal distal trisomy of 5q35.2-5q35.3, which maps 1.1 Mb telomeric to the MSX2 gene is causative for both radial agenesis and complex heart defect in our proband. A potential candidate gene causative for limb malformation in our proband could be FGFR4, which maps relatively in the closest position to the chromosomal breakage site (about 1.3 Mb) from all known 5q duplications. Since the limb malformation as well as the underlying genetic defect are distinct from other 5q trisomy patient we propose that a position effect resulting in altered long-range regulation of the FGFR4 (alternatively MSX2) may be responsible for the limb malformation in our proband.
Topics: Abnormalities, Multiple; Child; Chromosomes, Human, Pair 5; Cri-du-Chat Syndrome; Dwarfism; Face; Heart Defects, Congenital; Humans; Male; Radius; Thumb; Trisomy
PubMed: 23342975
DOI: 10.1186/1471-2350-14-13 -
The Journal of Veterinary Medical... Sep 2002Hemimelia is a congenital abnormality characterized by the absence of a portion of the normal structures in a limb. Hemimelia is classified as transversal and paraxial...
Hemimelia is a congenital abnormality characterized by the absence of a portion of the normal structures in a limb. Hemimelia is classified as transversal and paraxial and is related to genetical and environmental factors. This article shows the radiological findings observed in three different cases of paraxial hemimelia occurred in goats (radial agenesia, absence of the portion of the distal epiphysis of the radius and anomalous radius with ulnar hypoplasia). Possible causes related to these abnormalities are discussed.
Topics: Animals; Ectromelia; Female; Goats; Male; Radiography
PubMed: 12399612
DOI: 10.1292/jvms.64.843