Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 18 de 18
Filter
1.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(3): 257-259, 2019 Mar 10.
Article in Chinese | MEDLINE | ID: mdl-30835359

ABSTRACT

OBJECTIVE: To identify pathogenic mutation in a pedigree affected with brachydactyly and obesity. METHODS: Peripheral blood sample was collected for extraction of genomic DNA. Exons capture combined with next generation sequencing (NGS) was carried out to identify potential mutation. Sanger sequencing was used to verify the results. RESULTS: NGS has identified a novel heterozygous missense mutation (c.125A>C, p.Gln42Pro) in the exon 1 of PTHLH gene. The result was verified by Sanger sequencing. The mutations was derived from his mother. His uncle and sister have also carried the same heterozygous mutation. CONCLUSION: A novel mutation of the PTHLH gene has been identified in a pedigree affected with brachydactyly type E2 and obesity.


Subject(s)
Brachydactyly , Obesity/complications , Brachydactyly/complications , DNA Mutational Analysis , Humans , Mutation , Pedigree
2.
BMC Med Genet ; 19(1): 211, 2018 12 12.
Article in English | MEDLINE | ID: mdl-30541476

ABSTRACT

BACKGROUND: Tricho-rhino-phalangeal syndrome (TRPS) is a rare autosomal dominant genetic disorder characterized by distinctive craniofacial and skeletal abnormalities, while non-ossifying fibroma (NOF) is a common benign bone tumour in children and adolescents. To date, no case of TRPS coexisting with NOF has been reported. This report presents a 12-year-old girl who had the characteristic features of tricho-rhino-phalangeal syndrome and non-ossifying fibroma with a fibula fracture. CASE PRESENTATION: A 12-year-old girl was admitted to the Department of Endocrinology and Diabetes for evaluation of brachydactyly and a right fibula fracture. Clinical examination revealed sparse scalp hair, a characteristic bulbous pear-shaped nose, and brachydactyly with significant shortening of the fourth metatarsal. Neither intellectual disability nor multiple exostoses were observed. Radiography of both hands showed brachydactyly and cone-shaped epiphyses of the middle phalanges of the digits of both hands with deviation of the phalangeal axis. Genetic analysis of TRPS1 identified a heterozygous germline sequence variant (p.Ala932Thr) in exon 6 in the girl and her father. Approximately 1 month before being admitted to our department, the girl experienced a minor fall and suffered a fracture of the proximal fibula in the right lower limb. The pathological cytological diagnosis of the osteolytic lesion was NOF. Ten months following the surgery, the lesion on the proximal fibula of the girl disappeared. CONCLUSIONS: In conclusion, the present study is the first to report a rare case of NOF with a pathologic fracture in the fibula of a girl with TRPS. The identification of a missense mutation, (p.Ala932Thr), in exon 6 of TRPS1 in this kindred further suggested that the patient had type I TRPS and indicated that mutations in this exon may be correlated with more pronounced features of the syndrome. Radiological techniques and genetic analysis played key roles in the definitive diagnosis.


Subject(s)
Bone Neoplasms/genetics , Brachydactyly/genetics , DNA-Binding Proteins/genetics , Fibroma/genetics , Fingers/abnormalities , Fractures, Spontaneous/genetics , Hair Diseases/genetics , Langer-Giedion Syndrome/genetics , Neoplasms/genetics , Nose/abnormalities , Transcription Factors/genetics , Adult , Base Sequence , Bone Neoplasms/complications , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/pathology , Brachydactyly/complications , Brachydactyly/diagnostic imaging , Brachydactyly/pathology , Child , Exons , Female , Fibroma/complications , Fibroma/diagnostic imaging , Fibroma/pathology , Fibula/injuries , Fingers/diagnostic imaging , Fingers/pathology , Fractures, Spontaneous/complications , Fractures, Spontaneous/diagnostic imaging , Fractures, Spontaneous/pathology , Gene Expression , Hair Diseases/complications , Hair Diseases/diagnostic imaging , Hair Diseases/pathology , Humans , Langer-Giedion Syndrome/complications , Langer-Giedion Syndrome/diagnostic imaging , Langer-Giedion Syndrome/pathology , Male , Mutation , Neoplasms/complications , Neoplasms/diagnostic imaging , Neoplasms/pathology , Nose/diagnostic imaging , Nose/pathology , Paternal Inheritance , Radiography , Repressor Proteins
5.
Bone ; 85: 138-41, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26855372

ABSTRACT

BACKGROUND: Pseudohypoparathyroidism (PHP) is a genetic disorder characterized by resistance to the peripheral action of PTH due to maternally inherited heterozygous inactivating mutations in the coding sequence of Gsα or intronic regions of GNAS leading to aberrant splice variants (PHP1A), or methylation defects at GNAS (PHP1B). Brachydactyly is a clinical feature associated with both PHP1A and PHP1B, although it is more frequent in PHP1A patients. Loss-of-function mutations in PTHLH, the gene coding for parathyroid hormone related protein (PTHrP) were previously described in some patients with brachydactyly. Primary failure of tooth eruption (PFE) is related to some syndromes involving skeletal development, but it is also known as a nonsyndromic autosomal dominant condition. Previous studies showed that familial nonsyndromic PFE is caused by heterozygous mutations in the gene encoding the G protein-coupled receptor (PTH1R) for PTH and PTHrP. Thus, we hypothesized that PTHrP resistance could result in failure of tooth eruption (FTE) and/or brachydactyly in PHP. SUBJECTS AND METHODS: Nineteen patients with a molecular diagnosis of PHP underwent dental panoramic radiography (DPR), hand radiography and had their PTHrP levels measured. Patients with alterations at DPR were submitted to clinical dental evaluation. RESULTS: Nine patients had FTE and 7 patients had brachydactyly; 4 patients presented both features and none of them presented high PTHrP levels. Fourteen patients had PTHrP levels within the normal range and only one patient had slightly elevated PTHrP levels. Additionally, three novel GNAS mutations were described. CONCLUSION: We described the dental abnormalities in a large series of PHP patients that were followed in a single tertiary center. No relationship between plasma PTHrP levels and failure of tooth eruption, dental manifestations of PHP or brachydactyly was found. It is important that doctors pay attention to dental manifestations of the disease in order to refer patients to a proper care with dentists.


Subject(s)
Brachydactyly/blood , Brachydactyly/complications , Parathyroid Hormone-Related Protein/blood , Pseudohypoparathyroidism/blood , Pseudohypoparathyroidism/complications , Tooth Eruption , Adult , Child , Female , Humans , Male , Middle Aged , Young Adult
6.
Eur Rev Med Pharmacol Sci ; 19(23): 4549-52, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26698251

ABSTRACT

Here, we present of a 35-year old female diagnosed with an overlapping form of non-syndromic brachydactyly types D and E with phenotypic and radiological signs. There was observed to be shortening in the right hand metacarpal of 3rd and 4th fingers and left hand metacarpal of 4th finger and left foot metatarsal of 4th toe. There was also shortening of the distal phalanx of the thumbs and thoracic kyphosis. The syndromic form of brachydactyly type E is firmly associated with pseudo-hypopthyroidism as resistance to pthyroid hormone is the most prominent feature. As the patient had normal stature, normal laboratory parameters and no psychomotor developmental delay, the case was classified as isolated E type brachydactyly.


Subject(s)
Brachydactyly/complications , Foot Deformities, Congenital/complications , Hand Deformities, Congenital/complications , Adult , Brachydactyly/pathology , Female , Fingers/abnormalities , Foot Deformities, Congenital/pathology , Hand Deformities, Congenital/pathology , Humans
7.
Ophthalmology ; 122(8): 1555-62, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26077580

ABSTRACT

PURPOSE: To investigate the association of reticular pseudodrusen (RPD) with Sorsby fundus dystrophy (SFD). DESIGN: Prospective, monocenter, cross-sectional case series. SUBJECTS: Sixteen patients of 4 unrelated families with SFD caused by mutations in TIMP3. METHODS: All subjects underwent multimodal imaging including near-infrared (NIR) reflectance and fundus autofluorescence with a confocal scanning laser ophthalmoscope and spectral-domain optical coherence tomography (SD OCT). MAIN OUTCOME MEASURES: Prevalence, topographic distribution, and phenotype of RPD. RESULTS: Mean age of the investigated patients was 56.8 years (range, 23-78 years). Reticular pseudodrusen were identified frequently in SFD patients in the sixth decade of life (5 of 7 [71%]) and were absent in younger (n = 3) or older (n = 6) patients. They were most abundant in the superior quadrant and spared the foveal region. Reticular pseudodrusen appeared as yellowish round to oval (dot subtype; n = 5) or confluent, wriggled (ribbon subtype; n = 3) lesions, sometimes forming irregular networks. Reticular pseudodrusen were hyporeflective on NIR reflectance and hypofluorescent on fundus autofluorescence imaging. They appeared as subretinal deposits on SD OCT imaging. Other lesions, such as peripheral pseudodrusen and soft drusen, were present less frequently. CONCLUSIONS: Reticular pseudodrusen are a frequent finding in patients with SFD. Although SFD patients with RPD are younger, distribution and phenotype of RPD are similar to those observed in patients with age-related macular degeneration. The association of RPD with SFD implicates a role of Bruch's membrane, the Bruch's membrane-retinal pigment epithelium interface, or both in the pathogenesis of RPD.


Subject(s)
Brachydactyly/complications , Bruch Membrane/pathology , Coloboma/complications , Retinal Drusen/etiology , Retinal Pigment Epithelium/pathology , Adult , Aged , Brachydactyly/genetics , Coloboma/genetics , Cross-Sectional Studies , Female , Fluorescein Angiography , Humans , Male , Microscopy, Confocal , Middle Aged , Multimodal Imaging , Mutation , Ophthalmoscopy , Optical Imaging , Prevalence , Prospective Studies , Retinal Drusen/diagnosis , Tissue Inhibitor of Metalloproteinase-3/genetics , Tomography, Optical Coherence , Young Adult
10.
Rom J Morphol Embryol ; 55(2): 443-8, 2014.
Article in English | MEDLINE | ID: mdl-24969999

ABSTRACT

The hypodontia of a permanent tooth from a dental group represents a normal evolution in human dentition morphology. Nevertheless, the hypodontia of two teeth within a dental group is a rare developmental anomaly when not associated to a systemic syndrome. The aim of this study was to report two rare cases of four maxillary premolars hypodontia, not including the third molar, of two white women from the same family. There were presented clinical, radiological and genetic findings. These cases are of interest to practitioners for four aspects: the atypical phenotype of hypodontia, the complexity of craniofacial morphological changes, the autosomal dominant familial inheritance with variable expressivity and the difficult classification of diagnosis.


Subject(s)
Anodontia/complications , Bicuspid/abnormalities , Craniofacial Abnormalities/complications , Abnormalities, Multiple/diagnosis , Adult , Anodontia/diagnosis , Brachydactyly/complications , Brachydactyly/diagnosis , Craniofacial Abnormalities/diagnosis , Female , Humans , Pedigree , Siblings
11.
J Clin Sleep Med ; 10(3): 307-12, 2014 Mar 15.
Article in English | MEDLINE | ID: mdl-24634629

ABSTRACT

STUDY OBJECTIVE: The purpose of this study was to investigate the frequency of sleep disordered breathing (SDB) symptoms in a clinical sample of children with congenital craniofacial malformations (CFM) followed at a tertiary medical center and non-selected for sleep problems. METHODS: Cross-sectional study of 575 children aged 2-18 years followed at the Craniofacial Anomalies Program between March 2007 and May 2011. The Sleep-Related Breathing Disturbance scale of the Pediatric Sleep Questionnaire was used to screen for SDB, snoring, and sleepiness. A cutoff value ≥ 0.33 of the total answered questions identified children with positive screening for SDB symptoms. RESULTS: Overall, 25% of children screened positive for SDB, 28% for snoring, and 20% for sleepiness. In children with non-syndromic CFM, those with Robin sequence had the highest frequency of SDB, snoring, and sleepiness (43%, 44%, and 38%, respectively). In children with syndromic CFM, velocardiofacial/ DiGeorge syndrome had the highest frequency of SDB and sleepiness (48% and 43%, respectively). Children with Treacher Collins had the highest frequency of snoring (83%). The presence of cleft palate was not associated with an increased frequency of SDB symptoms. Nevertheless, children with syndromic CFM, compared to those with non-syndromic CFM, had a higher SDB score (0.27 ± 0.21 vs.0.21 ± 0.19, p = 0.003) and were more likely to have sleepiness (26% vs. 18%, p = 0.05). CONCLUSIONS: Congenital craniofacial malformations in children are associated with high risk for SDB symptoms. Our findings should encourage a high index of suspicion for SDB in children with CFM, with a low threshold for further testing and close follow-up. CITATION: Moraleda-Cibrián M; Edwards SP; Kasten SJ; Berger M; Buchman SR; O'Brien LM. Symptoms of sleep disordered breathing in children with craniofacial malformations.


Subject(s)
Craniofacial Abnormalities/complications , Sleep Apnea Syndromes/etiology , Adolescent , Brachydactyly/complications , Child , Child, Preschool , Cross-Sectional Studies , DiGeorge Syndrome/complications , Disorders of Excessive Somnolence/etiology , Facies , Female , Humans , Intellectual Disability/complications , Male , Mandibulofacial Dysostosis/complications , Pierre Robin Syndrome/complications , Snoring/etiology , Surveys and Questionnaires
12.
Eur J Hum Genet ; 21(6): 602-12, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23073310

ABSTRACT

The 2q37 locus is one of the most commonly deleted subtelomeric regions. Such a deletion has been identified in >100 patients by telomeric fluorescence in situ hybridization (FISH) analysis and, less frequently, by array-based comparative genomic hybridization (array-CGH). A recognizable '2q37-deletion syndrome' or Albright's hereditary osteodystrophy-like syndrome has been previously described. To better map the deletion and further refine this deletional syndrome, we formed a collaboration with the Association of French Language Cytogeneticists to collect 14 new intellectually deficient patients with a distal or interstitial 2q37 deletion characterized by FISH and array-CGH. Patients exhibited facial dysmorphism (13/14) and brachydactyly (10/14), associated with behavioural problems, autism or autism spectrum disorders of varying severity and overweight or obesity. The deletions in these 14 new patients measured from 2.6 to 8.8 Mb. Although the major role of HDAC4 has been demonstrated, the phenotypic involvement of several other genes in the deleted regions is unknown. We further refined the genotype-phenotype correlation for the 2q37 deletion. To do this, we examined the smallest overlapping deleted region for candidate genes for skeletal malformations (facial dysmorphism and brachydactyly), overweight, behavioural problems and seizures, using clinical data, a review of the literature, and the Manteia database. Among the candidate genes identified, we focus on the roles of PRLH, PER2, TWIST2, CAPN10, KIF1A, FARP2, D2HGDH and PDCD1.


Subject(s)
Behavior , Brachydactyly/complications , Brachydactyly/genetics , Chromosome Disorders/complications , Chromosome Disorders/genetics , Fibrous Dysplasia, Polyostotic/complications , Fibrous Dysplasia, Polyostotic/genetics , Intellectual Disability/complications , Intellectual Disability/genetics , Overweight/complications , Overweight/genetics , Adolescent , Adult , Child , Child, Preschool , Chromosome Deletion , Chromosome Mapping , Chromosomes, Human, Pair 2/genetics , Comparative Genomic Hybridization , DNA Copy Number Variations/genetics , Female , Genetic Association Studies , Humans , Male , Young Adult
13.
Am J Med Genet A ; 158A(11): 2894-8, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22987684

ABSTRACT

Grange syndrome is a disorder characterized by arterial occlusive disease, hypertension, congenital cardiac defects, bone fragility, brachysyndactyly, and learning disabilities. It was first described in four members of the same family and in two sporadic cases thereafter, suggesting the possibility of various patterns of inheritance. We report on the case of an 18-year-old female presenting with subarachnoid hemorrhage due to the rupture of a basilar artery aneurysm, and with distinctive systemic features including extensive vasculopathy, facial dysmorphisms and brachysyndactyly, consistent with the diagnosis of Grange syndrome. Although rare and not fully characterized, Grange syndrome should be included in the differential diagnosis of stroke at young age.


Subject(s)
Arterial Occlusive Diseases/complications , Brachydactyly/complications , Heart Defects, Congenital/complications , Hypertension/complications , Stroke/etiology , Syndactyly/complications , Adolescent , Bone and Bones/abnormalities , Cerebral Angiography , Facies , Female , Foot Deformities, Congenital , Hand Deformities, Congenital , Humans , Intracranial Aneurysm/diagnosis , Phenotype , Stroke/diagnosis , Subarachnoid Hemorrhage/diagnosis , Subarachnoid Hemorrhage/etiology
15.
Eur J Med Genet ; 55(4): 256-64, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22440536

ABSTRACT

Disproportionate short stature is a heterogeneous group of hereditary disorders, which are classified according to their mode of inheritance, their clinical skeletal and non-skeletal manifestations, and their radiological characteristics. Herein, we inform on eight individuals with severe disproportionate short stature from two unrelated consanguineous families of Arab-Muslim ancestry. The adult height of the affected individuals is between 112 cm and 127 cm, and is due to pre- and post-natal growth retardation, which probably manifests as early as the second trimester of pregnancy. At a young age, the phenotype is characterized by a short stature, a relatively large head, and a long triangular face, and this phenotype later evolves to one with in which the head is relatively small, the mandible is large and pointy. The affected individuals have normal cognitive abilities and lack any neurological deficits. Other typical features include a prominent nose, a voice with an unusual high-pitched sound, relatively small ears, clinodactyly, brachydactyly, small hands, hypoplastic fingernails, a waddling gait, and sparse hair post-pubertally. Typical skeletal changes include short long bones, especially the femurs and humeri, with mild metaphyseal changes and very short femoral necks. After due consideration of the other hereditary causes of disproportionate short stature and close examination of the pedigrees of the two families, we concluded that these eight individuals have the same hitherto unreported form of severe disproportionate short stature that is inherited in the autosomal recessive mode.


Subject(s)
Brachydactyly/genetics , Dwarfism/genetics , Hand Deformities, Congenital/genetics , Hypotrichosis/genetics , Adolescent , Adult , Arabs , Brachydactyly/complications , Child , Child, Preschool , Consanguinity , Dwarfism/complications , Female , Genes, Recessive , Hand Deformities, Congenital/complications , Humans , Hypotrichosis/complications , Infant , Male , Pedigree , Phenotype , Syndrome
16.
J Clin Res Pediatr Endocrinol ; 4(1): 42-4, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22394705

ABSTRACT

Pseudohypoparathyroidism (PHP) is a rare disorder characterized by varying degrees of unresponsiveness to parathyroid hormone. Patients usually present with hypocalcemia-induced seizures or tetany, whereas no case of hypocalcemia-induced cardiac arrhythmia in PHP has been described to date. In this paper, we report the case of a male adolescent with PHP type 1a who presented with hypocalcemia-induced ventricular extrasystoles (bigeminy, trigeminy) and mild corrected QT interval prolongation. The patient had brachydactyly and his second fingers and toes were longer than the others, a finding consistent with PHP. Laboratory tests detected hypomagnesemia, as well as elevated levels of creatine kinase and lactate dehydrogenase. Ventricular arrhythmia and abnormal laboratory tests improved with calcium supplementation and vitamin D treatment. The findings in this patient suggest that hypomagnesemia may make patients with PHP more susceptible to hypocalcemia and may thus prompt a state of hypocalcemia-induced arrhythmia or other cardiac complications.


Subject(s)
Pseudohypoparathyroidism/complications , Tachycardia, Ventricular/diagnosis , Adolescent , Brachydactyly/complications , Calcium/therapeutic use , Humans , Hypocalcemia/complications , Male , Tachycardia, Ventricular/drug therapy , Tachycardia, Ventricular/etiology , Treatment Outcome , Vitamin D/therapeutic use , Vitamins/therapeutic use
17.
J Autism Dev Disord ; 42(10): 2202-7, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22222775

ABSTRACT

Brachidactyly-Mental Retardation (BDMR) Syndrome (MIM 600430) is associated with terminal deletions at chromosome 2q37 and a limited number of studies also reported an association between 2q37 â†’ qter deletion and autism. Herein we describe two cases of autism in unrelated children with BDMR Syndrome, showing physical, cognitive, behavioral, and disease natural history homologies, with a very prominent social impairment in the first 4 years of life. At follow-up evaluations, spanning a 5-years period, both children experienced a progressive reduction of the autistic symptoms, besides retaining compromised cognitive ability. This report supports the hypothesis that genes in the 2q37 region may contribute to the etiology of autism, leading, however, to a peculiar evolution of the disease, with symptoms severity decreasing over time.


Subject(s)
Autistic Disorder/complications , Brachydactyly/complications , Chromosome Disorders/complications , Fibrous Dysplasia, Polyostotic/complications , Intellectual Disability/complications , Autistic Disorder/psychology , Brachydactyly/psychology , Child, Preschool , Chromosome Deletion , Chromosome Disorders/psychology , Chromosomes, Human, Pair 2 , Female , Fibrous Dysplasia, Polyostotic/psychology , Humans , Intellectual Disability/psychology , Male
18.
Kobe J Med Sci ; 56(6): E239-41, 2011 May 11.
Article in English | MEDLINE | ID: mdl-21937872

ABSTRACT

In a 80yo female with acute pancreatitis, myopathy, polyneuropathy, short stature, diabetes mellitus, hypothyroidism, hypoacusis, atrial fibrillation, hepatopathy, and renal cysts, mitochondrial disease was diagnosed. The family history for the disease was negative. Interestingly, the patient additionally presented with brachydactylia, which was also found in her son and father and has not been reported in association with mitochondrial disease before. Whether the relation between brachydactylia and mitochondrial disease was causal or coincidental remains speculative.


Subject(s)
Brachydactyly/complications , Mitochondrial Diseases/complications , Aged, 80 and over , Female , Humans
SELECTION OF CITATIONS
SEARCH DETAIL
...