scholarly journals SUN-LB19 Novel Homozygous Mutation in BMP1 Causing Osteogenesis Imperfecta

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Ishani Choksi ◽  
Thomas O Carpenter ◽  
Cemre Robinson
Keyword(s):  
Lumbar Spine ◽  
Osteogenesis Imperfecta ◽  
Laboratory Evaluation ◽  
Vertebral Compression Fractures ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Gene Products ◽  
Z Score ◽  
Rare Form ◽  
Minimal Trauma

Abstract Background: Osteogenesis imperfecta (OI) is characterized by bone fragility and increased fracture susceptibility. Most mutations occur in COL1A1 and COL1A2 genes. Rarely, mutations in BMP1 have been reported in association with OI type XIII. Disease severity is generally more severe when the mutation affects both gene products encoded by BMP1 that serve as procollagenases: bone morphogenic protein 1 and mammalian tolloid (mTLD) [1]. Clinical Case: A 7-year-old Hispanic boy, with speech and gross motor delays, sustained five bilateral tibial fractures with minimal trauma since age 2.5 years. At age 6 years, he developed severe back pain after a minor fall. Diffuse spinal osteopenia and multiple vertebral compression fractures (VCF) at T9, L1, L3 were identified radiographically, with progressive vertebral height loss in the ensuing 9 months. Fatigue was reported after walking >10 min, with difficulty running and climbing stairs. There was no family history of musculoskeletal disorders. Stature was consistently between 10-15th% for age. Subtle facial dysmorphism included micrognathia and small chin, with patchy blue-gray sclerae, and normal dentition. The lumbar spine was tender to percussion. Gait was slow and antalgic with external rotation of the right hip. Laboratory evaluation revealed normal serum calcium, iPTH, magnesium, phosphate, 25-hydroxyvitamin D and alkaline phosphatase for age. P1NP was slightly high (193 µg/L, 30-110 µg/L) and CTX was slightly low (554 pg/mL, n: 574-1849 pg/mL), the latter being atypical for OI. Total hip BMD (adjusted for height Z-score) was normal (Z-score = 1.76) and adjusted femoral neck BMD was high (Z-score = 2.67). VCFs precluded assessment of lumbar spine BMD. Genomic analysis revealed a homozygous missense mutation in exon 4 of BMP1 resulting in an amino acid substitution (c. C505T; p.Arg169Cys) in both the bone morphogenetic protein 1 and mTLD gene products of BMP1. The mutation is predicted to be damaging to both proteins, and associated with this rare form of OI. Conclusion: We report a novel homozygous mutation in BMP1 identified in a child with autosomal recessive OI. Unlike most forms of OI, patients with type XIII often have normal or increased BMD [1], making a correlation between BMD and fracture risk difficult. While bisphosphonates (BP) may help reduce recurrent fractures and provide symptomatic relief, the broad phenotypic spectrum and concern for further increasing BMD complicate management. A high resolution peripheral quantitative CT scan to assess bone microarchitecture and quality may aid in the decision of BP therapy. As evidence is limited on the effectiveness of BP in this rare form of OI, it is important to consider each case individually. 1. Sangsin, A., et al., Two novel compound heterozygous BMP1 mutations in a patient with osteogenesis imperfecta: a case report. BMC Med Genet, 2017. 18(1): p. 25.

Bone density and bone health alteration in boys with Duchenne Muscular Dystrophy: a prospective observational study

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Renu Suthar ◽  
B. V. Chaithanya Reddy ◽  
Manisha Malviya ◽  
Titiksha Sirari ◽  
Savita Verma Attri ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Bone Health ◽  
Prospective Observational Study ◽  
Bone Fractures ◽  
Long Bone ◽  
Vertebral Compression Fractures ◽  
Serum Osteocalcin ◽  
Z Score ◽  
X Ray ◽  
Compression Fractures

Abstract Objectives Boys with Duchenne Muscular Dystrophy (DMD) are at increased risk for compromised bone health, manifesting as low-impact trauma long bone fractures and vertebral compression fractures. Methods In a prospective observational study, we studied bone health parameters in North Indian boys with DMD. We consecutively enrolled ambulatory boys with DMD on glucocorticoid therapy. Bone health was evaluated with X-ray spine, Dual-energy X-ray absorptiometry (DXA), serum calcium, vitamin D3 (25[OH]D), 1,25-dihyroxyvitamin D3 (1,25[OH]2D3), serum osteocalcin, osteopontin, and N terminal telopeptide of type 1 collagen (Ntx) levels. Results A total of 76 boys with DMD were enrolled. The median age was 8.5 (interquartile range [IQR] 7.04–10.77) years. Among these, seven (9.2%) boys had long bone fractures, and four (5.3%) had vertebral compression fractures. Fifty-four (71%) boys underwent DXA scan, and among these 31 (57%) had low bone mineral density (BMD, ≤−2 z-score) at the lumbar spine. The mean BMD z-score at the lumbar spine was −2.3 (95% confidence interval [CI] = −1.8, −2.8), and at the femoral neck was −2.5 (95% CI = −2, −2.9). 25(OH)D levels were deficient in 68 (89.5%, n=76) boys, and 1,25(OH)2D3 levels were deficient in all. Mean serum osteocalcin levels were 0.68 ± 0.38 ng/mL (n=54), serum osteopontin levels were 8.6 ± 4.6 pg/mL (n=54) and serum Ntx levels were 891 ± 476 nmol/L (n=54). Boys with low BMD received glucocorticoids for longer duration, in comparison to those with normal BMD (median, IQR [16.9 (6–34) months vs. 7.8 (4.8–13.4) months]; p=0.04). Conclusions Bone health is compromised in North Indian boys with DMD. BMD at the lumbar spine is reduced in more than half of boys with DMD and nearly all had vitamin D deficiency on regular vitamin D supplements. Longer duration of glucocorticoid therapy is a risk factor for low BMD in our cohort.

scholarly journals AB0728 OSTEOGENESIS IMPERFECTA: ABOUT 12 CASES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1395.1-1395
Author(s):  
O. Jomaa ◽  
J. Mahbouba ◽  
S. Zrour ◽  
I. Bejia ◽  
M. Touzi ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Osteogenesis Imperfecta ◽  
Bone Densitometry ◽  
Calcium Supplementation ◽  
Hereditary Disease ◽  
Bone Fragility ◽  
Lower Limbs ◽  
Long Bone ◽  
Z Score ◽  
Average Serum

Background:Osteogenesis imperfecta (OI), is a rare hereditary disease characterized by bone fragility and low bone mass. The clinical presenatation is various with varying severity skeletal signs and inconstant extra-skeletal signs. Type 1 is the most common form (60% of cases).Objectives:Our objective is to describe the various clinical features observed over a period of 15 years.Methods:This is a retrospective descriptive study including 12 patients followed for OI, hospitalized in the Rheumatology Department at Fattouma Bourguiba Hospital Monastir TUNISIA between 2006 and 2019. Files were collected and analyzed.Results:They are 9 boys and 3 girls with an average age of 14.9 ± 8.6 years. Consanguinity was reported in 25% of cases. The reason leading to consultation was, recurrent fractures (75%), blue sclera (16.7), and bone deformity (8.3%). The number of previous fractures was on average of 5, all of which were caused by a low energy trauma. Similar family cases were noted in 41.6%. The mean age of the first fracture was 4.41 ± 3.2 years. The most frequent fracture sites were respectively: femur (7/12), leg (6/12), tibia (3/12), humerus (4/12), ankle (2/12), and forearm (2/12). A deformity was noted in 58.3% of the cases: lumbar kyphosis (2), exaggerated dorsal kyphosis (2), femurs in parenthesis (2), and an anarchic deformity of 2 lower limbs (1). Imperfect dentinogenesis was found in 8.3% of cases, while ENT examination revealed conductive and sensorineural hearing loss in 2 patients each. The main radiological abnormalities were diffuse bone demineralization (9 patients), cortical thinning (5 patients), vertebral compression (3 patients), and fracture (2 patients). The bone densitometry showed a mean Z score of 3.49±1.4 in the lumbar spine. The average serum calcium level was 2.38±1.15, alkaline phosphatases were elevated in all cases with an average of 756±624.9. The vitamin D level was deficient in all cases with an average of 22.75±5.3. All patients received in addition to the vitamin-calcium supplementation, pamidronate intravenously at a dose of 9mg/kg/year with a mean number of 6 cures. The main side effects observed during the infusion were abdominal pain, polyarthralgia and asthenia (1 patient), chest pain (1 patient) and fever and chills (1 patient). The control bone densitometry showed a mean Z score of 1.81±1.2 in the lumbar spine.Conclusion:Despite advances in the OI diagnosis and treatment, more research is needed. Bisphosphonate treatment decreases long-bone fracture rates, but such fractures are still frequent. New antiresorptive and anabolic agents are being investigated but efficacy and safety of these drugs, especially in children, need to be better established before they can be used in clinical practice.References:[1]https://doi.org/10.1097/med.0000000000000367Disclosure of Interests:None declared

P072 Lobstein's disease: about 12 observations

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_5) ◽  
Author(s):  
Olfa Jomaa ◽  
Jguirim Mahbouba ◽  
Zrour Saoussen ◽  
Bejia Ismail ◽  
Touzi Monji ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Osteogenesis Imperfecta ◽  
Bone Densitometry ◽  
Calcium Supplementation ◽  
Lower Limbs ◽  
University Hospital ◽  
Z Score ◽  
Blood Calcium ◽  
Vitamin D Levels ◽  
The Mean

Abstract Background Osteogenesis imperfecta (OI), or Lobstein's disease, is a rare inherited disorder characterized by bone fragility and low bone mass. The symptoms are diverse, with varying severity of skeletal signs and inconstant extra-skeletal signs. Type 1 is the most frequent form (about 60% of cases). Our objective is to describe the different clinical pictures hospitalized in our department during the last 15 years. Patients and methods This is a retrospective descriptive study including 12 patients followed for OI, hospitalized in the rheumatology department of Fattouma Bourguiba University Hospital Monastir TUNISIA between 2006 and 2019. The records were collected and analyzed. Results There were 9 boys and 3 girls with a mean age of 14.9 ± 8.6 years. Consanguinity was reported in 25% of cases. The chief reason for consultation was recurrent fractures (75%), blue sclera (16.7), and bone deformation (8.3%). The average number of anterior fractures was 5, with low-energy trauma as the mechanism in all cases. Similar cases in the family were noted in 41.6% of cases, in siblings in 25% of cases. The mean age of the first fracture was 4.41 ± 3.2 years. The most frequent fracture sites were respectively: femur (7/12), leg (6/12), tibia (3/12), humerus (4/12), ankle (2/12), and forearm (2/12). The deformity was noted in 58.3% of cases: lumbar kyphosis (2), exaggerated dorsal kyphosis (2), bracketed femurs (2), and anarchic deformity of 2 lower limbs (1). Dentinogenesis imperfecta was found in 8.3% of cases, while ENT examination revealed a conductive and sensorineural hearing loss in 2 patients each. The main radiological abnormalities were diffuse bone demineralization in 9 patients, thinning of the cortical bone in 5 patients, vertebral fractures in 3 patients, and fracture in 2 patients. Bone densitometry showed a mean Z-score of 3.49 ± 1.4 in the lumbar spine. The mean blood calcium level was 2.38 ± 1.15, alkaline phosphatase was elevated in all cases with a mean of 756 ± 624.9, and vitamin D levels were deficient in all cases with a mean of 22.75 ± 5.3. In addition to vitamin-calcium supplementation, all patients received intravenous pamidronate at a dose of 9 mg/kg/year with an average of 6 courses. The main side effects noted at the time of infusion were abdominal pain, polyarthralgia and asthenia (1 patient), chest pain (1 patient), and fever and chills (1 patient). Control bone densitometry showed a mean Z score of 1.81 ± 1.2 in the lumbar spine. Conclusions Osteogenesis imperfecta is a severe disease with a risk of serious complications t. In the absence of etiological treatment, symptomatic management must be both early and multidisciplinary.

Type 3 Von Willebrand Disease: Plasma Versus Platelets.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3059-3059 ◽  
Author(s):  
Walter H.A. Kahr ◽  
Fred G Pluthero ◽  
Victor S Blanchette ◽  
Katherine Sue Robinson ◽  
David Lillicrap ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Frameshift Mutation ◽  
Conflicts Of Interest ◽  
Von Willebrand Disease ◽  
Laboratory Evaluation ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Type 3 ◽  
Von Willebrand ◽  
Index Cases

Abstract Abstract 3059 Poster Board II-1035 Type 3 von Willebrand disease (VWD) is characterized by the virtual absence of von Willebrand factor (VWF) in plasma. Affected individuals are usually either homozygous or compound heterozygous for mutations that have been identified throughout the 52 exon VWF gene (listed in the ISTH SSC VWF database, http://www.sheffield.ac.uk/vwf/index.html). Most are null mutations associated with deletions, insertions, frameshifts, splicing defects and premature stop codons, however, a number of missense mutations have also been identified. VWF is normally stored in the Weibel-Palade bodies of vascular endothelial cells and within platelet alpha granules. Thus, the absence of plasma VWF in type 3 VWD patients carrying non-null mutations could be explained by one or more of: 1) premature mRNA degradation; 2) improper folding or assembly of VWF within cells resulting in proteolytic degradation; 3) rapid clearance of defective VWF molecules from plasma; 4) inability of synthesized VWF to be properly stored and/or released. We set out to detect type 3 VWD patients with possible VWF plasma clearance, storage or release defects by measuring the relative amounts of VWF in platelets and plasma, reasoning that such defects may be associated with the accumulation of VWF in platelets. Blood was prospectively collected from 21 previously diagnosed cases. Laboratory evaluation confirmed type 3 VWD, if the VWF:Ag and VWF:RCo levels were '5 IU per dL or if the VWF:Ag or VWF:RCo levels were 6-10 IU per dL accompanied by FVIII levels of '10 IU per dL. From this cohort, 16 unrelated type 3 VWD index cases were identified. Equivalent amounts of plasma and platelet lysates were analyzed for VWF by immunoblotting. As expected, platelet and plasma VWF were observed to be very low or absent in most cases. Interestingly, 5 patients were found to have relatively more (∼10 fold) platelet than plasma VWF using semiquantitative immunoblotting and equivalent sample loading. Type 3 VWD index cases together with available type 1 VWD siblings were subjected to VWF gene sequencing analyses. VWF exons 1-52 as well as ∼1500 bp of the promoter and intron/exon boundaries were sequenced. Strategies to identify partial gene deletions are ongoing. VWF gene mutations were identified in 12/16 patients. Surprisingly, in 4 out of the 5 patients with discrepant VWF content in plasma and platelets, no mutation in the VWF gene was identified by sequencing, suggesting either that an in-frame partial deletion or intronic VWF mutation may be present or that other genes such as those regulating the assembly, storage or release of VWF could be affected. A novel homozygous frameshift mutation at position c.8418_8419 resulting from a TCCC insertion was identified in one case. The presence of platelet VWF in this patient suggests that despite this frameshift mutation, VWF is expressed and packaged into platelets. Two siblings with the same homozygous mutation had an identical pattern (no plasma VWF but platelet VWF present) whereas two heterozygous siblings had 10-30% plasma VWF:Ag with normal amounts of platelet VWF. Studies are underway to determine whether increased clearance or defects in storage and/or release from endothelial cells or platelets are the cause of absent plasma VWF. Our studies also suggest that type 3 VWD can be subcategorized into subtype 0 (no plasma no platelet VWF) versus subtype P (no plasma but platelet VWF present) by measuring plasma and platelet VWF. We hypothesize that patients with type 3 VWD with platelet-harbouring VWF may have milder clinical manifestations compared to the subtype 0, however further studies are needed to test this proposal. Disclosures No relevant conflicts of interest to declare.

P013 Serum osteoprotegerin and RANKL in patients with Juvenile Idiopathic Arthritis and their correlation with bone mineral density

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_5) ◽  
Author(s):  
Radwa Helmy Shalaby ◽  
Elham Mohamed Kassem ◽  
Nagat Mohamed El-Gazzar ◽  
Sahar Ahmed Fathy Hammoudah ◽  
Amal Mohamed El-Barbary
Keyword(s):  
Bone Mineral Density ◽  
Juvenile Idiopathic Arthritis ◽  
Lumbar Spine ◽  
Bone Mineral ◽  
Disease Duration ◽  
Serum Levels ◽  
Z Score ◽  
Low Bone Mass ◽  
Mineral Density ◽  
Serum Rankl

Abstract Background Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic arthropathy of childhood and is associated with low bone mass, and may hasten the onset of osteoporosis later in life1. Bone loss occurs because of an imbalance between osteoclasts-activating factors like receptor activator of nuclear factor-κB ligand (RANKL) and its inhibitor osteoprotegerin (OPG) 2. Dual energy X-ray absorptiometry (DXA) is the preferred method for measuring bone mineral density (BMD) in children and to identify and follow individuals at risk for fracture 3. The objective is the Evaluation of serum levels of osteoprotegerin and RANKL and their correlation with BMD in JIA patients. Methods Forty JIA patients (according to the revised classification criteria of ILAR) and 40 healthy children individually matched for age, sex and race were included in this study. Children excluded from the study were those with primary and secondary causes of osteoporosis (such as chronic illness). All patients were assessed clinically by: age, sex, body mass index, type of JIA, disease duration and disease activity (by Juvenile Arthritis Disease Activity Score; JADAS 10). The functional disability was assessed by the Childhood Health Assessment Questionnaire (CHAQ). Blood samples were collected from JIA patients and healthy controls to determine serum levels of OPG and RANKL by ELISA. DXA scans were done using GE Healthcare Lunar DPX, Madison, Wisconsin. Bone mineral density of the L1-L4 lumbar spine and total body less head (TBLH) was evaluated in g/cm2 and expressed as Z score for age, sex according to the reference data given for this equipment. Results The study included 40 patients (25 females) with a mean age of 11.14 years and median disease duration of 2.5 years. As regard JIA type, 45% of patients were oligoarticular, 32.5% were polyarticular, and 22.5% were systemic JIA. Median JADAS 10 was 13.95. Patients (especially polyarticular JIA) had significantly higher serum RANKL levels and lower serum OPG and OPG/RANKL ratio when compared with controls (with p-value <0.001, 0.032 and <0.001 respectively). A diagnosis of low BMD (BMD Z-score ≤ -2) was given in 25% of patients (15% polyarticular and 10% systemic) by DXA of lumbar spine, and 20% (10% polyarticular and 10% systemic) by DXA of TBLH. On the other hand, no patient was given a diagnosis of osteoporosis (BMD Z-score ≤ -2 and a significant fracture history). Low BMD at lumbar spine and TBLH was negatively correlated with serum RANKL while positively correlated with OPG/RANKL ratio. Moreover, low BMD at lumbar spine was positively correlated with serum OPG level Conclusion High RANKL and low OPG levels appear to be associated with low bone mass in JIA patients. Patients with JIA (especially polyarticular and systemic subtype) are at increased risk of low bone mineral mass. Disclosure of Interests None declared

scholarly journals BMD status of Postmenopausal Women in relation with BMI: A study with 93 cases

2016 ◽  
Vol 17 (2) ◽  
pp. 138-141
Author(s):  
Samira Sharmin ◽  
Mabubul Haque ◽  
Syedur Rahman Miah ◽  
Md Mahbub Ur Rahman ◽  
Jasmine Ara Haque ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Femoral Neck ◽  
Postmenopausal Women ◽  
Lumbar Vertebrae ◽  
The Body ◽  
Mineral Density ◽  
Cross Sectional ◽  
T Score ◽  
Minimal Trauma ◽  
The Mean

Objectives: Low bone mass is a common disorder in elderly population which predisposes to fracture with minimal trauma. This study was performed to find out the association between the Body Mass Index (BMI) and Bone Mineral Density (BMD) in postmenopausal women.Materials and Methods: This cross sectional study was carried out at Institute of Nuclear Medicine and Allied Sciences Comilla and Mitford, Dhaka over a period of 12 months from January 2013 to December 2013. A total 93 postmenopausal women were enrolled for this study. All postmenopausal women underwent a BMD scan of femoral neck and lumbar vertebrae using a Dual Energy X-ray Absorptiometry (DEXA). Participants were categorized into three groups according to their age and BMI. BMD were expressed base on T-score according to WHO criteria. The relation among BMI, age and BMD were assessed.Results: The results of this study showed that the mean age of the study group was 57.13±7.49 years with range of 46 to 75 years. The most postmenopausal women were in age group 55-65years. The mean BMI of the study subjects were 24.18±5.08 kg/m2 with a range of 15.62 to 36.20 kg/m2. Among 93 subjects osteopenia was greater at lumbar spine (45.2%) with T-score mean±SD-1.83±0.33 and osteoporosis at femoral neck (51.6%) with T-score mean ±SD-3.36±-0.67. Pearson’s correlation coefficient test showed inverse relationship between age and BMD both lumbar spine (r = -0.301, p = 0.003) and femoral neck (r = -0.303, p=0.003) whereas the positive relation between BMI and BMD both at lumbar spine (r=0.338, p=0.001) and femoral neck (r =0.343, p=0.001). These showed that with advancing age, BMD decreases and the risk of osteoporosis increases and with increasing BMI, BMD increases and risk of osteoporosis decreases.Conclusion: The findings of this study portrait that aging and low BMI are risk factors associated with bone loss. So preventive measure should be taken for high risk post menopausal women.Bangladesh J. Nuclear Med. 17(2): 138-141, July 2014

Success ful Kyphoplasty in the Presence of Severe Retropulsion of Lumbar Spine without Neurological Deficits

2020 ◽  
pp. 127-130
Author(s):  
Ruben H. Schwartz
Keyword(s):  
Lumbar Spine ◽  
Compression Fracture ◽  
Disease Process ◽  
The Elderly ◽  
Fracture Pattern ◽  
Neurological Deficits ◽  
Vertebral Compression Fractures ◽  
Common Disease ◽  
Fracture Formation ◽  
Increased Risk

Background: Vertebral compression fractures are common causes of back pain in the aging patient population. Osteoporosis is an extremely common disease process within the elderly population, especially females, placing these patients at an increased risk of compression fracture formation. Besides pain, the fracture pattern can increase the risk of neurological compromise as well. Retropulsed fragments of the vertebral body cause impingement on the spinal canal and can be catastrophic. Case Report: We present the case of a 72-year-old man with 5 mm retropulsion of the lumbar spine at the L1 level without signs of neurological compromise. This extensive amount of retropulsion causing no signs of weakness is rare. He was subsequently successfully treated with kyphoplasty after failed conservative therapies. Conclusions: A case by case basis must be utilized when considering kyphoplasty for patients with retropulsion of the spine. If a patient’s pain persists after conservative therapy, then kyphoplasty can be utilized with full knowledge of the risks involved. Key words: Retropulsion, kyphoplasty, lumbago, spinal stenosis

scholarly journals NOVEL XRCC4 MUTATIONS IN AN INFANT WITH MICROCEPHALIC PRIMORDIAL DWARFISM, DILATED CARDIOMYOPATHY, SUBCLINICAL HYPOTHYROIDISM, AND EARLY DEATH: EXPANDING THE PHENOTYPE OF XRCC4 MUTATIONS

2020 ◽  
Vol 6 (1) ◽  
pp. e1-e4
Author(s):  
Meghan E. Fredette ◽  
Kristin C. Lombardi ◽  
Angela L. Duker ◽  
Catherine O. Buck ◽  
Chanika Phornphutkul ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Dilated Cardiomyopathy ◽  
Subclinical Hypothyroidism ◽  
Reference Range ◽  
Postnatal Growth ◽  
Left Ventricular ◽  
Female Infant ◽  
Compound Heterozygous ◽  
Z Score ◽  
Primordial Dwarfism

Objective: Microcephalic primordial dwarfism (MPD) is a group of clinically and genetically heterogeneous disorders which result in severe prenatal and postnatal growth failure. X-ray repair cross-complementing protein 4 ( XRCC4) is a causative gene for an autosomal recessive form of MPD. The objective of this report is to describe novel XRCC4 mutations in a female infant with MPD, dilated cardiomyopathy, and subclinical hypothyroidism. Methods: Genetic testing was performed using a comprehensive next generation sequencing panel for MPD, followed by targeted XRCC4 gene sequencing. Results: We report the case of a 970-gram, 35-cm, female infant (weight z score −5.05, length z score −4.71) born at 36 weeks and 3 days gestation. Physical examination revealed triangular facies, micrognathism, clinodactyly, and second and third toe syndactyly. Initial echocardiogram at birth was normal. Follow-up echocardiogram at 60 days of life revealed dilated cardiomyopathy with moderate left ventricular systolic dysfunction (ejection fraction was 40 to 45%), and anticongestive therapy was initiated. Thyroid testing revealed subclinical hypothyroidism with elevated thyroid-stimulating hormone of 13.0 μIU/mL (reference range is 0.3 to 5.0 μIU/mL) and normal free thyroxine by dialysis of 1.6 ng/dL (reference range is 0.8 to 2.0 ng/dL). Levothyroxine was initiated. Postnatal growth remained poor (weight z score at 3 months −4.93, length z score at 3 months −6.48), including progressive microcephaly (head circumference z score at 3 months −10.94). Genetic testing revealed novel compound heterozygous XRCC4 variants in trans: c.628A>T and c.638+3A>G. The child ultimately had cardiopulmonary arrest and died at 6 months of life. Conclusion: Molecular diagnosis in MPD is key to defining the natural history, management, and prognosis for patients with these rare disorders.

scholarly journals Osteogenesis imperfecta: a case report

2014 ◽  
Vol 43 (1) ◽  
pp. 30-32
Author(s):  
Ratu Rumana Binte Rahman ◽  
Shamasunnahar Begum
Keyword(s):  
Osteogenesis Imperfecta ◽  
Pulmonary Hypoplasia ◽  
Bone Fragility ◽  
Lower Limbs ◽  
Inherited Disease ◽  
Multiple Fractures ◽  
X Ray ◽  
Medical College ◽  
Minimal Trauma ◽  
Hallmark Feature

Osteogenesis Imperfecta is a inherited disease of connective tissue. Its hallmark feature is bone fragility with a tendency to fracture from minimal trauma or from the work of bearing weight against gravity. The disorder may occur in one out of 20,000 to one out of 60,000 live births, affecting both male and female of all races. We present a 38 year lady who gave birth to baby with osteogenesis imperfecta in Sir Salimullah Medical College & Mitford Hospital, Dhaka. Both lower limbs appeared shortened with thick musculo-cutaneous folds. Both the femoral shafts were shortened, deformed and fragmented. Both the humeral and fibular shafts were deformed and the presentation was breech. Her sclerae was blue. X-ray showed multiple fractures in humerus, femur and ribs and also right sided pulmonary hypoplasia. DOI: http://dx.doi.org/10.3329/bmj.v43i1.21376 Bangladesh Med J. 2014 January; 43 (1): 30-32

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