scholarly journals Osteoglophonic Dysplasia: Phenotypic and Radiological Clues

2017 ◽  
Vol 06 (04) ◽  
pp. 247-251 ◽  
Author(s):  
Shwetha Kuthiroly ◽  
Dhanya Yesodharan ◽  
Aneesh Ghosh ◽  
Kenneth White ◽  
Sheela Nampoothiri
Keyword(s):  
Short Stature ◽  
Skeletal Dysplasia ◽  
Autosomal Dominant ◽  
Bone Age ◽  
Dominant Mode ◽  
Bone Lesions ◽  
Activating Mutations ◽  
Radiological Features ◽  
Proven Case ◽  
Mode Of Inheritance

AbstractOsteoglophonic dysplasia (OD) is an extremely rare, skeletal dysplasia with an autosomal dominant mode of inheritance. Rhizomelic dwarfism, craniosynostosis, impacted teeth, hypodontia or anodontia, and multiple nonossifying bone lesions are the salient features of this condition. We report a 14-year-old girl with clinical and radiological features consistent with OD. She presented with disproportionate short stature, craniosynostosis, a prominent supraorbital ridge, delayed teeth eruption, hypodontia, and multiple nonossifying bone lesions in the femur, tibia, and fibula. She had hypophosphatemia, which is a known association in this dysplasia. She also had advanced bone age, which is an unreported feature of this dysplasia. This condition is caused by activating mutations in FGFR1. A missense mutation was detected in the FGFR1, NM_001174067 (FGFR1_v001):c.1115G > A [p.(Cys372Tyr)] confirming the diagnosis; this is the first mutation-proven case to be reported from India.

scholarly journals Pseudoachondroplasia: Report on a South African family

2013 ◽  
Vol 17 (2) ◽  
pp. 65-67 ◽  
Author(s):  
Shahida Moosa ◽  
Gen Nishimura
Keyword(s):  
Short Stature ◽  
South African ◽  
Skeletal Dysplasia ◽  
Autosomal Dominant ◽  
Lower Limbs ◽  
Normal Length ◽  
Radiographic Features ◽  
Radiological Features

Pseudoachondroplasia is an autosomal dominant skeletal dysplasia that results in disproportionately short stature, severe brachydactyly with strikingly lax small joints, malalignments of the lower limbs, and characteristic radiological features. Although named ‘false achondroplasia’, the entity is a distinct condition, in which affected individuals are born with normal length and have a normal facies, but is often only recognised after the age of 2 years, when the disproportion and waddling gait become evident. We report on an affected South African father and daughter, and highlight their clinical and radiographic features.

scholarly journals The May-Hegglin Anomaly: Platelet Function, Ultrastructure and Chromosome Studies

Blood ◽  
1968 ◽  
Vol 32 (6) ◽  
pp. 950-961 ◽  
Author(s):  
JEANNE M. LUSHER ◽  
JOHN SCHNEIDER ◽  
I. MIZUKAMI ◽  
RUTH K. EVANS
Keyword(s):  
Platelet Function ◽  
Autosomal Dominant ◽  
Dominant Mode ◽  
Bleeding Tendency ◽  
Function Defect ◽  
Father And Son ◽  
Mode Of Inheritance

Abstract A father and son with the May-Hegglin anomaly were studied. Both were asymptomatic, although the father had a mild thrombocytopenia and a probable platelet thromboplastic function defect. Possible mechanisms for the bleeding tendency observed in approximately one-fourth of the persons with this anomaly are discussed. The autosomal dominant mode of inheritance is again demonstrated, and both father and son were found to have normal chromosomes.

scholarly journals The Hairy Family of Burma: A Four Generation Pedigree of Congenital Hypertrichosis Lanuginosa

1996 ◽  
Vol 89 (7) ◽  
pp. 403-408 ◽  
Author(s):  
J Bondeson ◽  
A E W Miles
Keyword(s):  
Nineteenth Century ◽  
Autosomal Dominant ◽  
Dominant Mode ◽  
Good Evidence ◽  
Show Business ◽  
Mode Of Inheritance

A Burmese family with congenital hypertrichosis lanuginosa had an eventful history in the nineteenth century. The earlier members of this family were employed at the court of Ava, but the later ones spent their lives in show business, being widely exhibited for money in the 1880s. Their extraordinary hairiness attracted much curiosity, and they were photographed several times. The hairy Burmese are the only example of a four-generation pedigree of congenital hypertrichosis lanuginosa, which is consistent with an autosomal dominant mode of inheritance. There is good evidence that, when the members of this family were hairy, their dentition was also deficient.

scholarly journals Bilateral coxa vara and tibia vara associated with severe short stature in a girl manifesting a constellation of bone lesions with exclusive involvement of the lower limbs

2018 ◽  
Vol 6 (3) ◽  
pp. 63-69
Author(s):  
Ali Al Kaissi ◽  
Franz Grill ◽  
Rudolf Ganger ◽  
Susanne Gerit Kircher
Keyword(s):  
Short Stature ◽  
Skeletal Dysplasia ◽  
Lower Limbs ◽  
Bone Lesions ◽  
Coxa Vara ◽  
Tibia Vara ◽  
Osteolytic Lesions ◽  
Fibrocartilaginous Dysplasia ◽  
Medial Cortex ◽  
Severe Short Stature

In most instances, a toddler is seen with unilateral varus of the tibia, usually the deformity appearing slightly more distal than the knee joint. Radiographs of the focal fibrocartilaginous dysplasia show a characteristic abrupt varus at the metaphyseal — diaphyseal junction of the tibia. Cortical sclerosis is in and around the area of the abrupt varus on the medial cortex. A radiolucency may appear just proximal to the area of cortical sclerosis. The aetiology of such defects and the pathogenesis of the deformity are mostly unknown. Many of the associated factors suggest that the condition at least partly results from a mechanical overload of the medioproximal tibial physis. The evaluation of a child with suspected pathologic tibia vara begins with a thorough history. A complete birth and developmental history should include the age at which the child begun walking. The medical history should identify any renal disease, endocrinopathies, or known skeletal dysplasia. The physical examination also should include the child’s overall lower extremity alignment and symmetry, hip and knee motion, ligamentous hyperlaxity, and tibial torsion. We describe on a 17 year-old-girl who manifests severe short stature associated with multiple orthopaedic abnormalities, namely, bilateral coxa vara and tibia vara. Radiographic documentation showed bilateral and symmetrical involvement of the lower limbs with the extensive form of fibrocartilaginous dysplasia, osteoporosis, and osteolytic lesions. The constellation of the malformation complex of osteolytic lesions, fibrocartilaginous changes and the polycystic like fibromas are not consistent to any previously published reports of fibrocartilaginous dysplasia. To the best of our knowledge, it seems that fibrocartilaginous changes are part of a novel type of skeletal dysplasia.

scholarly journals Clinical Characterization of Patients With Autosomal Dominant Short Stature due to Aggrecan Mutations

2016 ◽  
Vol 102 (2) ◽  
pp. 460-469 ◽  
Author(s):  
Alexandra Gkourogianni ◽  
Melissa Andrew ◽  
Leah Tyzinski ◽  
Melissa Crocker ◽  
Jessica Douglas ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Short Stature ◽  
Early Onset ◽  
Autosomal Dominant ◽  
Standard Deviation Score ◽  
Bone Age ◽  
Skeletal Maturation ◽  
Disc Disease ◽  
Phenotypic Spectrum ◽  
Median Height

Abstract Context: Heterozygous mutations in the aggrecan gene (ACAN) cause autosomal dominant short stature with accelerated skeletal maturation. Objective: We sought to characterize the phenotypic spectrum and response to growth-promoting therapies. Patients and Methods: One hundred three individuals (57 females, 46 males) from 20 families with autosomal dominant short stature and heterozygous ACAN mutations were identified and confirmed using whole-exome sequencing, targeted next-generation sequencing, and/or Sanger sequencing. Clinical information was collected from the medical records. Results: Identified ACAN variants showed perfect cosegregation with phenotype. Adult individuals had mildly disproportionate short stature [median height, −2.8 standard deviation score (SDS); range, −5.9 to −0.9] and a history of early growth cessation. The condition was frequently associated with early-onset osteoarthritis (12 families) and intervertebral disc disease (9 families). No apparent genotype–phenotype correlation was found between the type of ACAN mutation and the presence of joint complaints. Childhood height was less affected (median height, −2.0 SDS; range, −4.2 to −0.6). Most children with ACAN mutations had advanced bone age (bone age − chronologic age; median, +1.3 years; range, +0.0 to +3.7 years). Nineteen individuals had received growth hormone therapy with some evidence of increased growth velocity. Conclusions: Heterozygous ACAN mutations result in a phenotypic spectrum ranging from mild and proportionate short stature to a mild skeletal dysplasia with disproportionate short stature and brachydactyly. Many affected individuals developed early-onset osteoarthritis and degenerative disc disease, suggesting dysfunction of the articular cartilage and intervertebral disc cartilage. Additional studies are needed to determine the optimal treatment strategy for these patients.

scholarly journals Impaired growth and intracranial calcifications in autosomal dominant hypocalcemia caused by a GNA11 mutation

2016 ◽  
Vol 175 (3) ◽  
pp. 211-218 ◽  
Author(s):  
Sirpa Tenhola ◽  
Raimo Voutilainen ◽  
Monica Reyes ◽  
Sanna Toiviainen-Salo ◽  
Harald Jüppner ◽  
...  
Keyword(s):  
Short Stature ◽  
Autosomal Dominant ◽  
Clinical Symptoms ◽  
Urinary Calcium ◽  
Calcium Excretion ◽  
Clinical Genetic ◽  
Activating Mutations ◽  
Intracranial Calcifications ◽  
Healthy Family ◽  
Autosomal Dominant Hypocalcemia

Objective Autosomal dominant hypocalcemia (ADH) is characterized by hypocalcemia and inappropriately low PTH concentrations. ADH type 1 is caused by activating mutations in the calcium-sensing receptor (CASR), a G-protein-coupled receptor signaling through α11 (Gα11) and αq (Gαq) subunits. Heterozygous activating mutations in GNA11, the gene encoding Gα11, underlie ADH type 2. This study describes disease characteristics in a family with ADH caused by a gain-of-function mutation in GNA11. Design A three-generation family with seven members (3 adults, 4 children) presenting with ADH. Methods Biochemical parameters of calcium metabolism, clinical, genetic and brain imaging findings were analyzed. Results Sanger sequencing revealed a heterozygous GNA11 missense mutation (c.1018G>A, p.V340M) in all seven hypocalcemic subjects, but not in the healthy family members (n=4). The adult patients showed clinical symptoms of hypocalcemia, while the children were asymptomatic. Plasma ionized calcium ranged from 0.95 to 1.14mmol/L, yet plasma PTH was inappropriately low for the degree of hypocalcemia. Serum 25OHD was normal. Despite hypocalcemia 1,25(OH)2D and urinary calcium excretion were inappropriately in the reference range. None of the patients had nephrocalcinosis. Two adults and one child (of the two MRI scanned children) had distinct intracranial calcifications. All affected subjects had short stature (height s.d. scores ranging from −3.4 to −2.3 vs −0.5 in the unaffected children). Conclusions The identified GNA11 mutation results in biochemical abnormalities typical for ADH. Additional features, including short stature and early intracranial calcifications, cosegregated with the mutation. These findings may indicate a wider role for Gα11 signaling besides calcium regulation.

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