Dominantly inherited mutations in COMP gene encoding cartilage oligomeric matrix protein may cause two dwarfing skeletal dysplasias, milder multiple epiphyseal dysplasia (MED) and more severe pseudoachondroplasia (PSACH). We studied the phenotype and X-rays of 11 patients from 5 unrelated families with different COMP mutations. Whole exome and/or Sangers sequencing were used for molecular analyses. Four to ten X-ray images of hands hips, knees or spine were available for each patient for retrospective analyses. Eight patients with MED have mutation c.1220G>A and 3 children with PSACH mutations c.1359C>A, c.1336G>A, or the novel mutation c.1126G>T in COMP. Progressive failure in growth developed in all patients from early childhood and resulted in short stature < 3rd percentile in 7 patients and very short stature < 1st percentile in four. Most patients had joint pain since childhood, severe stiffness in shoulders and elbows but increased mobility in wrists. Six children had bowlegs and two had knock knees. In all patients, X-rays of hands, hips and knees showed progressive, age-dependent skeletal involvement more pronounced in the epiphyses of long rather than short tubular bones. Anterior elongation and biconvex configuration of vertebral bodies were more conspicuous for kids. Six children had correction of knees and two adults had hip replacement. Skeletal and joint impairment in patients with MED and PSACH due to COMP mutation start in early childhood. Although the clinical severity is mutation and age dependent, many symptoms represent a continuous phenotypic spectrum between both diseases. Most patients may benefit from orthopaedic surgeries.
- MeSH
- achondroplazie MeSH
- chrupavkový oligomerní matrixový protein * genetika MeSH
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- matriliny genetika MeSH
- mutace * MeSH
- osteochondrodysplazie * diagnostické zobrazování genetika MeSH
- předškolní dítě MeSH
- retrospektivní studie MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
Asphyxiating thoracic dysplasia (ATD) represents a heterogeneous group of skeletal dysplasias with short ribs, narrow chest and reduced thoracic capacity. Mutations in several genes including IFT80, DYNC2H1, TTC21B and WDR19 have been found in patients with ATD. Both severe and milder course of the disease were described in correlation with secondary involvement of lung's function. Two children with attenuated form of ATD are described. Their anthropometric parameters for birth weight, length and head circumference were normal but narrow thorax was observed in both of them in early infancy with chest circumference < -3 SD (standard deviation) in comparison to age related controls. The postnatal adaptation and development of both children was uneventful except for mild tachypnoea in one of them which persisted till the age of 6 months. In both children, radiographs revealed narrow upper half of the chest with shorter ribs and atypical configuration of pelvis with horizontally running acetabula and coarse internal edges typical for ATD. Molecular analyses using whole exome sequencing in one family revealed that the patient is compound heterozygote in DYNC2H1 gene for a frame-shift mutation c.4458delT resulting in premature stop-codon p.Phe1486Leufs*11 and a missense mutation c.9044A>G (p.Asp3015Gly). The second family refused the DNA analysis. Regular monitoring of anthropometric parameters during childhood is of big importance both in health and disease. In addition, measurement of the chest circumference should be included, at least at birth and during infancy.
Hajdu-Cheney syndrome (HCS) is a rare multi-system disease with autosomal dominant inheritance and skeletal involvement, resulting mostly in craniofacial dysmorphy with mid-face hypoplasia, dental anomalies, short stature, scoliosis, shortening of the digits and nail beds, acro-osteolysis and osteoporosis. We report the progression of clinical and radiographic findings in five patients with Hajdu-Cheney syndrome from two families. A custom capture array designed to capture exons and adjacent intron sequences of 230 selected genes were used for molecular analyses, and the pathogenic variants identified were confirmed by PCR and Sanger sequencing. In both families we observed age-dependent changes in the disease, with a progression of pain in older patients, a shortening of digits and nail beds on both the hands and feet, kyphoscoliosis and the persistence of Wormian bones in lambdoid sutures. Molecular analyses performed in two patients revealed that they are heterozygotes for a c.6255T>A (p.Cys2085*) variant in the NOTCH2 gene, resulting in a premature stop-codon. Bone mineral density (Z-score < -2) did not improved in a girl treated with calcium and vitamin D supplementation during childhood and bisphosphonate during adolescence. Hajdu-Cheney syndrome is a slowly progressive disease with a frequently unfavourable prognosis in elderly patients, especially for the development of dental anomalies, osteoporosis and the progression of skeletal complications requiring orthopedic surgeries.
- MeSH
- dítě MeSH
- Hajdu-Cheney syndrom * komplikace patologie MeSH
- kostní denzita MeSH
- lidé MeSH
- mladiství MeSH
- osteoporóza * etiologie MeSH
- prognóza MeSH
- progrese nemoci MeSH
- senioři MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- buprenorfin škodlivé účinky MeSH
- diferenciální diagnóza MeSH
- injekce intravenózní * škodlivé účinky MeSH
- lidé MeSH
- mladiství MeSH
- pneumonie stafylokoková diagnóza etiologie terapie MeSH
- poruchy spojené s užíváním opiátů * diagnóza etiologie terapie MeSH
- poruchy spojené s užíváním psychoaktivních látek diagnóza epidemiologie MeSH
- sepse * diagnóza etiologie terapie MeSH
- stafylokokové infekce diagnóza etiologie terapie MeSH
- uživatelé drog MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
