1/40. Recessively inherited multiple epiphyseal dysplasia with normal stature, club foot, and double layered patella caused by a DTDST mutation.We have observed over 25 different mutations in the diastrophic dysplasia sulphate transporter gene (DTDST) in association with the recessive disorders achondrogenesis 1B, atelosteogenesis 2, and diastrophic dysplasia. The c862t (R279W) transition is the most common mutation in non-Finnish patients, but in these disorders it is usually combined with other DTDST mutations. We had not seen a case of homozygosity for c862t (R279W) until we analysed dna from a 36 year old male with tall-normal stature (180 cm) who asked for genetic counselling for suspected multiple epiphyseal dysplasia. He was treated for club foot and hip dysplasia at birth. Skeletal changes consistent with multiple epiphyseal dysplasia, with the peculiar finding of a double layered patella, were recognised during childhood. cleft palate, swelling of the ear pinna, and hitch hiker thumb were absent. He was found to be homozygous, and both healthy parents heterozygous, for the R279W mutation in DTDST, and his fibroblasts showed a sulphate incorporation defect typical of DTDST disorders. Counselling was given for a recessive disorder, thereby considerably reducing the probability of affected offspring. Multiple epiphyseal dysplasia is more frequently caused by dominant mutations in the COMP (EDM1, McKusick 132400) and COL9A2 genes (EDM2, McKusick 600204). A few other patients and families with features similar to our proband have been described previously and considered to have autosomal recessive MED (EDM4, McKusick 226900). This observation confirms the existence of this entity and assigns it to the phenotypic spectrum associated with mutations at the DTDST locus.- - - - - - - - - - ranking = 1keywords = palate (Clic here for more details about this article) |
2/40. prenatal diagnosis of thoracopelvic dysplasia. A case report.BACKGROUND: Thoracopelvic dysplasia, a variant of asphyxiating thoracic dysplasia (Jeune syndrome), is an uncommon skeletal disorder characterized by a small thorax, pelvic abnormalities and other complex, combined anomalies, including hypomelia, polydactyly and renal anomalies. CASE: A 32-year-old woman, gravida 1, para 0, was referred at 27 weeks' gestation due to polyhydramnios. Sonography revealed hydramnios, low fetal thoracic circumference (TC) and abdominal circumference (AC) ratio (0.78), skull and skin edema, increased nuchal translucency (7 mm), micrognathia, low-set ears, left cardiac deviation (66 degrees), overriding fingers, and club and rock-buttock feet. amniocentesis revealed a normal karyotype (46, XY). Asphyxiating thoracic dysplasia was considered. At 40 weeks' gestation, a male infant was delivered vaginally. Besides the prenatal findings, cryptorchidism and high-arched palate were noted. radiography of the infant revealed a narrow, funnel-shaped thorax and small pelvis with short, flared iliac bones; poorly developed acetabulum; and small, shallow sciatic notch. No dyspnea was observed at five months postpartum. CONCLUSION: Thoracopelvic dysplasia should be considered when a low TC/AC ratio (< 0.8) is observed. In this case the final diagnosis was made after detailed exclusion of other disorders combined with observation of a small thorax. prenatal diagnosis of thoracopelvic dysplasia is possible.- - - - - - - - - - ranking = 1keywords = palate (Clic here for more details about this article) |
3/40. tracheomalacia in a neonate with kniest dysplasia: histopathologic and ultrastructural features.Kniest dysplasia is an autosomal-dominant chondrodysplastic condition characterized by disproportionate dwarfism, short trunk, small pelvis, kyphoscoliosis, short limbs, prominent joints, premature osteoarthritis, and craniofacial manifestations. The craniofacial abnormalities include tracheomalacia, midface hypoplasia, cleft palate, early onset myopia, retinal detachment, prominent eyes, and sensorineural hearing loss. Radiologic features include dumbbell-shaped femora, platyspondylia with anterior wedging of vertebral bodies, coronal clefts of thoracolumbar vertebral bodies, low broad ilia, and short tubular bones with broad metaphyses and deformed large epiphyses. This form of chondrodysplasia is associated with mutations in type II collagen splicing sequences. Mutations have been identified in the COL2A1 (type II collagen) gene between exons 12 and 24. Type II collagen is the predominant structural protein in cartilage, and mutations in this collagen account for the Kniest dysplasia phenotype. Histopathologic and ultrastructural features of epiphyseal plate cartilage have been described, but tracheal cartilage in an affected neonate has not been examined. The authors report the histopathologic and ultrastructural findings of anterior tracheal cartilage from a 35-day-old female with suspected chondrodysplasia who had tracheomalacia with airway obstruction. The tracheal cartilage was moderately cellular, but lacked cystic and myxoid changes in its matrix. The chondrocytes had abundant cytoplasmic PAS-positive inclusions. Some of these inclusions were diastase-resistant and were also highlighted on alcian blue staining. Ultrastructural examination revealed chondrocytes with greatly dilated rough endoplasmic reticulum containing granular proteinaceous material. There were also frequent aggregates of typical glycogen. The defect in the COL2A1 gene is secondary to mutations, especially at splice junctions, and this markedly disrupts triple helix formation. The mutated type II procollagen results in intracellular retention within the chondrocytes, as abundant granular proteinaceous material within the dilated RER. A relationship is known to exist between the proportion of mutated to normal type II collagen in the matrix and the severity of the phenotype. With low levels of normal type II collagen, the phenotypic manifestations become more severe, such as in achondrogenesis type II. Both the quantity and quality of type II collagen modulates the phenotypic expression of type II collagenopathies.- - - - - - - - - - ranking = 23.862860251948keywords = cleft palate, palate, cleft (Clic here for more details about this article) |
4/40. A man who inherited his SRY gene and Leri-Weill dyschondrosteosis from his mother and neurofibromatosis type 1 from his father.We report on a man with neurofibromatosis type 1 (NF1) and Leri-Weill dyschondrosteosis (LWD). His father had NF1. His mother had LWD plus additional findings of turner syndrome (TS): high arched palate, bicuspid aortic valve, aortic stenosis, and premature ovarian failure. The proband's karyotype was 46,X,dic(X;Y)(p22.3;p11.32). Despite having almost the same genetic constitution as 47,XXY klinefelter syndrome, he was normally virilized, although slight elevation of serum gonadotropins indicated gonadal dysfunction. His mother's karyotype was mosaic 45,X[17 cells]/46,X,dic(X;Y)(p22.3;p11.32)[3 cells].ish dic(X;Y)(DXZ1 ,DYZ1 ). The dic(X;Y) chromosome was also positive for Y markers PABY, SRY, and DYZ5, but negative for SHOX. The dic(X;Y) chromosome was also positive for X markers DXZ1 and a sequence < 300 kb from PABX, suggesting that the deletion encompassed only pseudoautosomal sequences. Replication studies indicated that the normal X and the dic(X;Y) were randomly inactivated in the proband's lymphocytes. LWD in the proband and his mother was explained by SHOX haploinsufficiency. The mother's female phenotype was most likely due to 45,X mosaicism. This family segregating Mendelian and chromosomal disorders illustrates extreme sex chromosome variation compatible with normal male and female sexual differentiation. The case also highlights the importance of karyotyping for differentiating LWD and TS, especially in patients with findings such as premature ovarian failure or aortic abnormalities not associated with isolated SHOX haploinsufficiency.- - - - - - - - - - ranking = 1keywords = palate (Clic here for more details about this article) |
5/40. Achondrogenesis type IB: agenesis of cartilage interterritorial matrix as the link between gene defect and pathological skeletal phenotype.Achondrogenesis type IB is a lethal osteochondrodysplasia caused by mutations in the diastrophic dysplasia sulfate transporter gene. How these mutations lead to the skeletal phenotype is not known. histology of plastic-embedded skeletal fetal achondrogenesis type IB samples suggested that interterritorial epiphyseal cartilage matrix was selectively missing. cartilage was organized in "chondrons" separated by cleft spaces; chondrocyte seriation, longitudinal septa, and, in turn, mineralized cartilaginous septa were absent. Agenesis of interterritorial matrix as the key histologic change was confirmed by immunohistology using specific markers of territorial and interterritorial matrix. biglycan-enriched territorial matrix was preserved; decorin-enriched interterritorial areas were absent, although immunostaining was observed within chondrocytes. Thus, in achondrogenesis type IB: (1) a complex derangement in cartilage matrix assembly lies downstream of the deficient sulfate transporter activity; (2) the severely impaired decorin deposition participates in the changes in matrix organization with lack of development of normal interterritorial matrix; and (3) this change determines the lack of the necessary structural substrate for proper endochondral bone formation and explains the severe skeletal phenotype.- - - - - - - - - - ranking = 0.67814035094906keywords = cleft (Clic here for more details about this article) |
6/40. cleft palate in spondyloepiphyseal dysplasia congenita: case reports.cleft palate is one of the common features of spondyloepiphyseal dysplasia congenita (SEDC). However, there are few clinical data about cleft palate in SEDC. We report four patients with cleft palate and SEDC including two with overt cleft palate and two with submucous cleft palate. Our results suggested that SEDC associated with cleft palate should be treated in the same way as solitary cleft palate, and submucous cleft palate may be more common in patients with SEDC than previously appreciated.- - - - - - - - - - ranking = 145.78645975694keywords = cleft palate, palate, cleft (Clic here for more details about this article) |
7/40. Molecular characterization of partial trisomy 16q24.1-qter: clinical report and review of the literature.We describe a 3(1/2)-year-old girl with psychomotor and mental retardation; dysmorphic features, including a high forehead with bitemporal narrowing; a broad nasal bridge and a broadened nose; downslanting palpebral fissures; abnormal ears; vertebral abnormalities; cardiac defect; genital hypoplasia; and anal abnormalities. The karyotype of our patient (550 bands) was normal. Molecular cytogenetic techniques, including comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH), revealed that this girl was a carrier of a de novo derivative chromosome 7 arising from a cryptic t(7;16)(p22.3;q24.1) translocation generating a trisomy 16q24.1-qter and a 7p22.3-pter deletion. FISH with a series of specific chromosome 7p and 16q probes allowed us to delineate the chromosome 7 breakpoint between YAC660G6 (WD7S517) and YAC848A12 (D7S521, D7S31, and WI-4829) and the chromosome 16 breakpoint between BAC457K7 (D42053) and BAC44201 (SGC30711). The comparison of the clinical features of our patient with those of 2 cases of pure terminal 7p deletion and 28 cases of trisomy 16q reported in the literature allowed us to establish the following phenotype-genotype correlation for trisomy of the long arm of chromosome 16: distinctive facies (high/prominent forehead, bitemporal narrowing, periorbital edema in the neonatal period); severe mental retardation; vertebral, genital, and anal abnormalities to 16q24; distal joint contractures and camptodactyly to 16q23; cleft palate and renal anomalies to 16q22; beaked nose and gall bladder agenesis to 16q21; gut malrotation; lung and liver anomalies to 16q13; and behavior abnormalities to band 16q11-q13.- - - - - - - - - - ranking = 23.184719900999keywords = cleft palate, palate, cleft (Clic here for more details about this article) |
8/40. Atelosteogenesis type II: sonographic and radiological correlation.Atelosteogenesis type II is a lethal chondrodysplasia characterized by severe micromelia, spinal abnormalities, talipes equinovarus, and abducted thumbs and toes. We present a case diagnosed at 21 weeks of gestation in which antenatal sonographic and post-mortem radiological findings were correlated. The patient had a recurrence of this disorder in a subsequent pregnancy which was terminated at 15 weeks, supporting previous reports of an autosomal recessive inheritance pattern. The feasibility of diagnosing the following morphological features by prenatal ultrasonography is demonstrated: coronal clefts of the vertebral bodies, metaphyseal and epiphyseal abnormalities, spinal deviations such as cervical kyphosis and a horizontal sacrum, additional ossification centres in the pelvis, and preaxial deviation of the thumbs and toes. The differential diagnosis of this disorder from other skeletal dysplasias with similar features is discussed.- - - - - - - - - - ranking = 0.67814035094906keywords = cleft (Clic here for more details about this article) |
9/40. Autosomal recessive multiple epiphyseal dysplasia with homozygosity for C653S in the DTDST gene: double-layer patella as a reliable sign.Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene result in a family of skeletal dysplasias, which comprise lethal (achondrogenesis type 1B and atelosteogenesis type 2) and non-lethal conditions (diastrophic dysplasia and recessive multiple epiphyseal dysplasia (rMED)). The most frequent mutation is R279W, which in a homozygous state results in rMED with bilateral clubfoot, MED, and "double layered" patella. We describe three patients with rMED caused by a previously unreported homozygous mutation in the DTDST gene. The three patients (from two families) were born to healthy, non-consanguineous parents. All developed signs of hip dysplasia in early childhood and two had episodes of recurrent patella dislocation. Two underwent bilateral total hip replacements at ages 13 and 14 years. The feet, external ears, and palate were normal. Stature was normal in all cases. Radiographs showed dysplastic femoral heads, mild generalized epiphyseal dysplasia, abnormal patella ossification, and normal hands and feet. Direct sequence analysis of genomic dna demonstrated a homozygous 1984T > A (C653S) change in the DTDST gene in all patients. The clinically normal parents were heterozygous for the change. This is the first description of a homozygous C653S mutation of the DTDST gene. hip dysplasia and patella hypermobility dominates the otherwise mild phenotype. These patients further expand the range of causative mutations in the DTD skeletal dysplasia family.- - - - - - - - - - ranking = 1keywords = palate (Clic here for more details about this article) |
10/40. cleft palate repair in spondyloepiphyseal dysplasia congenita: minimizing the risk of cervical cord compression.OBJECTIVE: Spondyloepiphyseal dysplasia congenita (SEDC) is a rare, inheritable condition that can include dwarfism, cleft palate, and C(1-2) instability. When repairing a cleft palate in a patient with SEDC, there is a significant risk of cord compression at the C(1-2) level because of neck hyperextension required for the operation. This reports presents a patient with SEDC who underwent surgery for a cleft palate, using a Ferno vacuum splint to immobilize the spine. INTERVENTION: The patient underwent general anesthesia. Good access was gained to the palate, and it was repaired without any complications. Particular attention was paid to maintaining the neck in a neutral position. CONCLUSIONS: The described technique provides the patient with the safest possible situation during anesthesia for cleft palate repair.- - - - - - - - - - ranking = 97.738879603997keywords = cleft palate, palate, cleft (Clic here for more details about this article) |
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