Temple-Baraitser Syndrome and Zimmermann-Laband Syndrome: one clinical entity?

BACKGROUND: KCNH1 encodes a voltage-gated potassium channel that is predominantly expressed in the central nervous system. Mutations in this gene were recently found to be responsible for Temple-Baraitser Syndrome (TMBTS) and Zimmermann-Laband syndrome (ZLS). METHODS: Here, we report a new case of TMBTS diagnosed in a Lebanese child. Whole genome sequencing was carried out on DNA samples of the proband and his parents to identify mutations associated with this disease. Sanger sequencing was performed to confirm the presence of detected variants. RESULTS: Whole genome sequencing revealed three missense mutations in TMBTS patient: c.1042G > A in KCNH1, c.2131 T > C in STK36, and c.726C > A in ZNF517. According to all predictors, mutation in KCNH1 is damaging de novo mutation that results in substitution of Glycine by Arginine, i.e., p.(Gly348Arg). This mutation was already reported in a patient with ZLS that could affect the connecting loop between helices S4-S5 of KCNH1 with a gain of function effect. CONCLUSIONS: Our findings demonstrate that KCNH1 mutations cause TMBTS and expand the mutational spectrum of KCNH1 in TMBTS. In addition, all cases of TMBTS were reviewed and compared to ZLS. We suggest that the two syndromes are a continuum and that the variability in the phenotypes is the result of the involvement of genetic modifiers.

[Loss of image quality due to the image output of a digital radiographic system]. / Bildqualitätseinbussen bei der Bildausgabe eines digitalen Röntgenaufnahmesystems.

Not all digital radiography systems allow an unrestricted image postprocessing for the radiologist. Depending on the X-ray system there are restrictions in varying brightness and contrast of the image. We compared grey level information that are given to the radiologist by various digital radiography systems. Histograms of differently postprocessed X-ray images were calculated, which were acquired by three different X-ray systems. We found that every modality has its own way of saving and converting the images into DICOM data. The processed image is either sent into PACS with the initial grey level range (10 or 12 bit) or the image is sent with a reduced grey level range due to windowing. The grey level range is associated with the ability of unrestricted windowing in PACS. So, taking an image with a reduced grey level range, the radiologist will face limited potential to optimise the window setting individually afterwards. The loss of image quality due to image transfer from the modality to PACS can lead to an information loss in the diagnostic relevant range.

New oral-acral syndrome with partial agenesis of the maxillary bones.

We report on a woman with congenital defect of the anterior part of the maxillary bone (including absence of incisors and canines) without cleft lip or palate, and ectrodactyly of the feet. This syndrome appears to represent a new entity of unknown cause.

Zimmermann-Laband syndrome in an adult. Long-term follow-up of a patient with vascular and cardiac complications.

Zimmermann-Laband syndrome (ZLS) is characterised by findings of coarse facial appearance, hepatosplenomegaly, and hirsutism often first observed in infancy, followed by the evolution during childhood of gingival fibromatosis, small joint hyperextensibility, and hypoplasia of the finger- and toenails. Intellectual deficit is variable. Some of these findings are suggestive of a storage disorder, but no biochemical defect has been identified. We report on a four decade follow-up of a male with ZLS who developed a cardiomyopathy and dilatation of the aortic root and arch, anomalies hitherto undescribed in this syndrome.

Unique case of growth hormone (GH) deficiency accompanied by clinical anophthalmia, hypoplastic orbits, digital dysplasia, short stature, obesity, and diabetes mellitus.

A 43-year-old female was admitted to our hospital for polydipsia and hyperglycemia. She had total blindness and globes were not recognized by inspection, indicating clinical anophthalmia. Physical examination revealed short stature, obesity, prematurely gray hair, shortness of fingers and toes, syndactyly, and multiple dental caries. Laboratory examination showed hyperglycemia, increased glycosilated hemoglobin (HbA1c) and insulin resistance on euglycemic glucose clamp. Blunted growth hormone (GH) secretion was shown in response to insulin-induced hypoglycemia, arginine infusion, and GH-releasing hormone (GHRH) loading test, and in 24 h spontaneous GH profile. Magnetic resonance imaging (MRI) and computed tomography (CT) showed dysostosis of orbit, defect of optic nerve, enlarged suprasellar cistern, and prolonged pituitary stalk. This may be the first report of a unique case with GH deficiency accompanied by clinical anophthalmia, hypoplastic orbits, digital dysplasia, short stature, obesity, and diabetes mellitus.

Oculodento-digital dysplasia: a rare syndrome.

A rare syndrome that can be diagnosed radiographically has been reviewed. A characteristic physiognomy, variable ophthalmologic anomalies and relatively specific dental and digital defects provide the diagnostic features. No hereditary component was identified and the chromosomal pattern was normal. The history, appearance and characteristic radiographic changes may, as in this case, allow the radiologist to provide a diagnosis not previously appreciated.

[Reparative giant-cell granuloma of the extremities]. / Das reparative Riesenzellgranulom der Extremitäten.

Giant-cell reparative granulomas are observed not infrequently in the mandible as sharply demarcated osteolytic lesions. On the other hand, these tumour-like lesions occurring in short tubular bones are rarely reported in the literature and, so far, only 27 cases have been described. We have records of five cases in the Westphalian Bone Tumour Register. The actual occurrence is probably greater if one assumes that the lesion is caused by an intra-osseous bleeding. This pathogenic mechanism is supported by histological evidence.

Jaw fixation as the key to diagnosis of fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva is a very rare and disabling hereditary disorder of connective tissue characterised by symmetric congenital anomalies of the great toes and thumbs and by progressive heterotopic ossification of tendons, ligaments, fasciae and striated muscles. In this case we report a 17-year-old boy who presented with a painful swelling of the right mandibula with trismus. Multiple heterotopic soft tissue calcifications, severe scoliosis and typical anomalies of toes and thumbs on the radiographs were pathognomonic for fibrodysplasia ossificans progressiva.

Effect of pregnancy on the lamina dura.

Serum chemistry studies and radiological examination of the lamina dura and phalanges were conducted in 50 pregnant women, 25 of whom had been administered calcium and vitamin D supplements during the 3rd trimester. The non-supplemented pregnant women showed significant hypocalcaemia, elevated serum heat-labile alkaline phosphatase activity, and resorption of the lamina dura. The supplemented group of pregnant women also showed resorption of the lamina dura, although the serum chemistry was essentially normal. It is suggested that, probably because of gestational hyperparathyroidism, mild resorption of the lamina dura may be a feature of normal pregnancy.

Hard palate mucosal grafts for defects of the nail bed.

The authors present 2 children in whom a hard palate mucosal graft was used for a defect of the nail bed after resecting subungual exostosis. After the tumor was resected with the overriding nail bed, hard palate mucosa without periosteum was grafted to the nail bed defect. In both patients the graft took completely, and within 2 weeks after the operation the patients were able to enjoy activities of daily life, including athletic movement, without any symptoms. Nail growth was uneventful and was complete in 4 or 5 months after the operation without any complications. The authors think that a hard palate mucosal graft is a valid choice for a defect of the nail bed, and the mucosa does not need to be harvested with periosteum. The grafting of hard palate mucosa without periosteum to a defect of the nail bed contributes to a shorter healing time, resulting in a reduction in the period of restriction of movement in activities of daily life, and this is a great advantage in children.

The Zimmermann-Laband syndrome. / Das Syndrom von Zimmermann-Laband.

We report on two patients who exhibit the typical features of the rare Zimmermann-Laband syndrome such as gingival fibromatosis, swelling of perioral tissues, nail hypo/aplasia, and abnormalities of terminal phalanges. The older patient suffers from epileptic seizures and shows osseous mandibular hypertrophy, two maxillary mesiodentes and lumbar spondylodysplasia. In the 2nd patient, a 3 year old male, the characteristic morphological features are already present.

Flexible hinge toe implant arthroplasty for rheumatoid arthritis of the first metatarsophalangeal joint: long-term results.

We report the long-term clinical results and survival rate of the implant in flexible hinge toe implant arthroplasty of the first metatarsophalangeal joint, combined with a shortening oblique osteotomy of the metatarsal neck in the lateral toes, in patients with rheumatoid arthritis. Between 1983 and 1990, arthroplasty was performed on 97 feet in 66 patients. Twenty-seven patients died; follow-up information was available for 60 feet in the remaining 39 patients, who were followed for an average of 12 years. Twenty-nine patients (74%) were satisfied with the outcome after surgery, 7 were satisfied but had some pain or recurrent deformities, and 3 were unsatisfied. Radiologically, visible fracture was identified in nine implants. Four implants were removed because of infection (n = 2) or recurrent deformity (n = 2); no implant was removed because silicone synovitis developed. With revision as the endpoint, the implant survival rate was 93% at 10 years, and with radiographic implant fracture as the endpoint, the implant survival rate was 87% at 10 years. Shortening oblique osteotomy of the lateral toes appeared to decrease the rate of implant fracture and should be performed concomitantly with implantation when rheumatoid forefoot deformities are being reconstructed.

Fibrodysplasia (myositis) ossificans progressiva. Clinical lessons from a rare disease.

Fibrodysplasia (myositis) ossificans progressiva is a rare dominantly inherited disorder, in which defects in skeletal patterning particularly affecting the big toes, are associated with progressive endochondral ossification of the large striated muscles in a specific order leading to prolonged disability. A recent series of 28 patients studied for as many as 24 years exemplifies the presentation and course of this disease. Painful swelling of muscles (myositis) leading to ossification began at a mean age of 4.6 years (range, 0-16 years) initially in the neck and upper spine (in 25 subjects) and later around the hips, other major joints, and jaw. The rate and extent of disability was unrelated to the time of onset. No form of treatment produced consistent benefit. Despite the unique clinical features, the initial diagnosis of fibrodysplasia ossificans progressiva was often wrong and usually considerably delayed. Mistaken histologic diagnoses such as soft tissue sarcoma or fibromatosis could lead to inappropriate treatment.

[Combination of rare anomalies of the cervical spine and peripheral skeleton]. / Kombination seltener Anomalien der Halswirbelsäule und des peripheren Skeletts.

This paper presents a case report on a 59-year old patient of small stature with moderate mental retardation, strabismus and several rare skeletal anomalies. We found an os odontoideum, a dysontogenetic 3fold fusion of cervical vertebrae, multiple double-sided wrist bone dysplasias and brachytelephalangical digiti pedis I, but no anomalies of the heart or genitals. Clinical signs, biochemical parameters and results of x-ray and ultrasonic examination are demonstrated in this complex malformation syndrome that combines different anomalies known from other syndromes.