Tricorhinophalangeal Syndrome type 1: a novel variant and Perthes-like hip changes as first manifestation.

We report a case of Trichorhinophalangeal syndrome type I (TRPS1) in a 16-year-old boy who was referred due to painless finger deformities over the last year. Legg-Calvé-Perthes disease (LGP) had been diagnosed at age 7 and required surgical treatment at age 12. Parents were healthy and non consanguineous; there was family history of pectus carinatum of maternal lineage. On examination the patient presented a bulbous nose, thin and sparse scalp hair; pectus carinatum; clinodactyly of the first and fifth fingers and hard painless swelling of all of the proximal interphalangeal joints; brachydactyly of the toes. Laboratory tests were unremarkable and radiographic studies revealed distinctive abnormalities of the hands (e.g., epiphyseal coning). This diagnosis was confirmed by gene sequencing, which identified in heterozygosity a pathogenic variant c.124G>T (p.Glu42Ter) in the exon 3 of the TRPS1 gene. The diagnosis of TRPS1 may be suspected upon identification of characteristic physical features, a compatible clinical history and imaging findings.

Non-ossifying fibroma with a pathologic fracture in a 12-year-old girl with tricho-rhino-phalangeal syndrome: a case report.

BACKGROUND: Tricho-rhino-phalangeal syndrome (TRPS) is a rare autosomal dominant genetic disorder characterized by distinctive craniofacial and skeletal abnormalities, while non-ossifying fibroma (NOF) is a common benign bone tumour in children and adolescents. To date, no case of TRPS coexisting with NOF has been reported. This report presents a 12-year-old girl who had the characteristic features of tricho-rhino-phalangeal syndrome and non-ossifying fibroma with a fibula fracture. CASE PRESENTATION: A 12-year-old girl was admitted to the Department of Endocrinology and Diabetes for evaluation of brachydactyly and a right fibula fracture. Clinical examination revealed sparse scalp hair, a characteristic bulbous pear-shaped nose, and brachydactyly with significant shortening of the fourth metatarsal. Neither intellectual disability nor multiple exostoses were observed. Radiography of both hands showed brachydactyly and cone-shaped epiphyses of the middle phalanges of the digits of both hands with deviation of the phalangeal axis. Genetic analysis of TRPS1 identified a heterozygous germline sequence variant (p.Ala932Thr) in exon 6 in the girl and her father. Approximately 1 month before being admitted to our department, the girl experienced a minor fall and suffered a fracture of the proximal fibula in the right lower limb. The pathological cytological diagnosis of the osteolytic lesion was NOF. Ten months following the surgery, the lesion on the proximal fibula of the girl disappeared. CONCLUSIONS: In conclusion, the present study is the first to report a rare case of NOF with a pathologic fracture in the fibula of a girl with TRPS. The identification of a missense mutation, (p.Ala932Thr), in exon 6 of TRPS1 in this kindred further suggested that the patient had type I TRPS and indicated that mutations in this exon may be correlated with more pronounced features of the syndrome. Radiological techniques and genetic analysis played key roles in the definitive diagnosis.

Multiple long bone cysts revealed by MRI in trichorhinophalangeal syndrome type II predisposing to pathological fractures.

Trichorhinophalangeal syndrome type II is a rare genetic disorder with the few published case reports mainly reporting the radiographic skeletal manifestations. There are no published imaging reports of long bone cysts involving multiple bones in this condition. We report a unique case of bone cysts involving multiple long bones detected with MRI in a patient with trichorhinophalangeal syndrome type II complicated by a subsequent pathological fracture. It is possible that the bone cysts are a previously undescribed feature of this syndrome; however, the evidence is insufficient to establish a definite association. Chromosomal abnormality identified in this patient is consistent with trichorhinophalangeal syndrome type II with no unusual features. Although the nature of these bone cysts is unclear, they are one of the causes of the known increased fracture risk observed in this syndrome.

Crooked fingers and sparse hair: an interesting case of trichorhinophalangeal syndrome type 1.

Trichorhinophalangeal syndrome type 1 is a rare skeletal dysplasia of autosomal-dominant inheritance due to defects in the TRPS-1 gene. The syndrome is characterised by sparse slow-growing hair, a bulbous pear-shaped nose, cone-shaped epiphyses and deformities of the interphalangeal joints resembling those in rheumatoid arthritis. We present a case of trichorhinophalangeal syndrome in a 23-year-old man who presented with symmetrical painless progressive deformity of the fingers in both hands.

Langer-Giedion syndrome associated with congenital dural arterio-venous fistula.

Langer-Giedion syndrome (LGS) is a rare disease caused by deletion of chromosome 8q23.3-q24.11. Clinical manifestations include among others multiple exostoses, short stature, intellectual disability, and typical facial dysmorphism. Dural arterio-venous shunts (DAVS) in the pediatric age are rare lesions, which have been classified into three types: dural sinus malformations (DSM), infantile type DAVS (IDAVS), and adult type DAVS (ADAVS). We report a case of a patient with a known LGS who was diagnosed with complex intracranial dural AV fistula at the age of 20. An association between LGS and intracranial dural AV fistulas has to our knowledge never been reported before.

Prenatal diagnosis of Langer-Giedion Syndrome confirmed by BACs-on-Beads technique.

Langer-Giedion Syndrome (LGS), with characteristic phenotypic features including craniofacial dysmorphic signs, postnatal growth retardation and skeletal abnormalities, mental impairment, urogenital malformations and heart defects, is caused by partial deletions of the long arm of chromosome 8. We present a case of a female fetus with LGS. The diagnosis was molecularly proven with the BACs on Beads method at 32 weeks of gestation. To the best of our knowledge, prenatal recognition of that genetic defect had previously been made in only one case. Also, it has never been described before.

Langer-Giedion syndrome: the evolving imaging features in hands and beyond.

Trichorhinophalangeal syndrome (TRP) is a group of rare genetic disorders with characteristic clinical and radiological features. In this case report we discuss the evolution of imaging features in hands in a Chinese boy diagnosed with TRP II (Langer-Giedion syndrome, LGS). This article ramifies the diagnostic value of serial hand radiograph in clinically suspected cases of TRP.

An interstitial, apparently-balanced chromosomal insertion in the etiology of Langer-Giedion syndrome in an Asian family.

Langer-Giedion syndrome (LGS; MIM 150230), also called trichorhinophalangeal syndrome type II (TRPS2), is a contiguous gene syndrome caused by a one-copy deletion in the chromosome 8q23-q24 region, spanning the genes TRPS1 and EXT1. We identified an LGS family with two affected and two unaffected siblings from unaffected parents. To investigate the etiology of recurrence of LGS in this family, array CGH was performed on all family members. We identified a 7.29 Mb interstitial deletion at chromosome region 8q23-q24 in the two affected siblings, but no such deletion in the unaffected family members. However, the mother and one of the two unaffected siblings carried a 1.29 Mb deletion at chromosome region 8q24.1, sharing the distal breakpoint with the larger deleted segment found in the affected siblings. Another unaffected sibling had a 6.0 Mb duplication, sharing the proximal breakpoint of the deletion in the affected siblings. Karyotypic and FISH analyses in the unaffected mother revealed an insertional translocation of 8q23-q24 genomic material into chromosome 13: 46,XX,ins(13;8)(q33;q23q24). This insertional translocation in the mother results in the recurrence of LGS in this family, highlighting the importance of submicroscopic rearrangements in the genetic counseling for LGS.

The use of cone beam computed tomography for the assessment of trichorhinophalangeal syndrome, type I - a case report.

Trichorhinophalangeal syndrome type I is a rare autosomal dominant disorder characterized by cone-shaped epiphysis, sparse fine hair, pear-shaped nose and variable growth retardation. The typical craniofacial features include thin upper lip, elongated philtrum, large outstanding ears, shortened posterior facial height associated with short mandibular ramus and reduced and superiorly deflected posterior cranial base. This report describes a 17-year-old male patient with trichorhinophalangeal syndrome type I and a detailed description of the craniofacial radiographic findings, including the use of cone beam computed tomography images for determination of the airway and temporomandibular joint discrepancies.

Clinical, biochemical, and genetic analysis of two korean patients with trichorhinophalangeal syndrome type I and growth hormone deficiency.

Tricho-rhino-phalangeal syndrome type I (TRPSI) is a rare autosomal dominant hereditary disorder characterized by sparse hair, bulbous nose, long philtrum, thin upper lip, and skeletal abnormalities including cone-shaped epiphyses, shortening of the phalanges, and short stature. TRPSI is caused by mutations in the TRPS1 gene. Herein, we report two Korean cases of TRPSI. Although both patients (a 17-year-old-female and a 14-year-old male) had typical clinical findings, Patient 1 had an additional growth hormone (GH) deficiency. Treatment with recombinant human growth hormone (rhGH) 0.7 IU/kg/week led to an increase in growth velocity. Over 10 years of GH therapy, the mean growth velocity was 5.7 ± 0.9 cm/year. However, the patient 2 did not show apparent GH deficiency by GH stimulation test, had a poor response with rhGH therapy and GH therapy was discontinued after 6 months. Upon genetic analysis of the TRPS1 gene, two mutations were found. Patient 1 had a heterozygous mutation c.2520dupT (p.Arg841LysfsX3) which had not been previously reported. Patient 2 had a known nonsense mutation c.1630C>T (p.Arg544X). In summary, we were the first to report Korean patients with mutation of TRPS1.

Further case of microdeletion of 8q24 with phenotype overlapping Langer-Giedion without TRPS1 deletion.

Langer-Giedion syndrome results from a microdeletion at 8q24.1 encompassing the EXT1 and the adjacent TRPS1 gene. We report on a boy with an oligo array-cgh characterized small microdeletion involving EXT1 alone but with some features of Langer-Giedion syndrome suggesting a functional disturbance of TRPS1. This boy, in addition to a mild Langer-Giedion like phenotype, also had some unusual features including prominent toe pads and fat pads on the soles of his feet similar to those described in Pierpont syndrome.

Clinical and intraoral findings of a patient with tricho-rhino-phalangeal syndrome type I.

Tricho-rhino-phalangeal syndrome (TRPS) is a rare and an autosomal dominant disorder having the following characteristics: slowly growing sparse hair, medially thick and laterally thin eyebrows, bulbous tip of the nose, long flat philtrum and thin upper lip with vermilion border, protruding ears, cone-shaped epiphyses and swelling. Our report intends to introduce TRPS to the dental literature and to present oral, clinical and radiological data of a patient with TRPS. A rare association of supernumerary teeth was also diagnosed and one of them was extracted as it impeded on the eruption path of left premolar tooth.

Tetraparesis due to exostotic osteochondroma at upper cervical cord in a patient with multiple exostoses-mental retardation syndrome (Langer-Giedion syndrome).

STUDY DESIGN: Case report of a severe upper cervical cord compression and tetraparesis by a massive cervical exostotic osteochondroma in a patient with multiple exostoses-mental retardation syndrome (Langer-Giedion syndrome; LGS). OBJECTIVE: To describe this very rare pathological condition and the results of surgical intervention. SETTING: Gifu, Japan. METHODS: A 23-year-old man was referred to our clinic because of progressing tetraparesis. He had previously been diagnosed with hereditary multiple exostoses and mental retardation. As he had not complained of any symptoms, his family only noticed the tetraparesis after advanced deterioration. His face possessed the pathognomic features of LGS. A postmyelogram CT scan demonstrated an exostotic mass arising from the left-side C2 pedicle with associated severe spinal cord compression. He was diagnosed with LGS. Hemilaminectomy on the left side and resection of the osteochondroma were performed. RESULTS: At 5 years postoperatively, a neurological examination showed the full return of all motor functions. The CT scan revealed no intracanalar recurrence of the tumor. CONCLUSION: In this case of severe tetraparesis due to cervical osteochondroma, decompression by hemilaminectomy provided excellent results. In patients with LGS and intracanalar osteochondroma, the neurological deficit may be masked by mental retardation. Hence, awareness of this pathological condition will help clinicians diagnose it at an early stage.

[Surgical therapy of cone-shaped epiphyses of the proximal interphalangeal joints in tricho-rhino-phalangeal syndrome type I: a survey among three successive generations of a single family]. / Chirurgische Therapie der Zapfenepiphysen an den proximalen Interphalangealgelenken beim Tricho-Rhino-Phalangealen Syndrom (TRPS) Typ I: Eine Familenübersicht anhand von drei Generationen.

Report on 6 individuals, occurring in three successive generations of a single family, who were affected by "classical" tricho-rhino-phalangeal syndrome type I. Besides pear-shaped noses, enlarged philtrum, hypotrichosis, premature alopecia, coned epiphysis at the proximal interphaleangeal joints with consecutive ulnar deviation of the long fingers, dysostotic feet, Perthes-like hip dysplasia with multilocated joint laxity and hyposomia were impressing. Height was 168 cm, corresponding to the 50 (th) percentile. Radiographs and 3D-reconstruction of both hands showed asymmetrical brachymetacarpia, brachymesophalangia and painful invaginations of the middle phalanx bases (type 12 according to Giedion). Angular deformities are seen predominantly in the index finger decreasing to the ring finger. Painful cone-shaped epiphyses with ulnar dislocation of the PIP joints were stabilized following resection arthrodesis with tension band osteosynthesis. At reexamination 48 months postoperatively a painfree and powerful pinch grip function of both hands was restored. All family members who showed the phenotypical features of TRPS type I revealed in genetic analysis also identical mutations. Inside the exon 4 in position 1831 there was a nonsens mutation C --> T. Non-afflicted relatives did not show this mutation.

[Orthopedic considerations of trichorhinophalangeal syndrome type II]. / Orthopädische Aspekte des Trichorhinophalangealen Syndroms Typ II.

INTRODUCTION: The trichorhinophalangeal syndrome type II or Langer-Giedion syndrome is regarded as a rare abnormity that is marked by a number of clinical characteristics beside multiple cartilaginous exostoses. RESULTS: The deviation of the fingers within the scope of the TRPS II that is often reported in literature can not be found in the case at issue of a now 14 year old boy. The course of disease was complicated due to consecutive axis deviation of two large joints of the lower extremities being determined by the syndrome. Due to the marked exostoses in the area of the growth plate of the left knee joint a valgus deformity developed there. It was corrected with means of a temporary clamping of the growth plate. With the increasing valgus deformity of the right ankle causing a calcaneovalgus foot deformity the osteochondroma located at the distal fibula was also removed and a temporary clamping of the growth plate was carried out at the right medial malleolus. From earliest childhood repeating cartilaginous exostoses both at the extremities and the trunk attracted attention. Also strongly developed are the facial distinguishing marks which determine the typical shape of the face. CONCLUSION: By the case of a now 14 year old boy with severe orthopedic complications considerations are made concerning therapeutic principles due to the TRPS II.

Clinical characteristics of tricho-rhino-phalangeal syndrome type I in Taiwanese.

Tricho-rhino-phalangeal syndrome type I (TRPS-I) is a malformation syndrome characterized by distinctive craniofacial and skeletal abnormalities. Only one case of TRPS-I has been previously reported in Taiwan. This retrospective study analyzed the clinical, roentgenographic, and histopathologic findings in seven patients with a diagnosis of TRPS-I who were treated at a hospital in Tainan during a 6-year period from 1994 to 1999. Physical examination revealed fine, sparse, and short scalp hair, a pear-shaped nose, long philtrum, thinning of the lateral portion of the eyebrows, and brachydactyly of the thumbs and big toes. The stature and intelligence of these patients were normal. Histopathologic examination of the scalp in two patients showed hypotrichosis without inflammation or scarring. Roentgenographic evaluation of both hands and feet showed cone-shaped proximal epiphyses of the middle phalanges in all patients. The findings of this report suggest that TRPS-I is not rare among Taiwanese, although the island-wide incidence is not known. The diagnosis of this syndrome in our department was greatly facilitated by our prior experience with treatment of the first patient in this series because TRPS-I is readily recognizable by its characteristic clinical and roentgenographic features. The identification of these features is important to the facilitation of genetic and cosmetic counseling. In addition to the typical craniofacial manifestations, all patients in this study showed brachydactyly of the big toes. This additional feature appears to offer an easy way to recognize the syndrome clinically.

[Trichorhinophalangeal syndrome. Case report and biophysical study of hair shaft parameters]. / Das Trichorhinophalangealsyndrom. Fallbeispiel mit untersuchung der biophysikalischen Haarschaftparameter.

In 1956 Klingmüller first described the trichorhinophalangeal syndrome (TRPS), which was named by Giedion ten years later. The syndrome includes a combination of typical hair, facial and bone abnormalities with variable expression allowing the further distinction of three subtypes. In a 37-year old patient with TRPS type I who reportedly had reduced hair growth length, clinically fine and brittle hair were found. Scanning electron microscopy revealed widely spaced cuticular scales. Quantitative measurement of the biomechanical properties of the hair showed a significant increase in the viscous parameter. This could be a result of decreased disulfide bridges and increased halogen bonds in the keratin matrix of the hair. In dermatological practice patients with TRPS often present because of hair abnormalities. Because of premature arthrosis due to skeletal abnormalities, occupational counseling is advised.Congenital heart problems, kidney abnormalities and endocrinological problems are rare, but should be sought in the symptomatic individual. Apart from mild hair care and avoidance of additional physical or chemical injuries due to hair cosmetic procedures,there is no treatment for the hair defects.

Abnormal modelling of the humeral head in the tricho-rhino-phalangeal syndrome: a new radiological observation.

The case of a 27-year-old female patient with tricho-rhino-phalangeal (TRP) type I syndrome is reported. The patient demonstrated the classical features of slowly growing hair, a bulbous nose and brachydactyly with swelling at the interphalangeal joints, but in addition showed some of the less common manifestations such as supernumerary teeth and prognathism. To the authors' knowledge this is the first reported case in which modelling abnormalities of the proximal humerus mirror those seen in the femoral head. This adds weight to the argument that the skeletal abnormalities in TRP are part of a generalized bone dysplasia.