Am J Med Genet A. 2012 Mar; 158A(3): 659-63
Pereza N, Severinski S, Ostojić S, Volk M, Maver A, Dekanić KB, Kapović M, Peterlin B

Langer-Giedion syndrome (LGS) is a contiguous gene syndrome caused by a hemizygous deletion on chromosome 8q23.3-q24.11 involving TRPS1 and EXT1 genes. We report on a girl with LGS phenotype and a 7.5 Mb interstitial deletion at chromosome 8q23.3-q24.13. Array-comparative genomic hybridization (a-CGH) revealed a deletion encompassing only the EXT1 and not the TRPS1 gene. Even though the deletion of TRPS1 and EXT1 genes is responsible for craniofacial and skeletal features of LGS, there have been previous reports of patients with LGS phenotype and 8q24 deletions leaving the TRPS1 gene intact. To our knowledge, this is the third such case. Our patient differs from previously reported LGS patients without TRPS1 gene deletion in that she has the typical LGS facial dysmorphism and skeletal abnormalities. However, the girl is of normal height and has only a mild developmental delay. Additionally, she has dyslalia and premature adrenarche classified as Tanner stage 3 premature pubarche which have not yet been described as features of LGS. We examine the molecular breakpoints and phenotypes of our patient and previously reported cases. © 2012 Wiley Periodicals, Inc.

Am J Med Genet A. 2011 Nov; 155A(11): 2784-7
Carvalho DR, Santos SC, Oliveira MD, Speck-Martins CE

Langer-Giedion syndrome (LGS) (OMIM 150230) is defined as a contiguous gene syndrome caused by loss of functional copies of the TRPS1 and EXT1 genes usually secondary to 8q microdeletion. Tibial hemimelia (TH) is the least common lower limb deficiency characterized by hypoplasia of the tibia with relatively intact fibula. We describe the third report of LGS with bilateral TH and an 8q23.1-q24.12 interstitial deletion. It is not possible to exclude that this association is fortuitous, but our report reinforces the suggestion of a putative gene involved in limb development in this chromosomal region interval.

Tidsskr Nor Laegeforen. 2011 Aug 9; 131(15): 1420-3
Brodwall KM, Júlíusson PB, Bjerknes R, Hovland R, Fiskerstrand T

The trichorhinophalangeal syndrome (TRPS) is a hereditary, skeletal dysplasia which has a characteristic clinical presentation and is classified in types 1, 2 and 3, based on phenotype and genotype. Typical findings may be mild and many patients probably remain undiagnosed.The paper is based on four case reports and provides a short review of the condition.Our four patients all have typical facial features, such as a large nose and thin upper lip, thin hair and short curved fingers with characteristic radiological findings. The condition is autosomal dominant and caused by a mutation in the TRPS1 gene, which codes a gene-regulating protein involved in development of hair and modulation of chondrocytes. The diagnosis can be based on clinical findings, but DNA-analysis can be of help in unclear situations. Two of our patients were diagnosed from clinical and radiological findings, but for the two others genetic examinations were done as well. There is no causal treatment, but the diagnosis can give patients an explanation of their problems, and genetic counseling for the patient and family can be offered. Orthopedic surgery and cosmetic aids are valuable for many.In an increasingly technified medical daily life, the clinical view is still the most important tool in diagnosing patients with this condition.

Chin Med J (Engl). 2011 May; 124(10): 1583-5
Shao C, Tian J, Shi DH, Yu CX, Xu C, Wang LC, Gao L, Zhao JJ

Tricho-rhino-phalangeal syndrome (TRPS) was first reported in 1966. Although mutation of TRPS1 gene is considered to be responsible for the syndromes in 2000, investigation of bone metabolism and changes of serum insulin-like growth factor (IGF)-1 level in this kind of patients is rare. Here, we report a patient with TRPS I (MIM 190350) presenting a novel mutation (1096insA) and abnormal changes of severe osteoporosis as well as low serum IGF-I level.

World J Pediatr. 2011 May; 7(2): 111-7
Bennàssar A, Ferrando J, Grimalt R

Alopecia present from birth includes a broad differential diagnosis and often represents a diagnostic and therapeutic challenge for the involved physician.An initial correct diagnosis and classification is essential because structural hair defects may be the expression of a genetic disorder affecting hair growth, part of a congenital syndrome with accompanying hair malformations, or a marker for an underlying metabolic disorder and may impact the mental and physical development of a child. Pathological hair loss rarely occurs in the first year of life; however, it may be a leading symptom of many congenital diseases.In recent years, the clinical and microscopic features of hereditary hair shaft disorders have been characterized and classified. Furthermore, significant progress has been made in our knowledge of genes that control the normal development and differentiation of hair follicles, and thus the research is to define and classify the hair disorders within a genetic basis.In this article we discuss several types of genotrichosis and provide a practical classification based on their clinical features.

Eur J Med Genet. 2011 Jul-Aug; 54(4): e405-8
Rué M, Lüdecke HJ, Sibon I, Richez C, Taine L, Foubert-Samier A, Arveiler B, Schaeverbeke T, Lacombe D, Tison F, Goizet C

Sparse scalp hair, a peculiar shape of the nose, and cone-shaped epiphyses of the phalanges are the hallmarks of the tricho-rhino-phalangeal syndromes (TRPS). Short stature, hip dysplasia, and malformations of inner organs including mitral valve prolpase have also often been described for these conditions. Here, we described a 64-year-old woman with molecularly proved TRPS I and several atypical late-onset rheumatologic and neurological symptoms.

Clin Dysmorphol. 2011 Apr; 20(2): 121-6
Berger M, Rost I, Schmidt H

Am J Med Genet A. 2010 Aug; 152A(8): 2115-9
Izumi K, Takagi M, Parikh AS, Hahn A, Miskovsky SN, Nishimura G, Torii C, Kosaki K, Hasegawa T, Neilson DE

Clin Genet. 2010 Dec; 78(6): 591-3
Sarafoglou K, Moassesfar S, Miller BS

Br J Dermatol. 2010 Aug; 163(2): 416-9
Chen LH, Ning CC, Chao SC

The trichorhinophalangeal syndromes (TRPSs) are rare hereditary diseases with mainly autosomal dominant inheritance. Three different forms sharing similar clinical features with heterogeneous mutations have been identified: type I (TRPS I), type II (TRPS II) and type III (TRPS III). These syndromes have characteristic facial abnormalities such as sparse and slow-growing scalp hair, laterally sparse eyebrows, bulbous pear-shaped nose, elongated and flat philtrum, thin upper lip, and protruding ears. Various skeletal abnormalities are also frequently noted: short stature, shortening of the phalanges and metacarpals, cone-shaped epiphyses and Perthes-like change of the hips.(1-4) The TRPS1 gene was first identified in 2000 and mapped to 8q24.1.(1) More than 50 mutations have been found in the gene to date. We here report mutation analysis of eight patients with the typical phenotype of TRPS I, revealing five novel mutations.

Clin Dysmorphol. 2010 Apr; 19(2): 98-100
Al-Dosari MS, Alkuraya FS

J Clin Endocrinol Metab. 2009 Dec; 94(12): 5028-33
Shah BC, Moran ES, Zinn AR, Pappas JG

Homozygous mutation of the short stature homeobox-containing gene, SHOX, results in Langer mesomelic dysplasia (LMD). Our case presented with severe short stature and skeletal deformities with Turner syndrome (TS) and a SHOX gene abnormality due to a downstream allele deletion in her normal X chromosome. Medical literature review did not reveal similar cases that were treated with GH therapy.We present an 11-yr-old with combined TS and LMD with severe short stature and skeletal deformities. She was studied for the effect of GH therapy on stature and skeletal deformities. Karyotype testing showed 45,X/46,X,idic(X). Genetic analysis of SHOX gene testing did not detect any exonic mutations. Interestingly, both alleles of the flanking marker DXYS233, a marker downstream of the 3' end of SHOX coding sequence, were absent with resultant LMD. GH therapy in the mean dose of 0.321 mg/kg/wk was administered for 4 yr (0.287, 0.355, 0.317, and 0.327 mg/kg/week in the first, second, third, and fourth years, respectively). Clinical data were reviewed.The growth rates of 3.46, 3.87, 2.3, and 0.7 cm/yr were observed in the first, second, third, and fourth years of the GH therapy, respectively. There was no clinical deterioration of the skeletal deformities.There was a failure to achieve growth improvements with GH therapy for 4 years, but there was no worsening of the skeletal deformities. We conclude that GH therapy may not be beneficial in severe short stature due to combined TS and LMD resulting from homozygous SHOX deficiency.