Child ; Female ; Humans ; Langer-Giedion Syndrome ; diagnosis

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.
Adolescent ; DNA-Binding Proteins ; genetics ; Humans ; Langer-Giedion Syndrome ; genetics ; Male ; Mutation ; Osteoporosis ; genetics ; Transcription Factors ; genetics

Langer-Giedion syndrome is a very rare genetic disorder that is caused by the deletion on chromosome 8q24.1, encompassing the TRPS1 and EXT1 genes. We describe a 5-month-old female patient who was admitted to our hospital with clinodactyly and weakness in both thumbs. The patient's karyotype was 46,XX,der(4)t(4;19)(q27;q11),der(8)t(4;8)(q27;q22.3),der(19)t(8;19)(q22.3;q11)del(8)(q23q24.1). Multiplex ligation-dependent probe amplification (MLPA) analysis showed that the patient had a heterozygous deletion, rsa 8q24(P064)x1 and rsa 8q24(P245)x1. Array comparative genomic hybridization (CGH) analysis further revealed three interstitial deletions spanning a total of 13.7 Mb at 8q23.1–q24.13. Based on clinical findings and confirmation by cytogenetic, MLPA, and array CGH analyses, the patient was diagnosed with sporadic Langer-Giedion syndrome with three-way translocations. This is the first case of Langer-Giedion syndrome with complex chromosomal rearrangements in Korea.
Comparative Genomic Hybridization ; Cytogenetics ; Female ; Humans ; Infant ; Karyotype ; Korea ; Langer-Giedion Syndrome ; Multiplex Polymerase Chain Reaction ; Thumb

Lange-Giedion syndrome, or trichorhinophalangeal syndrome type 2 (TRPSII), is a clinical syndrome characterized by mild growth restriction, mental retardation, microcephaly and dysmorphic face. Bulbous nose, large protruding ears and loose redundant skin are distinguishing features, as well as lax joints and phalangeal abnormalities of the hands and multiple exostoses. TRPS1 and EXT1 gene deletion are responsible for this. Diagnosis is mainly based on clinical and radiographic features. In Korea, no cases of this disease have been reported thus far. Along with a review of the literature, we report a case of TRPSII in a neonate who had peculiar face representing TRPSII, polydactyly, Mullerian duct cyst, and ptosis and was found to have an interstitial deletion of 8q23-24.1.
Diagnosis ; Ear ; Exostoses, Multiple Hereditary ; Gene Deletion ; Hand ; Humans ; Infant, Newborn ; Intellectual Disability ; Joints ; Korea ; Langer-Giedion Syndrome* ; Microcephaly ; Nose ; Polydactyly ; Skin

OBJECTIVE: To explore the genetic etiology of a pedigree affected with tricho-rhino-phalangeal syndrome. METHODS: Next-generation sequencing (NGS) using a gene panel for hereditary osteopathies was carried out for the proband. Suspected mutation was validated in the proband and her parents by Sanger sequencing. RESULTS: A heterozygous frameshift variation c.1995dupA (p.Gly666Argfs*20) of the TRPS1 gene was detected in the proband but not in her parents. CONCLUSION The novel c.1995dupA (p.Gly666Argfs*20) mutation of the TRPS1 gene probably underlies the disease in the proband.
DNA-Binding Proteins ; genetics ; Female ; Fingers ; abnormalities ; Frameshift Mutation ; Hair Diseases ; genetics ; Humans ; Langer-Giedion Syndrome ; genetics ; Nose ; abnormalities ; Pedigree ; Transcription Factors ; genetics