Child, Preschool ; Facial Asymmetry ; congenital ; pathology ; Growth Disorders ; congenital ; pathology ; Humans ; Hypertrophy ; congenital ; Infant ; Male

Cockayne syndrome is a rare autosomal recessive disorder of childhood characterized by cachectic dwarfism with senile-like appearance, mental retardation, photosensitive dermatitis, loss of adipose tissue, pigmentary degeneration of retina, microcephaly, deafness, skeletal and neurologic abnormalities. We describe here an 18 year old boy with Cockayne syndrome who had, in addition to the typical features of the disorder, fasting hyperinsulinemia and growth hormone deficiency.
Adolescent ; C-Peptide/blood ; Cockayne Syndrome/*complications/pathology ; Growth Disorders/*complications/pathology ; Growth Hormone/*deficiency ; Humans ; Hyperinsulinism/*complications/pathology ; Insulin/blood ; Male ; Optic Atrophy/pathology ; Retinal Degeneration/pathology

Animals ; Eosinophilia ; genetics ; pathology ; Gene Rearrangement ; Humans ; Lymphoma ; genetics ; pathology ; Myeloproliferative Disorders ; genetics ; pathology ; Receptor, Fibroblast Growth Factor, Type 1 ; genetics ; Receptor, Platelet-Derived Growth Factor alpha ; genetics ; Receptor, Platelet-Derived Growth Factor beta ; genetics

Anterior disc displacement is a common subtype seen in temporomandibular disorders (TMD) patients. It may cause mandibular movement disorders, such as clicking of joint, intermittent closed lock, limitation of mouth opening, etc. These disorders may affect the life qualities of patients. Anterior disc displacement may also cause mandibular malformations, especially among adolescents, which may affect the growth of condyle, therefore may have a correlation with mandibular retrusion or mandibular deviation when grown up. This paper going to review the influences of anterior disc displacement on oral mandibular function and morphology and their biological mechanisms.
Adolescent ; Humans ; Mandible ; abnormalities ; pathology ; Mandibular Condyle ; growth & development ; Mandibular Diseases ; etiology ; Movement ; Retrognathia ; etiology ; Temporomandibular Joint Disorders ; etiology ; physiopathology

The 8p11 myeloproliferative syndrome (EMS) is named as stem cell leukemia/lymphoma syndrome, and is an aggressive neoplasm associated with chromosomal translocations involving the fibroblast growth factor receptor 1 (FGFR1) tyrosine kinase gene on chromosome 8p11-12. EMS is a syndrome characterized by peripheral blood leucocytosis with eosinophilia, myeloid hyperplasia of bone marrow, and T-cell lymphoblastic leukemia/lymphoma. Clinically, EMS is an aggressive disease with a short chronic phase before rapid transformation into acute leukemia. Its prognosis is poor. The only curative option for patients with EMS at this time appears to be bone marrow or stem cell transplantation. At the molecular level, all cases carry a chromosomal abnormality involving the FGFR1 gene at chromosome 8p11. The novel chimeric proteins foster dimerization and ligand-independent activation of FGFR1 tyrosine kinase, subsequently promoting activation of downstream pathways involved in proliferation and malignant transformation of cells. Currently, 13 translocations and 1 insertion have been identified. Here, the current review mainly focuses on molecular genetic features, pathogenic mechanisms and therapy of EMS.
Chromosomes, Human, Pair 8 ; Humans ; Myeloproliferative Disorders ; classification ; genetics ; pathology ; Receptor, Fibroblast Growth Factor, Type 1 ; genetics

OBJECTIVETo study the clinical characteristics and diagnosis of the Johanson-Blizzard syndrome.

METHODThe clinical characteristics and diagnosing procedure of 1 case with Johanson-Blizzard syndrome were analyzed, and genetic analysis was made in diagnosing procedure, and 28 cases of Johanson-Blizzard syndrome with detailed clinical data were reviewed and analyzed.

RESULTA one year and nine months old girl, who was initially admitted to the hospital because of fatty diarrhea and increased frequency of defecation. Imperforate anus, and aplastic alae nasi was noticed after birth. On physical examination, short stature, mental retardation, tooth abnormalities and scalp defects were observed. Fat globule was found by routine stool test. Serum biochemistry showed an exocrine and endocrine pancreatic insufficiency, CT scan of the abdomen demonstrated fatty replacement of the pancreas, UBR1 gene analysis showed heterozygous for two missense changes. In all 29 cases, exocrine pancreatic insufficiency (72.4%) and hypoplasia of the alae nasi (93%) were the most common clinical manifestations, and sensorineural hearing loss (59%), scalp defects (69%) and hair thinning or upsweep of the hair (44.8%), hypothyroidism (44.8%), absence of permanent teeth (44.8%) and imperforate anus (21%) were also very common, but did not include consanguineous marriage of parents (10.3%).

CONCLUSIONJohanson-Blizzard syndrome is a rare autosomal recessive multisystem disorder, it is characterized by the association of congenital exocrine pancreatic insufficiency and hypoplasia or aplasia of the nasal wings, and can be diagnosed by clinical characteristics and UBR1 gene analysis.

Anus, Imperforate ; Deafness ; diagnosis ; genetics ; pathology ; Ectodermal Dysplasia ; diagnosis ; genetics ; pathology ; Female ; Growth Disorders ; Hearing Loss, Sensorineural ; Humans ; Hypothyroidism ; diagnosis ; genetics ; pathology ; Infant ; Intellectual Disability ; Nose ; abnormalities ; pathology ; Pancreatic Diseases ; diagnosis ; genetics ; pathology ; Ubiquitin-Protein Ligases ; genetics

This study evaluated the efficacy of a stepwise regimen of estradiol valerate for height control in girls with Marfan syndrome. Eight girls with Marfan syndrome who had completed estrogen treatment for height control were included. Estradiol valerate was started at a dose of 2 mg/day, and then was increased. The projected final height was estimated using the initial height percentile (on a disease-specific growth curve for Korean Marfan syndrome [gcPFHt]), and the initial bone age (baPFHt). After the estrogen treatment, the projected final height was compared to the actual final height (FHt). The median baseline chronological and bone age were 10.0 and 10.5 years, respectively. After a median of 36.5 months of treatment, the median FHt (172.6 cm) was shorter than the median gcPFHt (181.0 cm) and baPFHt (175.9 cm). In the six patients who started treatment before the age of 11 years, the median FHt (171.8 cm) was shorter than the median gcPFHt (181.5 cm) and baPFHt (177.4 cm) after treatment. The median differences between the FHt and gcPFHt and baPFHt were 9.2 and 8.3 cm, respectively. In two patients started treatment after the age of 11, the differences between FHt and gcPFHt, and baPFHt after treatment were -4 and 1.4 cm, and -1.2 and 0 cm for each case, respectively. A stepwise increasing regimen of estradiol valerate may be an effective treatment for height control in girls with Marfan syndrome, especially when started under 11 years old.
Body Height ; Child ; Contraceptive Agents/*therapeutic use ; Estradiol/*analogs & derivatives/therapeutic use ; Female ; Growth Disorders/pathology ; Humans ; Marfan Syndrome/diagnosis/*drug therapy ; Treatment Outcome

OBJECTIVETo analyze clinical manifestations and gene mutations in a child with severe short stature, explore its molecular mechanism and further clarify the diagnostic procedure for short stature.

METHODWe observed clinical characteristics of a patient with short stature and did diagnostic examinations, assessed the function of GH-IGF-1 axis, and surveyed its family members.Genomic DNA was extracted from peripheral blood, GHR, IGFALS, STAT5b and GH1 gene were amplified by PCR for sequencing, including exons and splicing areas.

RESULTThe patient presented symmetrical short stature (height -8.2 SDS) and facial features, and other congenital abnormalities.It displayed non-growth hormone deficiency. The baseline value of GH was 21 µg/L, and the peak was 57.9 µg/L. The value of IGF-1 was less than 25 µg/L, and the IGFBP-3 less than 50 µg/L. And IGF-1 generation test showed no response. There was no similar patients in the family members.Sequencing of GHR in the patient revealed a homozygous point mutation (c.Ivs6+1G>A), and her father and mother had the same heterozygous mutation. The same mutation was not identified for her sister.No other candidate gene was found.

CONCLUSIONAs the result of combined clinical characteristics and lab examinations, as well as gene detection, the case was diagnosed with Laron syndrome and GHR gene mutation is the molecular mechanism.We should explicit the etiological diagnosis for short stature, and avoid missed diagnosis and misdiagnosis.

Base Sequence ; Body Height ; Child ; DNA Mutational Analysis ; Exons ; Growth Disorders ; blood ; genetics ; pathology ; Human Growth Hormone ; blood ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; analysis ; Laron Syndrome ; blood ; genetics ; pathology ; Male ; Molecular Sequence Data ; Mutation ; Pedigree ; Receptors, Somatotropin ; genetics ; STAT5 Transcription Factor ; genetics

This study was aimed to investigate the clinico-pathological features, diagnosis and treatment of the 8p11 (eight p11) myeloproliferative syndrome (EMS). Morphological changes of cells were evaluated by bone marrow smear and biopsy. The cell immunophenotypes were analysed by flow cytometry. Karyotypes were determined by conventional cytogenetic method, and bcr/abl fusion gene was detected by reverse transcription-polymerase chain reaction (RT-PCR). The results indicated that EMS was a relatively rare disease characterized by the occurrence of a bcr/abl-negative myeloproliferative disorder and a T-cell lymphoblastic lymphoma (T-LBL). Bone marrow examination showed myeloid hyperplasia or myeloproliferative neoplasm, often accompanied by eosinophilia. Flow cytometric immunophenotyping showed increased myelomonoblasts; cytogenetic analysis showed a translocation at the 8p11 locus; RT-PCR demonstrated non bcr/abl fusion gene. At the molecular level, all cases carried a chromosomal abnormality involving the fibroblast growth factor receptor 1 (FGFR1) at chromosome 8p11. Up to now, 11 partner genes have been identified and associated with FGFR1 rearrangements. The most common partner is ZNF198 on chromosome 13q11-12. Majority of patients terminate in acute myeloid leukemia which is resistant to conventional chemotherapy. Currently, the only curative option appears to be allogeneic hematopoietic stem cell transplantation. In conclusion, EMS is myeloid and lymphoid neoplasm, associates with FGFR1 rearrangements. It is usually misdiagnosed as T-LBL, atypical chronic myeloid leukemia (aCML) or chronic myelogenous-monocytic leukemia (CMML). Timely cytogenetic and molecular biological examination is vital in order to avoid misdiagnosis and mistreatment.
Bone Marrow Cells ; pathology ; Chromosomes, Human, Pair 8 ; genetics ; Humans ; Male ; Middle Aged ; Myeloproliferative Disorders ; pathology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; pathology ; Receptor, Fibroblast Growth Factor, Type 1 ; genetics

Adult ; Azoospermia/genetics* ; Follicle Stimulating Hormone/metabolism* ; Gonadal Dysgenesis, Mixed/pathology* ; Growth Disorders/genetics* ; Humans ; In Situ Hybridization, Fluorescence ; Infertility, Male/genetics* ; Karyotype ; Luteinizing Hormone/metabolism* ; Male ; Mosaicism ; Testis/pathology* ; Testosterone/metabolism* ; Turner Syndrome