ABSTRACT
Multiple congenital anomalies and craniofacial dysmorphism are characterizing the so-called Emanuel or supernumerary der(22)t(11;22) syndrome (OMIM609029). Mental and developmental retardation are major clinical features. The der(22) may arise from a parental balanced t(11;22)(q23;q11.2) or can be created de novo. Here we present a 2 years old boy with normal prenatal history, cyanotic at delivery and with ear anomalies, a preauricular tag, high-arched palate and micrognathia. There were neither microcephaly, nor heart or kidney defects. Psychological and motor testing at the age of 2 years confirmed significant mental and developmental delay. In addition, the child had seizures and an abnormal electroencephalogram. Cytogenetic and molecular analyses revealed a karyotype 47,XY,+der(22)t(11;22)(q23;q11.2). As parents refused further tests it could not be determined if the der(22) arose de novo or was parentally derived. Overall the present report should alert physician to offer cytogenetic and/or molecular diagnostics in comparable cases.
Subject(s)
Abnormalities, Multiple/diagnosis , Chromosome Disorders/diagnosis , Cleft Palate/diagnosis , Craniofacial Abnormalities/diagnosis , Developmental Disabilities/diagnosis , Heart Defects, Congenital/diagnosis , Intellectual Disability/diagnosis , Muscle Hypotonia/diagnosis , Seizures/diagnosis , Abnormalities, Multiple/genetics , Child, Preschool , Chromosome Disorders/genetics , Chromosomes, Human, Pair 22/genetics , Cleft Palate/genetics , Craniofacial Abnormalities/genetics , Developmental Disabilities/genetics , Heart Defects, Congenital/genetics , Humans , Intellectual Disability/genetics , Karyotyping , Male , Muscle Hypotonia/genetics , Seizures/geneticsABSTRACT
Wildervanck syndrome (WS) combines features of Klippel-Feil syndrome (KFS), sixth nerve palsy, and deafness. This is a case of a 23 year old woman, diagnosed with KFS (a triad of short neck, low posterior hairline and restricted neck movements) at the age of 20 days. The manifestations of the WS in this patient are severe: she has torticollis, and an extremely severe scoliosis. In addition, she is short (-3 SD; parental target height + 0.8SD) and has mixed sensorineural and conductive deafness. She also has ptosis, strabismus and a high myopia. Radiologically, there are multiple coalitions of cervical vertebrae. Intelligence is unaffected (IQ 95), but deafness, strabismus and high myopia forced her early out of school. Karyotype is 46, XX. In brief, this is a patient with severe WS and additional anomalies. Short and/or reduced parental target height is a part of WS.
Subject(s)
Abducens Nerve Diseases/diagnosis , Abnormalities, Multiple/diagnosis , Deafness/diagnosis , Duane Retraction Syndrome/diagnosis , Growth Disorders/diagnosis , Heart Defects, Congenital/diagnosis , Heart Septal Defects, Atrial/diagnosis , Klippel-Feil Syndrome/diagnosis , Lower Extremity Deformities, Congenital/diagnosis , Scoliosis/diagnosis , Torticollis/diagnosis , Upper Extremity Deformities, Congenital/diagnosis , Female , Humans , Severity of Illness Index , Young AdultABSTRACT
SGA (small for gestational age) is a child born with birth weight and/or length (BW/BL) under two standard deviations (2 SDS) for the gestational age and sex of the population. ~5% of all newborn children are SGA. A broad spectrum of factors are found to be causative: maternal, placental, foetal, metabolic, and genetic. In the newborn period the SGA children are at greater risk of life-threatening conditions: hypoglycaemia, hypercoagulability, necrotic enterocolitis, direct hyperbilirubinemia, hypotension, etc. Approximately 10 percent of SGA children do not achieve catch-up growth and remain short (≥-2 SDS) into adulthood. SGA people have an increased incidence of metabolic syndrome, coronary artery disease, stroke, low bone density and osteoporosis. SGA children aged more than 4 years with no evidence of spontaneous catch-up and with a height≥2.5 SD are considered for growth hormone (GH) treatment.
Subject(s)
Infant, Small for Gestational Age , Female , Humans , Incidence , Infant, Newborn , Male , Risk FactorsABSTRACT
Rare diseases (RDs) pose a significant set of problems for patients, since their disease and general social and health situation are often not recognized by the medical community and shunned by health insurance. The sheer number of RDs (5000-8000) and the number of patients (6-8% of the population) are challenging for every society. We wanted to get a better understanding of the rare diseases affecting the kidneys and urinary tract (RDAKUT) in the Republic of Macedonia and we investigated principally the PubMed Central articles of Macedonian medical professionals dealing with RDAKUT, but we also used information on RDAKUT from local sources. A significant number of RDs have been published, demonstrating the awareness and skill of Macedonian medical professionals despite pretty limited diagnostic facilities. We still feel that RDAKUT are underdiagnosed (e.g. Fabry's disease has not yet been reported), and that many patients with RDs have a long way to go before an accurate diagnosis. Increased awareness and ameliorated education are needed by the physicians; while health insurance must include RDAKUT covering their diagnosis and treatment costs. Neonatal screening for ~30 diseases (instead of just hypothyroidism) is also required. Patients' organizations exist and they are active in promoting their interests before of the health authorities.
Subject(s)
Rare Diseases , Urologic Diseases , Academic Medical Centers/statistics & numerical data , Adult , Child , Disease Management , Female , Humans , Male , Rare Diseases/diagnosis , Rare Diseases/epidemiology , Rare Diseases/therapy , Republic of North Macedonia/epidemiology , Urologic Diseases/diagnosis , Urologic Diseases/epidemiology , Urologic Diseases/therapyABSTRACT
Alkaptonuria (AKU) is a disorder of phenylalanine/tyrosine metabolism due to a defect in the enzyme homogentisate 1,2-dioxygenase (HGD). This recessive disease is caused by mutations in the HGD gene. We report a 14-year-old girl who was referred after presenting black urine. Careful examination revealed ochronosis of the conjunctiva. There was no affection of the cardiac valves. Elevated excretion of homogentisic acid in urine was found. Sequence analysis of the HGD gene from genomic DNA revealed that the patient is a compound heterozygote with a previously described mutation (c.473C>T, p.Pro158Leu), and a novel one (c.821C>T, p.Pro274Leu). Her mother is heterozygous for the novel mutation, while the brother is heterozygous for the previously described mutation. In summary, we describe an alkaptonuric patient with ocular ochronosis and a novel HGD mutation, c.821C>T, p.Pro274Leu.
Subject(s)
Alkaptonuria , Homogentisate 1,2-Dioxygenase/genetics , Ochronosis , Adolescent , Alkaptonuria/complications , Alkaptonuria/diagnosis , Alkaptonuria/genetics , Female , Humans , Mutation , Ochronosis/diagnosis , Ochronosis/etiologyABSTRACT
BACKGROUND: Mucopolysaccharidosis II (MPS II) is caused by a deficiency of iduronate-2-sulfatase (IDS; EC 3.1.6.13). METHODS AND RESULTS: We describe 11 boys from Bulgaria and Macedonia detected in the period from 1998 to 2008. The mean age at diagnosis was 4.77+/-1.29 years. All children were severely retarded: IQ ranged from 34-80, and they all had coarse faces and hepatomegaly. In addition, splenomegaly was found in 81.81% patients, dysostosis in 45.45%, kyphosis in 27.27%, deafness in 18.08%, growth below the third percentile in 45.45%, growth below the parental target height in all patients, stiff joints in 56.56% and hypertrophic myocardiopathy in 18.18% children. Two patients died at the age of 11 and 35 years. Plasma iduronate-2-sulfatase was low in all probands and normal in parents and relatives. Two new mutations were discovered: p.K236N (c.708G>C) in a child with a moderately severe phenotype, and p.Q80K (c.238C>A) which resulted in a severe phenotype and early death at the age of 11 years. Heterozygote carriers of the pathogenic allele were 29 female relatives. The calculated incidence rate for MPS II in Macedonia (censuses 1994 and 2002, children under 14 years: 483,923 and 426,280) and Bulgaria (censuses 1992 and 2006, children under 14 years: 1 126, 598 and 1,077,020) are 0.36 and 0.46 respectively, while the calculated prevalence rate are 3.6 and 4.6 per 1,000,000 boys (aged 0-14 years). Correlating phenotype and genotype remains a complex endeavour. CONCLUSIONS: We report calculated incidence and prevalence rates in two South Eastern European countries, and 2 novel genetic alterations correlated with their phenotypes.
Subject(s)
Glycoproteins/genetics , Mucopolysaccharidosis II , Adolescent , Adult , Bulgaria/epidemiology , Child , Child, Preschool , Female , Heterozygote , Humans , Incidence , Male , Mucopolysaccharidosis II/epidemiology , Mucopolysaccharidosis II/genetics , Mucopolysaccharidosis II/physiopathology , Mucopolysaccharidosis II/psychology , Mutation , Republic of North Macedonia/epidemiologyABSTRACT
INTRODUCTION AND OBJECTIVES: The objective of this study is to identify the nuclear expression of the p53 protein in prostate cancer and to determine its relationship with clinico-pathological variables. MATERIAL AND METHODS: The research included 83 patients, 43 of whom are patients with prostate cancer who underwent radical prostatectomy and a control group of 40 patients with benign hyperplasia of the prostate in whom a transurethral resection or a transvesical prostatectomy was undertaken. In all cases the nuclear expression of p53 protein was evaluated. A hystopatological evaluation of the tumour characteristics and the data of the local progression of the cancer were undertaken in the research group. RESULTS: The results show that the expression of the p53 protein does not have an important correlation with the preoperative PSA, but that it is in direct correlation with the malign potential of the cancer (Gleason score, Gleason sum, primary tumour) and with the features of the disease (metastatic lymph nodes, stage of the disease). CONCLUSION: p53 protein could be used as a valid biomarker in determining the malignant potential of the tumour and the prognosis of the disease. There is no practical use in predicting the extraprostatic extension.
