ABSTRACT
SHORT syndrome (OMIM 269880) is a rare autosomal-dominant disorder characterized by short stature, hyperextensibility of joints, hernias, ocular depression, ophthalmic anomalies (Rieger anomaly, posterior embryotoxon, glaucoma), teething delay, partial lipodystrophy, insulin resistance and facial dysmorphic signs. Heterozygous mutations in PIK3R1 were recently identified in 14 families with SHORT syndrome. Eight of these families had a recurrent missense mutation (c.1945C>T; p.Arg649Trp). We report on two unrelated patients with typical clinical features of SHORT syndrome and additional problems such as pulmonary stenosis and ectopic kidney. Analysis of PIK3R1 revealed the mutation c.1945C>T; p.Arg649Trp de novo in both patients. These two patients not only provide additional evidence that PIK3R1 mutations cause SHORT syndrome, but also broaden the clinical spectrum of this syndrome and further confirm that the amino acid exchange c.1945C>T; p.Arg649Trp is a hotspot mutation in this gene.
Subject(s)
Genetic Predisposition to Disease/genetics , Growth Disorders/genetics , Growth Disorders/pathology , Hypercalcemia/genetics , Hypercalcemia/pathology , Metabolic Diseases/genetics , Metabolic Diseases/pathology , Nephrocalcinosis/genetics , Nephrocalcinosis/pathology , Phosphatidylinositol 3-Kinases/genetics , Class Ia Phosphatidylinositol 3-Kinase , DNA Primers/genetics , Female , Heterozygote , Humans , Male , Mutation, Missense/genetics , Polymerase Chain Reaction , Sequence Analysis, DNAABSTRACT
BACKGROUND: Since 2008, follow-up examinations at 2 years of age with the standardized Bayley II test have become obligatory in Germany for all very low birth weight infants. AIM: We already performed such examinations before 2006. Here, we compared our data and the completeness of our examinations before and after the introduction of the obligatory 2-year follow-up. PATIENTS: From 2004-2007, 372 infants <1500 g or <32 weeks were discharged alive from our center, 19 infants died during their initial hospital stay, 2 after discharge. RESULTS: 271 patients participated in the follow-up examination at age 2 years, with the proportion of participating infants increasing from 64% to 84% after the introduction of obligatory tests. 75% of infants showed a normal development, while 4% had a severe impairment (defined as being blind (1), deaf (1) or having cerebral palsy (6), the CP rate thus being 2%). 49% of infants completed the Bayley test; the mean MDI was 100.3 (SD 10.6). There were no significant qualtitative differences in test results with the introduction of the obligatory test. CONCLUSIONS: The completeness of our follow-up increased over the years. In comparison with international data we found a low rate of severely impaired, deaf or blind VLBW infants.
Subject(s)
Developmental Disabilities/diagnosis , Infant, Premature, Diseases/diagnosis , Infant, Very Low Birth Weight , Neurologic Examination , Blindness/diagnosis , Blindness/epidemiology , Cerebral Palsy/diagnosis , Cerebral Palsy/epidemiology , Child, Preschool , Cross-Sectional Studies , Deafness/diagnosis , Deafness/epidemiology , Developmental Disabilities/epidemiology , Female , Follow-Up Studies , Germany , Humans , Infant , Infant, Newborn , Infant, Premature, Diseases/epidemiology , MaleABSTRACT
Wolf-Hirschhorn syndrome (WHS) is a multiple malformation syndrome caused by partial monosomy of 4p16.3. Pitt-Rogers-Danks syndrome, first thought to be a distinct entity, is a similar condition associated with a microdeletion overlapping the WHS critical region. In this paper we evaluate three WHS patients showing a microdeletion of 4p and remarkable development with respect to the clinical spectrum of WHS.
Subject(s)
Abnormalities, Multiple/genetics , Chromosome Deletion , Chromosomes, Human, Pair 4/genetics , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/physiopathology , Adolescent , Adult , Amniocentesis , Child , Child, Preschool , Diseases in Twins/diagnosis , Diseases in Twins/genetics , Female , Humans , In Situ Hybridization, Fluorescence , Infant , Infant, Newborn , Karyotyping , Male , Maternal Age , Polymorphism, Genetic , Pregnancy, High-Risk , Syndrome , Ultrasonography, PrenatalABSTRACT
In most cases the etiology of the focal ischemic stroke in newborns is still obscure. We considered patients with congenital hemiparesis due to a lesion in the territory of the middle cerebral artery (shown by CT or MRI) as a model of this infarction. A detailed history including maternal and familiar data was obtained from 9 affected patients. Duplex-sonography was performed and biochemical parameters were analysed in all patients and their mothers. There were no convincing hints for a prenatal (for instance infectious, traumatic or toxic) origin. Also the reconstruction of the perinatal period could not explain the infarction. Duplex-sonography revealed no anatomic variants of the intra- or extracerebral arteries. Haemostasiological results were within normal limits--except the antiphospholipid antibodies, which were detected in 7 of the 9 families (patient or mother). The significance of these results is still unknown. We propose, antiphospholipid antibodies and further haemostasiological parameters should be investigated as near as possible to the neonatal period.
Subject(s)
Cerebral Infarction/etiology , Adolescent , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/diagnostic imaging , Cerebral Infarction/diagnostic imaging , Child , Child, Preschool , Female , Follow-Up Studies , Hemostasis/physiology , Humans , Infant , Infant, Newborn , Male , Pregnancy , Prenatal Exposure Delayed Effects , Risk Factors , Ultrasonography, Doppler, TranscranialABSTRACT
Pathogenic events affecting the developing brain cause malformations or lesions, the pattern of which depend on the stage of brain development. While in the past diagnosis of these patterns was made by post mortem examinations, today advances of brain imaging allow this already during life time. The patterns of hypoxic-ischemic brain injuries on magnetic resonance imaging (MRI) are well known for the older child (after progress of myelination). This paper addresses the question how early and how specific these patterns can be recognized by two imaging methods, e.g. cranial ultrasound and magnetic resonance imaging. It concludes, that neonatal MRI but also neonatal ultrasound can reliably detect major lesions but may fail in the detection of less extensive patterns. Most authors therefore conclude, that a routine use of MRI for the detection of hypoxic-ischemic lesions during the neonatal period is not recommended and should rather be reserved for later controls.
