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The British Journal of Ophthalmology Nov 1982
Topics: Abnormalities, Multiple; Cataract; Dwarfism; Eye; Humans; Infant, Newborn; Male; Optic Nerve Diseases; Ribs; Syndrome
PubMed: 7126521
DOI: 10.1136/bjo.66.11.736 -
Ultrasound in Obstetrics & Gynecology :... Apr 2008We report the sonographic and autopsy findings in two sibling fetuses with autosomal recessive orofaciodigital syndrome (OFDS) Type IV (Mohr-Majewski) diagnosed at 11-13...
We report the sonographic and autopsy findings in two sibling fetuses with autosomal recessive orofaciodigital syndrome (OFDS) Type IV (Mohr-Majewski) diagnosed at 11-13 weeks' gestation. The first-trimester anomaly scan showed a markedly increased nuchal translucency (NT) thickness in both fetuses (4.7 mm and 5.1 mm). Both fetuses had multiple anomalies involving the brain, cranium, heart and skeletal system and their karyotypes were normal. The pregnancies were terminated and the autopsies showed findings consistent with Mohr-Majewski syndrome. These cases show the overlap between OFDS Type II (Mohr) and lethal short-rib-polydactyly syndrome Type II (Majewski) and confirm both the autosomal recessive inheritance of the condition and our ability to diagnose it early in pregnancy using detailed fetal ultrasonography.
Topics: Abortion, Therapeutic; Adult; Early Diagnosis; Female; Humans; Male; Nuchal Translucency Measurement; Orofaciodigital Syndromes; Pregnancy; Pregnancy Trimester, First
PubMed: 18383484
DOI: 10.1002/uog.5285 -
American Journal of Medical Genetics.... Nov 2009We report on a 3-year-old boy with prenatal onset of proportionate dwarfism, postnatal severe microcephaly, high forehead with receded hairline, sparse scalp hair,...
We report on a 3-year-old boy with prenatal onset of proportionate dwarfism, postnatal severe microcephaly, high forehead with receded hairline, sparse scalp hair, beaked nose, mild retrognathia and hypotonia diagnosed at birth as Seckel syndrome. At age 3 years, he became paralyzed due to a cerebrovascular malformation. Based on the clinical and radiological features showing evidence of skeletal dysplasia, the diagnosis was revised to Majewski osteodysplastic primordial dwarfism type II (MOPD II) syndrome. Western blot analysis of the patient's lymphoblastoid cell line lysate showed the absence of the protein pericentrin. Subsequent molecular analysis identified a novel homozygous single base insertion (c.1527_1528insA) in exon 10 of the PCNT gene, which leads to a frameshift (Treo510fs) and to premature protein truncation. PCNT mutations must be considered diagnostic of MOPD II syndrome. A possible role of pericentrin in the development of cerebral vessels is suggested.
Topics: Adult; Antigens; Base Sequence; Blotting, Western; Bone and Bones; Brain; Case-Control Studies; Child, Preschool; DNA Mutational Analysis; Diagnosis, Differential; Dwarfism; Female; Humans; Infant; Infant, Newborn; Magnetic Resonance Angiography; Male; Molecular Sequence Data; Mutation; Pregnancy; Radiography; Short Rib-Polydactyly Syndrome; Syndrome
PubMed: 19839044
DOI: 10.1002/ajmg.a.33035 -
The Indian Journal of Radiology &... May 2010Short rib polydactyly syndrome (SRPS) type 2 (Majewski syndrome) is a rare inherited, autosomal recessive, lethal skeletal dysplasia characterized by horizontally...
Short rib polydactyly syndrome (SRPS) type 2 (Majewski syndrome) is a rare inherited, autosomal recessive, lethal skeletal dysplasia characterized by horizontally located short ribs, pre- and postaxial polysyndactyly, and micromelia, with characteristic short ovoid tibiae. There may or may not be visceral involvement. We report a case of SRPS type 2 that was diagnosed by antenatal USG at 28 weeks of gestation; the diagnosis was subsequently confirmed by postnatal radiography, fetal autopsy, and histopathology.
PubMed: 20607029
DOI: 10.4103/0971-3026.63044 -
European Journal of Pediatrics Apr 1986The Dubowitz syndrome is a rare, autosomal, recessively inherited disorder of intrauterine and postnatal growth retardation leading to microcephaly, moderate mental...
The Dubowitz syndrome is a rare, autosomal, recessively inherited disorder of intrauterine and postnatal growth retardation leading to microcephaly, moderate mental retardation and such characteristic facial anomalies as telecanthus, epicanthic folds, blepharophimosis, ptosis, broadening of the bridge and tip of the nose, abnormal ears and retrogenia. Further findings include hyperactivity, eczema, cryptorchidism in the affected males, and brachy-clinodactyly of the fifth fingers. Thirty-three cases with this syndrome have been reported in the literature. Five additional patients are presented. All five are sporadic cases. The diagnostic symptoms and the differential diagnosis are discussed.
Topics: Abnormalities, Multiple; Child, Preschool; Face; Female; Fingers; Heart Defects, Congenital; Humans; Hyperkinesis; Infant; Intellectual Disability; Male; Microcephaly; Pregnancy; Syndrome
PubMed: 3709570
DOI: 10.1007/BF00496039 -
American Journal of Medical Genetics.... Sep 2004A description of the clinical features of Majewski osteodysplastic primordial dwarfism type II (MOPD II) is presented based on 58 affected individuals (27 from the... (Review)
Review
A description of the clinical features of Majewski osteodysplastic primordial dwarfism type II (MOPD II) is presented based on 58 affected individuals (27 from the literature and 31 previously unreported cases). The remarkable features of MOPD II are: severe intrauterine growth retardation (IUGR), severe postnatal growth retardation; relatively proportionate head size at birth which progresses to true and disproportionate microcephaly; progressive disproportion of the short stature secondary to shortening of the distal and middle segments of the limbs; a progressive bony dysplasia with metaphyseal changes in the limbs; epiphyseal delay; progressive loose-jointedness with occasional dislocation or subluxation of the knees, radial heads, and hips; unusual facial features including a prominent nose, eyes which appear prominent in infancy and early childhood, ears which are proportionate, mildly dysplastic and usually missing the lobule; a high squeaky voice; abnormally, small, and often dysplastic or missing dentition; a pleasant, outgoing, sociable personality; and autosomal recessive inheritance. Far-sightedness, scoliosis, unusual pigmentation, and truncal obesity often develop with time. Some individuals seem to have increased susceptibility to infections. A number of affected individuals have developed dilation of the CNS arteries variously described as aneurysms and Moya Moya disease. These vascular changes can be life threatening, even in early years because of rupture, CNS hemorrhage, and strokes. There is variability between affected individuals even within the same family.
Topics: Abnormalities, Multiple; Adolescent; Bone Diseases, Developmental; Cerebral Arterial Diseases; Child; Child Development; Child, Preschool; Craniofacial Abnormalities; Dwarfism; Female; Fetal Growth Retardation; Head; Humans; Infant; Infant, Newborn; Male; Personality; Puberty; Short Rib-Polydactyly Syndrome
PubMed: 15368497
DOI: 10.1002/ajmg.a.30203 -
Proceedings of the National Academy of... Apr 2016Lenz-Majewski syndrome (LMS) is a rare disease characterized by complex craniofacial, dental, cutaneous, and limb abnormalities combined with intellectual disability....
Lenz-Majewski syndrome (LMS) is a rare disease characterized by complex craniofacial, dental, cutaneous, and limb abnormalities combined with intellectual disability. Mutations in thePTDSS1gene coding one of the phosphatidylserine (PS) synthase enzymes, PSS1, were described as causative in LMS patients. Such mutations render PSS1 insensitive to feedback inhibition by PS levels. Here we show that expression of mutant PSS1 enzymes decreased phosphatidylinositol 4-phosphate (PI4P) levels both in the Golgi and the plasma membrane (PM) by activating the Sac1 phosphatase and altered PI4P cycling at the PM. Conversely, inhibitors of PI4KA, the enzyme that makes PI4P in the PM, blocked PS synthesis and reduced PS levels by 50% in normal cells. However, mutant PSS1 enzymes alleviated the PI4P dependence of PS synthesis. Oxysterol-binding protein-related protein 8, which was recently identified as a PI4P-PS exchanger between the ER and PM, showed PI4P-dependent membrane association that was significantly decreased by expression of PSS1 mutant enzymes. Our studies reveal that PS synthesis is tightly coupled to PI4P-dependent PS transport from the ER. Consequently, PSS1 mutations not only affect cellular PS levels and distribution but also lead to a more complex imbalance in lipid homeostasis by disturbing PI4P metabolism.
Topics: Abnormalities, Multiple; Bone Diseases, Developmental; Cell Membrane; Endoplasmic Reticulum; Golgi Apparatus; HEK293 Cells; Humans; Intellectual Disability; Minor Histocompatibility Antigens; Mutation; Nitrogenous Group Transferases; Phosphatidylinositol Phosphates; Phosphotransferases (Alcohol Group Acceptor)
PubMed: 27044099
DOI: 10.1073/pnas.1525719113 -
American Journal of Medical Genetics.... Nov 2013Sensenbrenner syndrome, also known as cranioectodermal dysplasia, is a rare multiple anomaly syndrome with distinctive craniofacial appearance, skeletal, ectodermal,... (Review)
Review
Sensenbrenner syndrome, also known as cranioectodermal dysplasia, is a rare multiple anomaly syndrome with distinctive craniofacial appearance, skeletal, ectodermal, connective tissue, renal, and liver anomalies. Dramatic advances with next-generation sequencing have expanded its phenotypic variability and molecular heterogeneity. We review 39 patients including two new patients, one with compound heterozygous novel mutations in WDR35 and a previously unreported multisutural craniosynostosis that may be a part of Sensenbrenner syndrome. In 14 of 25 (56.0%) patients pathogenic mutations have been identified in 4 different genes that regulate (intraflagellar) cilia transport. We compared Sensenbrenner syndrome to asphyxiating thoracic dystrophy-Jeune syndrome (ATD-JS) and other ciliopathies. Our analyses showed that the high anterior hairline, forehead bossing and dolichocephaly (accompanied by sagittal craniosynostosis in more than half of the patients) occur in almost all patients with Sensenbrenner syndrome. Metaphyseal dysplasia with narrow thorax, proximal limb shortness, and short fingers are typical of Sensenbrenner syndrome and ATD-JS. Respiratory complications have been reported in both syndromes, usually less severe with Sensenbrenner syndrome. Proposed diagnostic criteria for Sensenbrenner syndrome include the distinctive craniofacial appearance, ubiquitous brachydactyly and ectodermal anomalies, and sagittal craniosynostosis. Mild heart defects have been noted, but there have been no atrioventricular canal or heterotaxy defects that are common in Ellis-Van Creveld syndrome. We anticipate that the steady identification of molecularly defined patients may allow correlation of phenotype and genotype. Additional natural history data will improve genetic counseling and current guidelines.
Topics: Bone and Bones; Comparative Genomic Hybridization; Craniosynostoses; DNA Mutational Analysis; Ectodermal Dysplasia; Humans; Infant; Infant, Newborn; Karyotyping; Male; Phenotype
PubMed: 24123776
DOI: 10.1002/ajmg.a.36265 -
Archives of Gynecology and Obstetrics Jul 2005Short rib-polydactyly syndrome (SRPD) is an autosomal recessive, lethal skeletal dysplasia. It is characterized by short limb dwarfism, short ribs with thoracic...
INTRODUCTION
Short rib-polydactyly syndrome (SRPD) is an autosomal recessive, lethal skeletal dysplasia. It is characterized by short limb dwarfism, short ribs with thoracic hypoplasia, polydactyly, and multiple anomalies of major organs.
CASE REPORT
We report a case of SRPD subtype II (Majewski) that was detected in the 36th week of gestation, showing hydropic change, narrow thorax, shortened limbs, protuberant abdomen, micromelia, polydactyly and extremely low set ears, depressed nasal bridge, and cleft palate. The family was informed of the fatal outcome of the condition. Delivery was induced, and the baby died just after the birth.
DISCUSSION
Prenatal diagnosis is established with postmortem radiographic and pathologic examinations.
Topics: Adult; Diagnosis, Differential; Fatal Outcome; Female; Humans; Infant, Newborn; Male; Pregnancy; Short Rib-Polydactyly Syndrome; Ultrasonography, Prenatal
PubMed: 15605271
DOI: 10.1007/s00404-004-0696-9 -
Clinical Genetics May 1987Two patients with the oro-facial-digital syndrome II or Mohr syndrome presented laryngeal anomalies and hallucal and postaxial polysyndactyly of the feet. Those rare...
Two patients with the oro-facial-digital syndrome II or Mohr syndrome presented laryngeal anomalies and hallucal and postaxial polysyndactyly of the feet. Those rare malformations are typically observed in patients with the Majewski syndrome, a lethal, short rib-polydactyly skeletal dysplasia with orofacial findings almost identical to those of the Mohr syndrome. Phenotypic overlap between the Mohr and the Majewski syndromes has already been reported in the literature, and it has been suggested that the two syndromes may be mild and severe expressions of the same autosomal recessive disorder. Our two cases give further support to this hypothesis.
Topics: Abnormalities, Multiple; Child, Preschool; Female; Foot Deformities, Congenital; Hand Deformities, Congenital; Humans; Infant; Larynx; Orofaciodigital Syndromes; Osteochondrodysplasias; Phenotype; Short Rib-Polydactyly Syndrome
PubMed: 3608220
DOI: 10.1111/j.1399-0004.1987.tb02817.x