Facebook
Twitter
LinkedIn
Email
 |
Checking for direct PDF access through Ovid | |
Excerpt
A white boy was born at 38 weeks of gestation by cesarean section because of fetal distress after an uncomplicated pregnancy (Figs. 1 and 2). At birth, he weighed 2,400 g (10th percentile), had a head circumference 36.8 cm (75th percentile), and had a meningomyelocele. The mother, age 25, was unrelated to her 29-year-old husband. No genetic diseases were reported in the families. At 4 months, the baby underwent laminectomy for Chiari malformation. He was admitted to our department at age 11 months. The physical examination revealed a broad forehead with a wide metopic suture and a large anterior fontanelle (6 × 6 cm), although the posterior was closed, micrognathia and cleft palate, low-set ears, pectus carinatum, contractures of the knees, pes cavus, plantar hyperkeratosis, and dysplastic toenails (Figs. 1 and 2). Dermatoglyphics were at right A, Lu, Lu, Lu, Lu and at left A, A, Lu, Lu, Lu.
A computed tomography scan of the brain showed minute bifrontal calcifications in the region of the gray–white matter junction and a type II Chiari malformation. Renal ultrasonography revealed a mild dilatation of the upper collecting system. Results of metabolic and serologic tests for toxoplasma, cytomegalovirus, and rubella were negative. The hemoglobin concentration was 7.1 g/dL, the hematocrit was 21.9%, the mean corpuscular volume was 90.3 fL, the white blood cell count was 7.480/mm3, the platelet count was 341,000/mm3, and the reticulocyte count was 0.7%. Hemoglobin electrophoresis was normal. Bone marrow examination showed normal cellularity with normal myeloid and megakaryocyte precursors. The erythroid compartment appeared markedly decreased (myeloid/erythroid ratio 20:1). The marrow cytogenetic analysis showed normal 46XY karyotype. Diepoxybutane test results were negative. The baby had increased serum values of folic acid (>20 ng/dL), vitamin B12 (932 pg/dL), and erythropoietin (>200 mU/mL). The clinical findings were suggestive for Diamond–Blackfan anemia (DBA). The child was transfused with packed red blood cells and treatment with oral prednisone was started. The hemoglobin level increased after treatment with 2 mg/kg per day prednisone, but the persistence of growth impairment after 3 months forced us to start transfusional therapy.
In approximately 30% of affected children, DBA is associated with congenital anomalies and malformations. The most common defects are craniofacial dysmorphisms, including cleft palate or hypertelorism, neck anomalies (pterygium colli up to congenital elevation of the scapula and Klippel–Feil syndrome), thumb malformations (triphalangeal, bifid, accessory, absent, hypoplastic, subluxed), and prenatal or postnatal growth failure. Various other anomalies are occasionally reported in association with DBA: urogenital malformations, congenital heart defects, hypogonadism, or ear malformations (3–5). Our patient had a rare combination of DBA with multiple anomalies related to a midline defect. They included meningomyelocele with type II Chiari malformation, cleft palate, and craniolacunia. The sequence of meningomyelocele includes different anomalies of the nervous system, including the Chiari malformation and craniolacunia (6).
In studying patterns of multiple anomalies, the midline has been considered a special kind of developmental field. The developmental field has been defined as units of the embryo in which the development of complex structures is determined and controlled in a spatially coordinated, temporally synchronous, and epimorphically hierarchical manner (7). The associations could derive from disruptive events acting on vulnerable developmental fields with the influence of other possible factors (genetic or environmental). Because of these relations and the implied causal heterogeneity, associations may have no distinct boundaries (8). Recently, genetic mapping studies have localized the gene responsible for DBA to a 1-Mb region on 19q13. Molecular studies found evidence for genetic heterogeneity in DBA without correlation between the 19q13 locus and the clinical expression of the disease (9).
