Differentiation of MISSLA and Fanconi anaemia by computer-aided image analysis and presentation of two novel MISSLA siblings.

Variants in DONSON were recently identified as the cause of microcephaly, short stature, and limb abnormalities syndrome (MISSLA). The clinical spectra of MISSLA and Fanconi anaemia (FA) strongly overlap. For that reason, some MISSLA patients have been clinically diagnosed with FA. Here, we present the clinical data of siblings with MISSLA featuring a novel DONSON variant and summarize the current literature on MISSLA. Additionally, we perform computer-aided image analysis using the DeepGestalt technology to test how distinct the facial features of MISSLA and FA patients are. We show that MISSLA has a specific facial gestalt. Notably, we find that also FA patients feature facial characteristics recognizable by computer-aided image analysis. We conclude that computer-assisted image analysis improves diagnostic precision in both MISSLA and FA.

Incidence of liver abnormalities in Fanconi anemia patients.

Patients with Fanconi anemia (FA) are prone to liver tumors, especially after androgen treatment, but other liver abnormalities have not been described for these patients. Here, we systematically reviewed liver manifestations in a cohort of 64 adult and pediatric patients with FA followed in a single center. "Significant biological liver abnormalities(SBLA)" in the absence of any androgen treatment were found in five patients, including two children, belonging to rare FA groups; these two patients presented with a very severe chronic cytolysis pattern which may be classified as a new FA phenotype. Liver radiological abnormalities, which include hepatic tumors (n 5 4), hepatomegaly(n 5 1), hyperechogenicity (n 5 2), and a previously undescribed biliary duct dilatation as demonstrated by magnetic resonance cholangiopancreatography(MRCP) (n 5 2), were found in eight patients who received androgen treatment or who had iron overload. Lastly, we found no correlation between cytolysis intensity and high levels of alpha-fetoprotein (AFP); this common finding in FA patients cannot therefore be explained by hepatocyte regeneration.

Fulminant limb and retroperitoneal necrotizing fasciitis in a 15-year-old girl with Fanconi anaemia.

Necrotizing fasciitis (NF) is an uncommon soft-tissue infection in children that carries a high mortality rate. We present a 15-year-old girl with chronic pancytopenia secondary to Fanconi anaemia who developed extensive NF of the lower limb, which unfortunately resulted in a fatal outcome. Immunodeficiency is a known risk factor for the development of this condition. The findings in this case demonstrate that patients with Fanconi anaemia may be susceptible to NF and that the clinical course may be more aggressive due to underlying immunosuppression. Prompt diagnosis of NF is vital in order to initiate appropriate treatment and to optimize patient outcome. Radiological investigation demonstrated extensive soft-tissue gas and destruction affecting the entire lower limb, abdominal wall and retroperitoneum, which led to timely definitive diagnosis and management.

Liver tumours in patients with Fanconi anaemia: a report of three cases.

Fanconi anaemia is an autosomal recessive disease, causing secondary aplastic anaemia and congenital abnormalities, associated with an increased risk of tumours. Liver cell adenoma and hepatocellular carcinoma have rarely been described. Clinical, radiological and histopathological features in three patients with Fanconi anaemia and liver tumours were analyzed. Only one patient had received androgens and none had chronic viral hepatitis. All had elevated serum ferritin with significant parenchymal iron overload. Alpha-fetoprotein levels were normal in all cases. Patient 1 had moderately differentiated hepatocellular carcinoma with venous invasion and satellite nodules. The patient underwent two consecutive resections. Patient 2 had hepatic nodules diagnosed at routine examination with radiological features of adenomas. The patient underwent resection, which showed liver cell adenoma with foci of carcinoma. Patient 3 had three nodules, with radiological and histological diagnosis of adenoma. In patients with Fanconi anaemia, androgen therapy and iron overload may contribute to the development of liver cell adenoma and hepatocellular carcinoma. Hepatocellular carcinoma may occur as a transformation of liver cell adenoma. With prolongation of survival, continued development of liver tumours can be expected. Routine detection should therefore be considered in these patients as curative resection can be performed.

Imaging of diffuse metastatic and dystrophic pulmonary calcification in children after haematopoietic stem cell transplantation.

The authors describe three cases of diffuse pulmonary calcification; two metastatic in children with acute transitory renal failure and the other dystrophic in a child with leukaemia. All three patients underwent haematopoietic stem cell transplantation (HSCT). Chest radiographs disclosed diffuse calcification within the lungs. The distribution of this calcification was bilateral but asymmetric. Diagnosis was made in two cases by high resolution computed tomography (HRCT) and in one case by HRCT and bone scan. Radiological characteristics, scintigraphic features, pathological mechanism and clinical outcome of such pulmonary calcification are discussed.

Prenatal diagnosis of Fanconi anemia (Group C) subsequent to abnormal sonographic findings.

Manifestations of Fanconi Anemia Complementation Group C (FA-C) include multiple major congenital malformations, hypoplastic radius, absent thumb, growth retardation, elfin-like facial features, microphthalmia, microcephaly, cafe-au-lait spots, early onset of hematologic disease and poor survival (Auerbach, 1997). We describe two cases in which second-trimester sonographic findings led to parental carrier testing for FA-C and subsequent prenatal diagnosis of affected fetuses.

Fanconi anemia associated with increased nuchal translucency detected by first-trimester ultrasound.

Increased nuchal translucency between 10 and 14 weeks of gestation has now been established as a marker for chromosomal defects in several large-scale studies. In addition, a growing number of structural defects and some rare genetic syndromes have been identified in association with this marker. We describe a case of a fetus with increased nuchal translucency at 12 weeks of gestation, in which second-trimester evaluation by ultrasound showed an enlarged cisterna magna, a ventricular septal defect and moderate signs of dysmorphia. Karyotyping by chorionic villus sampling revealed a high rate of chromosomal breaks. The diagnosis of Fanconi anemia with early onset was confirmed following the development of severe postnatal anemia 2 months after birth.

The clinical and radiological features of Fanconi's anaemia.

Fanconi's anaemia is a severe refractory anaemia, associated with congenital malformations in approximately two-thirds of cases. Although these malformations may involve every organ system, suggestive dysmorphic features include growth retardation, radial ray deformities and urinary malformations. These malformations are not specific for Fanconi's anaemia, but should be recognized during pregnancy, or later in childhood, and suggest the possibility of inherited haematopoiesis disorders.

A microdeletion syndrome due to a 3-Mb deletion on 19q13.2--Diamond-Blackfan anemia associated with macrocephaly, hypotonia, and psychomotor retardation.

We report on a boy with congenital pure red blood cell aplasia [Diamond Blackfan anemia (DBA)] and severe congenital hypotonia, macrocephaly, hypertelorism, a broad and tall forehead, medial epicanthus, and facial hypotonia with mouth-breathing and drooling, an affable and out-going personality, and a general psychomotor retardation. These features show similarity to the phenotype of the X-linked FG syndrome. DBA was diagnosed at the age of 4 months, and the boy underwent treatment with transfusion and with prednisolone. He had a normal 46, XY karyotype, but fluorescence in situ hybridization (FISH) analysis to metaphase chromosomes revealed a 3-Mb deletion on 19q13.2. This chromosomal region has previously been linked to the DBA phenotype and one 19q13 microdeletion has been identified in a patient with DBA. This deletion coincides with the deletion reported here. We suggest that the complex phenotype of our patient, including both DBA and the associated features, represent a microdeletion syndrome.

[Clinical and radiological diagnosis of Fanconi's anemia].

This paper reported 4 cases of Fanconi's anemia, which is a rare disease usually seen in children under 10 years of age. Its clinical features comprise familial pancytopenia, hypoplasia of bone marrow, and conspicuous megakaryophthisis, with multiple malformations predominantly occurring in the skeleton and kidney. Some cases may be associated with abnormalities of the chromosome.

Technetium colloid bone marrow imaging in Fanconi's anemia.

Four patients with Fanconi's anemia were evaluated with 99mTc-sulfur colloid bone marrow scans. The scans revealed similar paradoxical and irregular tracer distribution in all four patients. Normal to increased activity was demonstrated in the proximal metaphyses of the humeri with varying degrees of increased activity in more primitive marrow sites in the distal diaphyses of the humeri and tibia, the distal metaphyses of the humeri and femora, and the proximal metaphyses of the ulnae, radii, and tibia. Skip areas of normal distribution were seen in the proximal diaphyses of the humeri and femora. Although the scan reflects only the reticuloendothelial portion of bone marrow, it may be of some value in the differential diagnosis of pancytopenia.