Mandibuloacral dysplasia type A in childhood.

Mandibuloacral dysplasia type A (MADA) is characterized by growth retardation, postnatal onset of craniofacial anomalies with mandibular hypoplasia, progressive acral osteolysis, and skin changes including mottled pigmentation, skin atrophy, and lipodystrophy. Owing to its slowly progressive course, the syndrome has been recognized in adults, and pediatric case reports are scarce. We present the clinical case of two children in whom the diagnosis of MADA was made at an unusually early age. A 5-year-old boy presented with ocular proptosis, thin nose, and short and bulbous distal phalanges of fingers. A 4-year-old girl presented with round face and chubby cheeks, thin nose, bulbous fingertips, and type A lipodystrophy. In both, a skeletal survey showed wormian bones, thin clavicles, short distal phalanges of fingers and toes with acro-osteolysis. Both children were found to be homozygous for the recurrent missense mutation, c.1580G>A, (p.R527H) in exon 9 of the LMNA gene. Thus, the phenotype of MADA can be manifest in preschool age; diagnosis may be suggested by short and bulbous fingertips, facial features, and lipodystrophy, supported by the finding of acral osteolysis, and confirmed by mutation analysis.

Mowat-Wilson syndrome: facial phenotype changing with age: study of 19 Italian patients and review of the literature.

Mowat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene, and characterized by typical face, moderate-to-severe mental retardation, epilepsy, Hirschsprung disease, and multiple congenital anomalies, including genital anomalies (particularly hypospadias in males), congenital heart defects, agenesis of the corpus callosum, and eye defects. Since the first delineation by Mowat et al. [Mowat et al. (1998); J Med Genet 35:617-623], approximately 179 patients with ZEB2 mutations, deletions or cytogenetic abnormalities have been reported primarily from Europe, Australia and the United States. Genetic defects include chromosome 2q21-q23 microdeletions (or different chromosome rearrangements) in few patients, and ZEB2 mutations in most. We report on clinical and genetic data from 19 Italian patients, diagnosed within the last 5 years, including six previously published, and compare them with patients already reported. The main purpose of this review is to underline a highly consistent phenotype and to highlight the phenotypic evolution occurring with age, particularly of the facial characteristics. The prevalence of MWS is likely to be underestimated. Knowledge of the phenotypic spectrum of MWS and of its changing phenotype with age can improve the detection rate of this condition.

Massive hemobilia and papillomatosis of the gallbladder in metachromatic leukodystrophy: a life-threatening condition.

Polyposis of the gallbladder is rare during childhood. This condition can be associated with three other conditions: metachromatic leukodystrophy, Peutz-Jeghers' syndrome, and pancreaticobiliary maljunction. We report the case of a child with hemobilia in metachromatic leukodystrophy, which rendered cholecystectomy necessary. Macroscopically, the gallbladder measured 4.6 cm in length and showed an opaque serous surface and focal brown petechiae. Moreover, a yellow polypoid lesion of 2 cm in diameter and a diffuse thickening of the fundus wall were observed. Many reports describe the importance of the association of gallbladder papillomatosis with metachromatic leukodystrophy, but only three cases presented with massive intestinal bleeding, such as our young patient had. It is thus imperative that this life-threatening condition should be well known.

Holt-Oram syndrome associated with anomalies of the feet.

Holt-Oram syndrome (HOS) (OMIM 142900) is characterized by upper-extremity malformations involving the radial, thenar, or carpal bones and a personal and/or family history of congenital heart defects (CHDs). It is inherited in an autosomal dominant manner. The TBX5 gene located on chromosome 12 (12q24.1) is the only gene currently known to be associated with HOS and is associated with variable phenotypes. We report on the clinical and molecular characterization of a HOS family with three affected individuals and a novel mutation (Lys88ter). We discuss genotype-phenotype correlations, the presence of foot anomalies in one affected individual, and the role of atypical features in HOS differential diagnosis.

Congenital heart defects: 15 years of experience of the Emilia-Romagna Registry (Italy).

OBJECTIVES: Collection and assessment of data from the Emilia-Romagna Region on the occurrence of congenital heart defects in order to identify an homogeneous group of patients for further aetiologic and genetic studies. MATERIALS AND METHODS: The present study is based on 1549 stillborn and live born babies affected by congenital heart defect out of 330,017 consecutive births (4.7 per 1000). RESULTS: The frequency and type of congenital heart defects have been identified together with the sex ratio, associated extracardiac anomalies, chromosomal anomalies and the risk of precurrence in relatives. The impact of prenatal diagnosis on prevalence was low during the study period. CONCLUSIONS: The study has provided epidemiological data for public health surveillance of congenital heart defects in the Emilia-Romagna region. The creation of a system for the nationwide recording of congenital heart defects designed with regard to the sources of ascertainment, the diagnostic criteria, and the system of classification is emphasised.