Mazabraud syndrome in two patients: clinical overlap with McCune-Albright syndrome.

Mazabraud syndrome is a rare sporadic disorder, mainly characterized by bone fibrous dysplasia and intramuscular myxomas. We report here two new cases of Mazabraud syndrome. One of our patients (Patient 1) also had café-au-lait spots and multinodular goiter suggestive of McCune-Albright syndrome. We review the 37 previously reported cases with Mazabraud syndrome and discuss the 6/37 patients with criteria of Mazabraud and McCune-Albright syndromes. Based on the clinical overlap between the two syndromes, we tested the GNAS1 gene in blood leukocytes and skin fibroblasts of Patient 1, but found no evidence of an activating mutation in the GNAS1 gene.

Prenatal diagnosis of sporadic Apert syndrome: a sequential diagnostic approach combining three-dimensional computed tomography and molecular biology.

Apert syndrome is characterized by coronal craniosynostosis, midfacial hypoplasia, symmetrical syndactyly of the hands and feet described as 'mitten-like' with varying degrees of mental retardation. It results from a mutation of the fibroblast growth factor-2 (FGFR2) gene. In the absence of a family history, prenatal diagnosis may be difficult based on sonography alone. We report a case in which the prenatal diagnosis of Apert syndrome was suspected by ultrasonography, established by three-dimensional computed tomography scan (3DTS) and confirmed by the detection of a mutation on amniotic cells. This underscores the usefulness of a sequential diagnostic approach combining 3DTS and molecular biology in cases in which sonography alone is not con- clusive.

Fibrodysplasia ossificans progressiva, a heritable disorder of severe heterotopic ossification, maps to human chromosome 4q27-31.

Fibrodysplasia ossificans progressiva (FOP) is a severely disabling, autosomal-dominant disorder of connective tissue and is characterized by postnatal progressive heterotopic ossification of muscle, tendon, ligament, and fascia and by congenital malformation of the great toes. To identify the chromosomal location of the FOP gene, we conducted a genomewide linkage analysis, using four affected families with a total of 14 informative meioses. Male-to-male transmission of the FOP phenotype excluded X-linked inheritance. Highly polymorphic microsatellite markers covering all human autosomes were amplified by use of PCR. The FOP phenotype is linked to markers located in the 4q27-31 region (LOD score 3.10 at recombination fraction 0). Crossover events localize the putative FOP gene within a 36-cM interval bordered proximally by D4S1625 and distally by D4S2417. This interval contains at least one gene involved in the bone morphogenetic protein-signaling pathway.

SHORT syndrome: a case with high hyperopia and astigmatism.

We describe a case of the SHORT syndrome and compare it with previously published cases. This six-year-old girl shows nearly all the typical manifestations reported in patients with the SHORT syndrome, including lipoatrophy, minor facial anomalies, Rieger anomaly, and short stature. However, she also suffers from high hyperopia and astigmatism associated with poor visual acuity.

CHARGE syndrome: report of 47 cases and review.

The acronym CHARGE refers to a syndrome of unknown cause. Here we report on 47 CHARGE patients evaluated for the frequency of major anomalies, namely coloboma (79%), heart malformation (85%), choanal atresia (57%), growth and/or mental retardation (100%), genital anomalies (34%), ear anomalies (91%), and/or deafness (62%). In addition, we comment on anomalies observed very frequently in neonates and infants with the CHARGE syndrome, including, minor facial anomalies, neonatal brain stem dysfunction with cranial nerve palsy, and, mostly, internal ear anomalies such as semicircular canal hypoplasia that were found in each patient that could be tested. We propose several criteria for poor survival including male gender, central nervous system and/or oesophageal malformations, and bilateral choanal atresia. No predictive factor regarding developmental prognosis could be identified in our series. A significantly higher mean paternal age at conception together with concordance in monozygotic twins and the existence of rare familial cases support the role of genetic factors such as de novo mutation of a dominant gene or subtle sub-microscopic chromosome rearrangement. Finally, the combination of malformations in CHARGE syndrome strongly supports the view that this multiple congenital anomalies/mental retardation syndrome is a polytopic developmental field defect involving the neural tube and the neural crests cells.

Idiopathic thrombocytopenic purpura in two mothers of children with DiGeorge sequence: a new component manifestation of deletion 22q11?

The phenotypic spectrum caused by the microdeletion of chromosome 22q11 region is known to be variable. Nearly all patients with DiGeorge sequence (DGS) and approximately 60% of patients with velocardiofacial syndrome exhibit the deletion. Recent papers have reported various congenital defects in patients with 22q11 deletions. Conversely, some patients have minimal clinical expression. Ten to 25% of parents of patients with DGS exhibit the deletion and are nearly asymptomatic. Two female patients carrying a 22q11 microdeletion and presenting with idiopathic thrombocytopenic purpura are reported. Both had children with typical manifestations of DGS.

Prenatal diagnosis of cleft lip at 11 menstrual weeks using embryoscopy in the van der Woude syndrome.

On the basis of prenatal identification of a cleft lip by embryoscopy, a case of van der Woude syndrome was diagnosed at 11 menstrual weeks, allowing for early termination of pregnancy. The potential of embryoscopy to detect minor malformations in early pregnancy is discussed from both the technical and the ethical point of view.

Meckel-Gruber syndrome: prenatal diagnosis at 10 menstrual weeks using embryoscopy.

A case of Meckel-Gruber syndrome was diagnosed by embryoscopy at 10 menstrual weeks, allowing for early termination of pregnancy. Post-mortem examination confirmed the presence of polydactyly and bilateral cystic lesions of the mesonephros and metanephros. Both the forming nephrons and the collecting ducts were involved in the formation of renal cysts.

Hypothyroidism in children with filter paper TSH of 30 to 50 microU/ml at initial screening. Implication of the TSH cut-off point for recalling of infants at risk.

In a systematic screening of newborns in France during the period from 1979 to 1983, 959 infants with hypothyroidism were detected. In 16 cases of confirmed hypothyroidism the initial filter paper TSH (FP-TSH) was between 30 and 50 microU/ml. These cases emphasize the necessity of keeping a "security zone" for FP-TSH value between 30 and 50 microU/ml and of recalling these patients for a second test filter paper TSH.

[Congenital or neonatal hypothyroidism with filter-paper levels of TSH less than 50 microU/ml. Conclusions on the detection strategy in France]. / Hypothyroïdie congénitale ou néonatale avec "TSH papier de dépistage" inférieur à 50 microU/ml. Conclusion sur la stratégie du dépistage en France.

Between 1979 and 1983, 959 hypothyroid infants were discovered by the neonatal screening program in France. Sixteen had filter-paper TSH levels between 30 and 50 microU/ml: one was athyroid, ectopic thyroid in 5,10 had thyroids in place. These latter 16 cases argue for a second TSH control-value for filter paper TSH values between 30 and 50 microU/ml.