Claudette Hajaj Gonzalez

Are Noonan syndrome and Noonan-like/multiple giant cell lesion syndrome distinct entities?

We report on a family with typical clinical findings of Noonan syndrome associated with giant cell lesions in maxilla and mandible. We discuss the obvious clinical overlap between Noonan syndrome and Noonan-like/multiple giant cell lesion syndrome, and we give further clinical and molecular support that these two entities could be allelic conditions.

Hematological findings in Noonan syndrome

OBJECTIVE Noonan syndrome is a multiple congenital anomaly syndrome, and bleeding diathesis is considered part of the clinical findings. The purpose of this study was to determine the frequency of hemostatic abnormalities in a group of Noonan syndrome patients. METHOD We studied 30 patients with clinical diagnosis of Noonan syndrome regarding their hemostatic status consisting of bleeding time, prothrombin time, activated partial thromboplastin time and thrombin time tests, a platelet count, and a quantitative determination of factor XI. RESULTS An abnormal laboratory result was observed in 9 patients (30%). Although coagulation-factor deficiencies, especially factor XI deficiency, were the most common hematological findings, we also observed abnormalities of platelet count and function in our screening. CONCLUSIONS Hemostatic abnormalities are found with some frequency in Noonan syndrome patients (30% in our sample). Therefore, we emphasize the importance of a more extensive hematological investigation in these patients, especially prior to an invasive procedure, which is required with some frequency in this disorder.

Cardiac findings in 31 patients with Noonan's syndrome

OBJECTIVE To evaluate cardiac findings in 31 Noonan syndrome patients. METHODS Thirty-one (18 males and 13 females)patients from 26 families affected with Noonans syndrome were evaluated from the cardiac point of view with electrocardiography and Doppler echocardiography. RESULTS Twenty patients had some type of cardiac abnormality. The most frequent was pulmonary valve stenosis followed by hypertrophic myocardiopathy, commonly associated with valve defects. Upper deviation of the QRS axis was observed in 80% of these patients. CONCLUSION In view of the high frequency and diversity of cardiac abnormalities present in Noonan syndrome, cardiac evaluation with electrocardiography and echocardiography should be performed in all patients diagnostically suspected of having this disease.

In search of a genetic basis for the Rett syndrome

SummaryRett syndrome is a progressive encephalopathy restricted to the female sex. In the present paper a possible genetic cause for this syndrome is discussed, based on data from the literature as well as our own. Our results are in agreement with others regarding no increase in parental age, or in spontaneous abortions rate among the mothers of affected children and with a normal sex ratio among sibs. We have found no chromosome rearrangement detectable with the methods used and no correlation between fra(X)(p22) and the Rett syndrome. We have observed an alteration in the sequence of replication in one of the two types of late-replicating X-chromosome present in normal women, and suggest that this may signify that genes which are active in the late-replicating X-chromosome are inactivated (or vice-versa) in these patients. This fact could be related to the abnormal phenotype observed in Rett syndrome patients.

AEC Syndrome and CHAND Syndrome: Further Evidence of Clinical Overlapping in the Ectodermal Dysplasias

Abstract: Among the ectodermal dysplasias, there are several examples of overlapping phenotypes in disorders that are considered distinct. We report a 5‐year‐old boy born to nonconsanguineous parents and presenting with ectodermal dysplasia, ankyloblepharon filiforme adnatum, and bilateral choanal atresia consistent with the diagnosis of AEC syndrome. We compare the findings in our patient with the previous reported cases and discuss the overlapping phenotype of this disorder with CHAND syndrome.

Is Shwachman syndrome (McKusick 26040) a chromosome breakage syndrome

Tada et al. (1987) reported on increased spontaneous chromosome breakage in a female affected by Shwachman syndrome studied when 1, 3, and 10 months old. Fraccaro et al. (1988) observed a higher number of aberrations per cell in two sisters with this syndrome (10 and 8 months old) when compared to control cultures. The difference, however, was not statistically significant. The authors suggested that there might be an age-dependent influence. We had the chance to study two Caucasian Brazilian brothers, aged 46 and 25 months, affected by Shwachman syndrome, born to nonconsanguineous healthy parents. They have been followed at the Instituto da Crianga where their diagnosis was established. Since birth they have had chronic diarrhea with recurrent steatorrhea and several respiratory infections. The older had many episodes of otites and four episodes of single fracture of the left leg, soon after starting to walk. Both presented a protruding abdomen, abnormal pro-

Further delineation of Char syndrome.

comprising wide-set eyes, ptosis, very short philtrum, duckbill lips, low-set ears, patent ductus arteriosus (PDA) and the presence of only two phalanges in both fifth fingers.1 Four other families showing similar facial characteristics and PDA were described.2–5 This condition is now known as Char syndrome. In the present paper, we present a Brazilian family including three individuals affected by this disorder, in which the facial characteristics are striking.

Clinical and radiological aspects in Melnick-Needles syndrome

Melnick-Needles syndrome is an X-linked dominant bone dysplasia, lethal in males, characterized by a typical facies and characteristic radiological findings: including sclerosis of skull base and mastoids. S-shaped appearance of tibia; cortical irregularities with a ribbon appearance of the ribs. About 48 well-documented cases have been reported, most of them were sporadic. Parental transmission has been published in only 11 kindreds. We are presenting the first Brazilian family with mother-daughter transmission. The proposita presented the typical clinical and radiological features with characteristic facies, severe thoracic cage restriction and pulmonary hypertension. Her mother was more mildly affected.

Möbius Sequence in a Girl and Arthrogryposis in her Half-Brother: Distinct Phenotypes Caused By Prenatal Injuries

Möbius sequence is a congenital facial and abducens nerve palsy, frequently associated to abnormalities of extremities. Arthrogryposis multiplex congenital is defined as a congenital fixation of multiple joints seldom of neurogenic origin. Both sequences must have a genetic origin, but usually are sporadic cases related to environmental factors such as drugs exposition and maternal trauma. A 5-year-old girl and a 1-year-old boy were born with Möbius sequence and arthrogryposis multiplex congenital, respectively. During pregnancies, the mother had vaginal bleeding at 7 weeks and used crack (free-based cocaine) in the first trimester, respectively. The girl also has equinovarus talipes and autistic behavior. The boy has arthrogryposis with flexion contractures of the feet and knees. A vascular disruption, due to hemorrhage and cocaine exposure, causing a transient ischemic insult to embryos in a critical period of development may be responsible for distinct phenotypes in these cases.