Biomedical subjects
Publications and source records attributed to B C Hamel.
Restrictive dermopathy is a rare autosomal recessive lethal skin dysplasia. It has been assumed that the characteristic morphologic abnormalities should allow a reliable prenatal diagnosis on fetal skin biopsies at about 20 weeks pregnancy. We report on a false-negative prenatal diagnosis.
During the period February to December 1990, 52 adult patients were referred to our clinic for evaluation of the presence of the Marfan syndrome. In 24 out of 52 patients the Marfan syndrome was diagnosed. Cardiac abnormalities were found in all patients: mitral insufficiency because of mitral valve prolapse (83%), aortic dilatation (67%), aortic insufficiency (38%), tricuspid valve insufficiency with or without tricuspid valve prolapse (17%) and atrial septal defect (4%). In 3 patients an aneurysm of the ascending aorta was found. Early recognition of the Marfan syndrome is relevant for prevention of the life threatening complication of aortic dissection. In patients with valve abnormalities endocarditis prophylaxis is advised. A Marfan outpatient clinic offers optimal diagnostic possibilities.
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We report on 3 siblings with an adult-onset, predominantly distal muscle weakness. In the female index patient this was associated with epilepsy and a progressive spastic ataxic gait, while the 2 other siblings had no appreciable clinical nervous system involvement. Additional investigations revealed muscular dystrophy and leukoencephalopathy in all 3 siblings. We conclude that this familial adult-onset muscular dystrophy associated with leukoencephalopathy represents a newly recognized autosomal recessive syndrome.
We report on nine patients with craniofrontonasal dysplasia (CFND). Seven classical cases had facial features suggestive of frontonasal dysplasia and coronal craniosynostosis. Extracranial abnormalities such as brittle nails with prominent longitudinal grooves or syndactyly of fingers and toes were observed in individual patients. In two families the father of classical cases showed a milder pattern of abnormalities, consistent with the diagnosis. We present a 2- to 13-year follow-up on our patients. Hypotonia and laxity of joints are common and may necessitate supportive measures. Mild developmental delay was noted in three out of six classical cases studied in detail. Unlike almost all other X-linked disorders, clinical expression in CFND is generally much more severe in females than in males. In contrast to previous reports of this condition, one of our severely affected cases is a male.
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In order to study the genetic aspects of the relation between neural tube defects and sex, we selected families with at least two closely related affected members. The sex ratios of both affected and normal transmitting persons were determined in these multiple case families. Our results indicate that there is a relation between the position of the lesion in the spine and sex. Furthermore, the affected persons in one family show significant concordance for sex as shown by the analysis of families with just two affected members. To our surprise, the group of normal transmitters appears to consist of significantly more females than males. This is in contrast to similar families with non-syndromic cleft lip +/- palate, where males predominate both among affected persons and normal transmitters. Finally, affected females most often inherited the predisposition to a neural tube defect from their mother. The possible role of inherited factors is discussed.
We describe four myotonic dystrophy (DM) patients who developed recurrent intestinal pseudo-obstruction. Some episodes were associated with gastroenteritis, while abdominal crowding may have occurred in one case during the third trimester of pregnancy. In most instances, however, no apparent cause could be identified. Intestinal pseudo-obstruction may occur at any stage of DM. In one of our cases intestinal pseudo-obstruction preceded significant muscle weakness by 15 years. Intestinal pseudo-obstruction is usually treated effectively with conservative measures. These include restriction of oral intake, intravenous fluids, and multiple enemas or colonoscopy. Improved intestinal function was noted in one case treated with the prokinetic agent cisapride. A partial sigmoid resection was performed in three cases with dolichomegacolon. No abnormalities were reported on histological examination. Since intestinal pseudo-obstruction is a rare complication of DM, it is of interest that two of our cases are sibs. Review of published reports showed several reports of familial occurrence of specific complications. These include cardiac conduction disturbances, focal myocarditis, mitral valve prolapse, pilomatrixomas, polyneuropathy, normal pressure hydrocephalus, and dilatation of the urinary tract. Myotonic dystrophy may show a tendency to familial clustering of organ specific involvement.
BACKGROUND: Restrictive dermopathy is an autosomal recessive phenotype characterized by universal tautness of skin resulting in fetal akinesia and death during the neonatal period. The clinical signs and symptoms of this uncommon disease are described in two brothers, and evidence is provided that fetal biopsy specimens obtained during the 20th week of gestational age are nondiagnostic. OBSERVATIONS: The first patient was a growth-retarded preterm boy suffering from generalized desquamation, marked joint contractures, and facial hypoplasia. Prominent light microscopic findings were hyperorthokeratosis intermingled with parakeratosis and absence of the elastic fibers in a thinned dermis. Electron microscopic examination of the epidermis revealed a lack of keratin filaments and an abnormal globular shape of the keratohyalin granules. The child died 4 days after birth. A following pregnancy resulted in birth of a preterm boy who died of the same disease within 2 hours. In the 20th week of gestational age, fetal biopsy specimens were obtained, but light and electron microscopy failed to reveal any abnormalities. CONCLUSIONS: Restrictive dermopathy is a genuine skin disease resulting in fetal akinesia that precludes a normal intrauterine development. The clinical features of this disorder are so distinctive that an on-the-spot diagnosis can be established. In view of the data obtained in this case, the feasibility of prenatal diagnosis should be regarded with great caution.
Myotonic dystrophy (DM) is well known for its highly variable clinical picture, including the age at which symptoms are first detected. In order to assess the proportion of asymptomatic gene carriers at different ages, we have used linked DNA markers to study individuals at 50% genetic risk of DM, in whom neurological examination, slit-lamp examination and electromyography (EMG) had failed to show diagnostic signs. A total of 139 asymptomatic offspring of DM patients were studied. Our analyses identified 11 out of these 139 as probable gene carriers. Our data show that penetrance of the DM gene increases with age. After correction for the possibility of genetic recombination between the DM gene and the DNA markers used, we calculated the residual chance of carrying the DM gene as 8.3% for clinically normal offspring aged between 20 and 39 yrs. We evaluated several factors that might influence this figure. Neither the sex of the propositus nor that of the affected parent modified the risk of carrying the DM gene. Presence of aspecific lens opacities also did not correlate with the risk of having inherited the DM gene. Since a significant proportion of DM gene carriers are not detected by neurological examination, including slit-lamp examination and EMG, these results confirm the need for DNA analysis in asymptomatic offspring of DM patients.
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Acrocallosal syndrome is an autosomal recessive disorder of brain malformation and complex polydactyly. We report on an additional patient with this disorder. It is suggested that increased birth weight and cerebellar hypoplasia occur in acrocallosal syndrome. The finding of an extra bone within the anterior fontanel in our patient suggests similarity to the Xt mouse mutant, which is homologous to Greig syndrome in man. This provides additional support for the hypothesis of allelism of the Greig and acrocallosal syndromes.
Hypophosphatasia with lung hypoplasia forms a lethal combination. A case with an a priori risk of 25% is reported in which the diagnosis was made by ultrasound.
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We report on two male and two female relatives with intestinal lymphangiectasia; severe lymphedema of limbs, genitalia, and face; facial anomalies; seizures; mild growth retardation; and moderate mental retardation. Main facial anomalies are a flat face, flat nasal bridge, hypertelorism, small mouth, tooth anomalies, and ear defects. Their parents are consanguineous. This disorder probably is an hitherto undescribed autosomal recessive syndrome.
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