Distichiasis, congenital heart defects and mixed peripheral vascular anomalies.

We report on a previously apparently unreported syndrome of distichiasis with congenital heart defects and with mixed peripheral vascular anomalies in a mother and her four children. The mother had a ventricular septal defect; both daughters had surgery for patent ductus arteriosus. Sinus bradycardia alone (elder son), with stress induced asystole (younger son), and with wandering atrial pacemaker (both daughters) are documented electrocardiographically. Three of the five have edema, two have visible varicosities, three have symptoms consistent with chronic venous disease of the legs, and the older daughter has complaints consistent with arterial disease in the legs. Doppler flow studies demonstrated post-phlebitic syndrome in all but the younger daughter, and vasospastic disease in the mother, older daughter, and second son.

The SC phocomelia syndrome: report of two cases with cytogenetic abnormality.

We report two sibs with the SC phocomelia syndrome with typical facial appearance and bilateral absence or extreme hypoplasia of the fibula, radius, and thumb. One sib had bilateral humero-ulnar and femoro-tibial synostosis (absence of the elbow and knee joints). Application of the nosologic criteria of Herrmann and Opitz showed that there was no significant intrafamilial variation in phenotype. Chromosome analyses in both patients showed heterochromatic puffing and centromere separation involving many chromosomes, an observation that has previously been reported in patients with SC phocomelia and Roberts syndromes. More important, this finding will have significance in prenatal detection of a certain proportion of cases with these syndromes without resorting to the use of radiographic examinations.

A familial dilated cardiomyopathy associated with cataracts and hip-spine disease.

A dilated cardiomyopathy was observed in two generations of a kindred, associated with articular disease and premature cataracts, a unique triad not previously described to our knowledge. The cardiomyopathy was characterized histologically by basophilic PAS-positive granulofilamentous deposits in the myocardium. The articular disease included hip joint degeneration, irregular intervertebral disks, and platyspondyly. The lenticular abnormalities may occur in young adults prior to other manifestations of the triad. Consanguinity was noted in the parents, and inheritance was most compatible with an autosomal recessive trait, with variable penetrance and expressivity.

Fetal alcohol syndrome at the turn of the 20th century. An unexpected explanation of the Kallikak family.

At the turn of the 20th century, studies of a family known in the literature as the Kallikaks were used to document the hereditary nature of mental retardation, poverty, and antisocial behavior. This family was said to authenticate eugenic theory, which states that heritable characteristics carried by individuals on "independent unit characters are unalterable determinants of behavior and performance. A review of the original Kallikak data, however, suggests that in utero exposure to alcohol rather than heredity contributed significantly to the transgenerational learning failure seen throughout the Kallikak pedigree. However, eugenic theory was so thoroughly accepted that the promotion and acceptance of "hereditary feeblemindedness" as the principal cause of the developmental problems in the affected offspring smothered the research efforts on in utero effects of alcohol until long after the eugenic concepts were abandoned later in the century.

I-cell disease (mucolipidosis II). Differential expression in satellite cells and mature muscle fibers.

A well documented case of I-cell disease is presented. Light- and electron-microscopic studies of muscle revealed marked accumulation of characteristic I-cell inclusions in satellite cells and only scattered autophagic vacuoles in muscle fibers. Correlation with previous tissue culture studies indicated an amelioration of structural abnormalities with differentiation from satellite cell to mature muscle fiber. Histochemically, the muscle demonstrated paucity of type I fibers without evidence of denervation thus suggesting a developmental disturbance in motor unit organization. Selective type I fiber dysfunction and reduced satellite cell regenerative capacity may be related factors in the neuromuscular disability of patients with I-cell disease.

Abnormal distal phalanges and nails, deafness, mental retardation, and seizure disorder: a new familial syndrome.

A 10-year-old boy and his 9-year-old sister, with abnormalities of distal phalanges of hands and feet, onychodystrophy, deafness, mental retardation, seizure disorder, and abnormal dermatoglyphics, are described. Six similarly affected patients have been reported. These eight patients represent a new syndrome, which is inherited as an autosomal recessive trait.

A possible major contribution to mental retardation in the general population by the gene for microcephaly.

In a study of 13 families with genetic microcephaly, it was found that 11 of 24 parents (two fathers not ascertained) and 11 of 33 non-microcephalic siblings were of subnormal intelligence. In a rare autosomal recessive condition, all parents and two-thirds of unaffected siblings are presumed carriers of the gene. It so, nearly 50% of all presumed heterozygotes in the present study were mentally retarded. The proportion agrees well with the other major study of microcephaly in North America, but differs from the Dutch study. On the basis of pooled data from the three studies and the estimated incidence of 1:40000 for genetic microcephaly, it is postulated that (1) about 0.34% of the general population is mentally retarded because it is carrying the gene for microcephaly and (2) about one of nine mentally retarded individuals is heterozygous for the gene for microcephaly.

Temporary increase in chromosome breakage in an infant prenatally exposed to lead.

An infant exposed to high levels of lead in utero was found to have increased numbers of cells with chromosome breaks in blood samples obtained at 6 weeks and 3 months of life. Later samples did not show significant abnormality. Physical and neurological examinations of the patient up to 18 months of age gave results within normal limits.

Distal 18q deletion without clinical findings of 18q- syndrome.

A de nova translocation of long arm of chromosome 3 to the distal third of long arm of 18 was detected in a 10 years old boy, whose phenotype has been somewhat affected. Although the translocation has resulted in loss of distal segment of 18q, clinically he bears little resemblance to 18q- syndrome.

Direct insertion of euchromatic material from chromosome Y in the X-chromosome in hypogonadotropic hypogonadisms with Crohn's disease.

The relationship between chromosomal abnormalities and Crohn's disease has not been established. Crohn's disease is associated with inflammation of the bowel, severe abdominal pain and chronic diarrhea. Its etiology is not known at present. A recessive gene with incomplete penetrance is thought to be a factor which does not follow simple mendelian inheritance. We report a case, where the euchromatin material of Y chromosome (p11.1 p11.2) has been directly inserted into the long arm of the X chromosome (q21.2), and is assumed to be the most likely cause of hypogonadotropic hypogonadism in this patients. It could also be that the function of the testis-determining factor (SRY) has been disrupted due to the insertion, causing loss of testicular development.

Symphalangism with metacarpophalangeal fusions and elbow abnormalities.

Three generations of a family manifest similar skeletal abnormalities: proximal symphalangism with several unusual features, metacarpophalangeal synostoses, massive tarsal and carpal fusions and abnormalities of the elbows (radial head dislocation, radiohumeral synostosis). Two members of this family were previously reported by Pearlman et al. as examples of the Nievergelt syndrome, but the affected individuals lack the mesomelic dysplasia that is an integral part of that entity. Moreover, the Nievergelt syndrome does not include symphalangism. The term "Nievergelt-Pearlman syndrome" should be dropped.

Crossed asymmetry in Russell-Silver syndrome.

Since the initial report by Silver et al (1953), more than 50 examples of the Russell-Silver syndrome have been reported. Unilateral congenital asymmetry of the extremities has been considered one of the major features of this disorder (Silver, 1964). We recently observed a child with otherwise typical features of the Russell-Silver syndrome who had enlargement of the right hand and of the left lower extremity. We know of no other recorded example of crossed asymmetry in this clinical entity.

Trisomy 9 syndrome.

An infant is described with multiple congenital anomalies associated with mosaic trisomy 9. Review of the three previously reported cases of trisomy 9 shows that these patients have several common features which make trisomy 9 a clinically distinct syndrome. The frequently encountered findings are: upward-slanted eyes, small palpebral fissures, enophthalmos or microphthalmos, broad base and prominent tip of the nose, microcephaly, micrognathia, low-set malformed ears, high-arched palate, congenital heart disease, skeletal and genito-urinary anomalies, abnormal palmar creases, failure to thrive, hypotonia and retardation.