Light microscopic, histochemical and electron-microscopic studies were made on the brain of a case (No. 1) with Sanfilippo disease, type A. In this case pigment preparations of the isocortex have been demonstrated. Ultrastructural investigations of the skin biopsies (his two male siblings) were also studied (cases 2, 3). Our three siblings of MPS III A, have demonstrated ceroid lipofuscin storage in the brain (case No. 1) and skin biopsies (cases No. 2 and 3) in addition to histological features of MPS. The biochemical studies (enzymatic identification) were made in the cultures of fibroblasts. Also, urine quantitative studies for MPS and N-sulfonate to hexosamino ratio were performed.

Three cases of distal duplication 14q are presented. The first two cases are cousins in a kindred segregating a balanced translocation t(14;18)(q31;q23). The third case resulted from a maternal translocation t(14;18)(q24;p11). By review of these cases and those previously reported, a distal duplication 14q syndrome is further delineated. Common features include postnatal growth retardation, mental retardation, hypotonia, microcephaly, slanted palpebral fissures, ocular hypertelorism, sparse eyelashes and eyebrows, nasal dysmorphism, tented lip, micrognathia, posteriorly rotated ears, and minor skeletal anomalies.

No abstract

The syndrome of craniosynostosis and radial aplasia was first described by Baller in 19501 and Gerold in 1959.2 Greitzer et al3 subsequently described a fourth patient in 1974 with similar findings. The purpose of this report is to describe the findings in two additional cases that further delineate this syndrome. Report of Cases.\p=m-\Case1.\p=m-\Amale infant ( Figure) was the second child born to normal nonconsanguineous parents. The first pregnancy resulted in a normal infant. The patient was referred to the Mount Sinai School of Medicine, New York, at 5 weeks of age for evaluation of multiple congenital anomalies. His birth weight was 1.7 kg (< third percentile). Examination showed ridging of the lambdoid sutures and widely separated sagittal and metopic sutures with a large triangular anterior fontanel. The orbits were shallow thus causing a prominent proptosis. The ears were low set with a folded helix. He had a wide nasal bridge, anteverted nostrils, small downturned lips, and a high arched palate. Limb abnormalities consisted of bilateral absent thumbs, and absent radius and dysplastic ulna on the left, a hypoplas¬ tic radius and bowed ulna on the right, and contractures of both elbows. In addition, he had metatarsus adductus and clinodactyly of the second and fifth digits. Dermatoglyphic examination showed simian creases and a bilateral t' axial triradius.The anus was anteriorly placed.Findings from routine laboratory stud¬ ies including urinalysis, blood count, serum chemistries, plasma and urinary amino acids, and ECG were normal. Intravenous pyelogram showed one pelvic kidney and one kidney in normal position, both with normal dye excretion. Computerized axial tomography of the head demonstrated a normal ventricular system. Chromosomal analysis of cultured peripheral lympho¬ cytes from the patient and his parents revealed no abnormalities by Q, G and R banding techniques.The patient underwent a subtotal calvariectomy at 8 weeks of age. Special splints were devised to decrease elbow contracture and radial deviation at the wrist. At 5 months of age, the child was developmentally normal. However, his height and weight were below the third percentile.Case 2.-This 3-year-old female child was referred to the Center for Genetic Counsel¬ ing at the Boston Floating Hospital for Infants and Children because of coronal synostosis and limb deformities. Her moth¬ er was a 28-year-old gravida 1, para 1 and her father was 30 years old. The mother was diagnosed as having diabetes mellitus in 1967 and has been taking insulin. In the eighth month of pregnancy, preeclampsia was diagnosed in the mother. Delivery was by cesarean section be¬ cause of apparent cephalopelvic dispropor¬ tion. Birth weight was 2.2 kg. At birth, an absent radius was noted on the left, the humérus was hypoplastic, and there were only three metacarpale and two phalanges. On the right, there was considerable hypo¬ plasia of the radius with a curved ulna and an absent thumb. She also had coronal synostosis and a cardiac mumur that was subsequentl...

The X-linked fragile X [fra(X)] syndrome, associated with a fragile site at Xq27.3, is the most common Mendelian inherited form of mental deficiency. Approximately 1 in 1060 males and 1 in 677 females carry the fra(X) chromosome. However, diagnosis of carrier status can be difficult since about 20% of males and 44% of females are nonpenetrant for mental impairment and/or expression of fra(X). We analyzed DNA from 327 individuals in 23 families segregating fra(X) for linkage to three flanking polymorphic probes: 52A, F9, and ST14. This allowed probable nonpenetrant, transmitting males and carrier females to be identified. A combined linkage analysis was conducted using these families and published probe information on F9 in 27 other families, 52A in six families, and ST14 in five families. The two-point recombination fraction for 52A-F9 was 0.13 (90% confidence interval, 0.10-0.16), for F9-fra(X) was 0.21 (0.17-0.24), and for fra(X)-ST14 was 0.12 (0.07-0.17). Tight linkage between F9 and fra(X) was observed in some families; in others loose linkage was seen suggesting genetic linkage heterogeneity. Risk analysis of carrier status using flanking DNA probes showed that probable nonpenetrant transmitting males were included in families showing both tight and loose linkage. Thus, in contrast to our previous conclusions, it appears that the presence or absence of nonpenetrant, transmitting males in a family is not an indicator of heterogeneity. To determine if heterogeneity was present, we employed the admixture test. Evidence for linkage heterogeneity between F9 and fra(X) was found, significant at P less than 0.0005. Nonsignificant heterogeneity was seen for 52A-F9 linkage. No heterogeneity was found for fra(X)-ST14. The frequency of fra(X) expression was significantly lower in families with tight F9-fra(X) linkage than in families with loose linkage. Cognition appeared to relate to linkage type: affected males in tight linkage families had higher IQs than those in loose linkage families. These findings of genetic heterogeneity can account in part for the high prevalence and apparent high new mutation rate of fra(X). They will affect genetic counseling using RFLPs. An understanding of the basis for genetic heterogeneity in fra(X) will help to clarify the nature of the unusual pattern of inheritance seen in this syndrome.