David L. Rimoin

Leber's Congenital Amaurosis Associated with Familial Juvenile Nephronophthisis and Cone-Shaped Epiphyses of the Hands (the Saldino-Mainzer Syndrome)

Three affected children (a 13-year-old girl and her 7- and 8-year-old brothers) in a sibship of eight had findings consistent with the Saldino-Mainzer syndrome (skeletal dysplasia associated with Lebers congenital amaurosis, familial juvenile nephronophthisis, and cone-shaped epiphyses of the hands). Two also had pigmented midline nevi. Although tapetoretinal degeneration and familial juvenile nephronophthisis are associated in the inherited Senior-Loken syndrome, the rare association of these abnormalities with cone-shaped epiphyses of the hands suggested an autosomal recessive syndrome with variable expression remarkably similar to the Saldino-Mainzer syndrome, which may or may not be distinct from the Senior-Loken syndrome. The association of tapetoretinal degeneration with skeletal dysplasia may indicate asymptomatic renal or hepatic disease.

A search for heterogeneity in insulin dependent diabetes mellitus (IDDM): HLA and autoimmune studies in simplex, multiplex and multigenerational families☆

HLA antigens (A, B, C and DR loci), serum islet cell antibodies, thyrogastric antibodies, and insulin antibodies were studied in 77 families (25 simplex, 42 multiplex, and 10 multigenerational). In order to test for intrafamilial constancy and intergroup variation, we compared simplex with multiplex families, HLA identical and non identical siblings within families, as well as groups of families characterized by different DR alleles (DR3, DR4, and DR3/DR4) for various immunologic and clinical characteristics. These comparisons did not reveal all the distinct subgroups suggested by different cross-sectional population studies, but did provide evidence for a compound form having an aggregation of different high risk alleles. This study suggests that in many cases (and possibly especially in families with multiple affected individuals), there are several different genetic influences leading to IDDM.

Audiological findings of patients with achondroplasia

Skeletal dysplasias are a heterogeneous group of disorders which result in short stature and skeletal deformities. To date there are over 70 distinct recognizable conditions [15]. With the exception of two recent studies on patients with osteogenesis imperfecta [2,14] and Morquio syndrome [ 131, audiological evaluation on skeletal dysplasia patients have not been systematically obtained. In most cases data consist of casual observations, which were done on small numbers of patients where types of hearing loss and ranges or variability in hearing levels were not differentiated. This is particularly evident in discussion of audiologic status of patients with achondroplasia. Achondroplasia is an autosomal dominant skeletal dysplasia characterized by short stature, short limbs, and a variety of craniofacial abnormalities including a shortened cranial base, frontal bossing of the skull, and numerous dentofacial abnormalities. Gorlin et al. [ 6 ] and Cohen [3] reported a high incidence of otitis media in patient with achondroplasia. Hall 171, in a survey of 150 achondroplasts over the age of 18 years found that 75% reported having had ear infections and 11% reported that they ended up with a significant hearing loss. Glass et al. [5] in a study of 88 achondroplasts, found that 97% of the subjects reported having a history of ear infection and/or hearing loss. On pure-tone audiometric screening, 72% of the achondroplasts were found to have a hearing loss of 22 dB (ANSI1968) or greater. Based on these data the following questions arose. (1) Do achondroplasts have a higher incidence of hearing loss than other skeletal dysplasias? (2) What type of hearing loss is characteristic in achondroplasia? (3) What are