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We report on a male child with "apple peel" atresia, associated with microcephaly, with subsequent hydrocephalus, short stature, moderate global developmental delay and ocular abnormalities. A similar phenotype was previously reported by Stromme et al. in 1993 in female siblings, and this description of another affected individual provides further evidence for this being a distinct syndromic entity.

Hereditary gingival fibromatosis is a rare condition occurring as an isolated anomaly or as part of a genetic syndrome. The isolated or syndromic disorders are usually inherited in an autosomal dominant manner, but an autosomal recessive form has been suggested. We report on male and female siblings who have gingival fibromatosis in association with specific facial dysmorphism. Their phenotype is depicted and described to document this hitherto unreported autosomal recessive gingival fibromatosis syndrome.

A kindred is described in which five male members over three generations manifested a high-frequency deafness. Their isolated sensorineural hearing loss was non-progressive and only in the 1500-8000 Hz range. The pattern of inheritance and nature of the auditory deficit would suggest it is a previously undescribed X-linked form of deafness.

Four members in three generations of a family had Rapp-Hodgkin hypohidrotic ectodermal dysplasia syndrome with variable involvement of teeth, hair, nails and palate, characteristic facies and mild heat tolerance problems. In addition, the proband had a high sweat sodium, hypogenitalism, hypothelia and marked cicatricial scalp atrophy and scarring. Inheritance of the condition was consistent with an autosomal dominant mode and the manifestations are described to delineate further this rare phenotype.

The osteopetroses are a heterogeneous group of disorders characterised by generalised bony sclerosis. The autosomal dominant form usually has a "benign" prognosis, in contrast to the "malignant" course of the autosomal recessive variety. In this paper we describe a kindred in which the phenotypic spectrum varied from an asymptomatic condition in adults to a severely affected infant, presenting with anaemia, hepatosplenomegaly, hydrocephalus and blindness. The findings in this family are reported and discussed to elucidate further the possible genetic heterogeneity in autosomal dominant osteopetrosis.

Plasma lipid and serum apoprotein concentrations were determined in twenty-nine individuals with Gaucher type I disease. Plasma total cholesterol, low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol were all significantly reduced in the patients with Gaucher disease compared to a group of matched control subjects. Total, LDL and HDL cholesterol were lower in males than in females with Gaucher disease. These sex differences appeared to be inversely correlated with the severity of disease manifestations which were greater in the males. Serum levels of apoprotein-B and apoprotein-AI, the major structural apoproteins of LDL and HDL, respectively, were decreased in the subjects with Gaucher disease. Thus, the reductions in LDL and HDL cholesterol were associated with reduced numbers of lipoprotein particles in plasma. In contrast, apoprotein-E, a protein which is secreted by several tissues, including activated macrophages and which may mediate hepatic catabolism of lipoproteins, was elevated in the patients. Since macrophages may also catabolize lipoproteins, Gaucher disease may serve as a model for the effect of activated macrophages upon human lipoprotein metabolism.

A mother and her four children had gross generalized joint laxity, with multiple dislocations and subluxations, moderate skin hyperextensibility and mild connective tissue fragility. Their condition could be categorized in the Ehlers-Danlos syndrome Type III or the familial undifferentiated hypermobility group of disorders, but differed from these conditions by virtue of the severity of articular complications and the presence of wormian bones in the skulls. We consider that these patients have an undelineated connective tissue disorder; attempts at characterization at the molecular level are underway.

Although Hirschsprung's disease is a relatively common congenital malformation, with an estimated incidence of about 1:5000, Primary Central Hypoventilation Syndrome (Ondine's curse) is exceedingly rare, with about 50 reported cases. We describe a patient with total colonic aganglionosis occurring together with failure of automatic control of respiration, specific facial dysmorphology and characteristic CT scan changes to substantiate further the syndromic nature of this association.

Hereditary spastic paraplegia (HSP) is rarely inherited in an X-linked recessive mode in pure and complicated forms. Recently, molecular linkage studies have suggested that these variant X-linked HSP conditions result from locus heterogeneity. In this paper we report on the clinical and linkage analysis of a kindred with complicated X-linked HSP. The finding in this family of a map location of the putative HSP gene in the same region as the documented for the pure HSP gene provides evidence that allelic mutations might also be responsible for the variable phenotype encountered in these X-linked disorders.