Sorsby's fundus dystrophy is genetically linked to chromosome 22q13-qter.

Sorsby's fundus dystrophy (SFD) is an autosomal dominant macular degeneration developing in the third or fourth decade. Patients lose central vision from subretinal neovascularization and atrophy of the choriocapillaris, pigment epithelium and retina. SFD shares some striking clinical features with age-related macular degeneration (AMD), the most common cause of blindness in western countries thereby providing a valuable genetic model for AMD. To map the SFD locus, we performed linkage analysis in a single large SFD family. After exclusion of approximately 65% of the autosomal genome, we found significant linkage to several markers from chromosome 22. Recombinant chromosomes sublocalize the SFD gene to 22q13-qter between D22S275 and D22S274.

Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm.

Huntington disease is associated with an unstable and expanded (CAG) trinucleotide repeat. We have analysed the CAG expansion in different tissues from 12 affected individuals. All tissues examined were found to display some repeat mosaicism, with the greatest levels detected in brain and sperm. Regions within the brain showing most obvious neuropathology, such as the basal ganglia and the cerebral cortex, displayed the greatest mosaicism, whereas the cerebellar cortex, which is seldom involved, displayed the lowest degree of CAG instability. In two cases of childhood onset disease we detected differences of 8 and 13 trinucleotides between the cerebellum and other regions of the brain. Our results provide evidence for tissue specific instability of the CAG repeat, with the largest CAG repeat lengths in affected regions of the brain.

Evaluation of the Idexx ProCyte Dx® for analysis of canine cerebrospinal fluid.

OBJECTIVES: To assess the utility of the Idexx ProCyte Dx® haematology analyser for assessing total nucleated cell count and differential cell counts in canine cerebrospinal fluid. MATERIALS AND METHODS: Seventy-three client-owned dogs undergoing investigations for pyrexia and/or neurological signs were prospectively included. Cerebrospinal fluid samples were assessed using an Idexx ProCyte Dx® analyser and the results were compared to those obtained with the external laboratory reference standard. RESULTS: The Idexx ProCyte Dx® performed with good sensitivity (92.6%) and moderate specificity (67.4%) for total nucleated cell count when compared to the reference standard. Qualitative assessment of the Idexx ProCyte Dx® scatter plots, and quantitative assessment of differential cell counts where available, appeared to correlate well with the external laboratory manual differential cell counts, with a good-to-high agreement in 25 of 26 samples (96.2%). CLINICAL SIGNIFICANCE: The Idexx ProCyte Dx® analyser performed well in determining the total nucleated cell count and differential cell counts in canine cerebrospinal fluid when compared to a reference standard of external laboratory analysis, except for cell counts higher than ~1000/µL. As the Idexx ProCyte Dx® currently only provides a cell count in 10 cells/µL increments, software modification may improve agreement between the two methods. As in human medicine, automated methods may prove useful in the future for cerebrospinal fluid analysis in addition to manual assessment, particularly in an emergency setting.

Association between the findings on magnetic resonance imaging screening for syringomyelia in asymptomatic Cavalier King Charles spaniels and observation of clinical signs consistent with syringomyelia in later life.

A questionnaire-based study was used to investigate the association between the findings on magnetic resonance imaging (MRI) screening for syringomyelia (SM) in 79 asymptomatic Cavalier King Charles spaniels (CKCS) and the subsequent development of clinical signs consistent with SM in later life. Owners reported clinical signs consistent with SM in 13/79 (16%) dogs at the time of the questionnaire. A significantly greater proportion of CKCS with a syrinx visible on MRI screening showed clinical signs in later life (9/25, 36%) than dogs without a visible syrinx (4/54, 7%; odds ratio 6.9). Whether the findings of MRI screening can be used to indicate the likelihood of an asymptomatic CKCS developing clinical signs consistent with SM in later life warrants further prospective study in a larger cohort of dogs.

Autosomal recessive microcephaly and micromelia in Cree Indians.

In a highly consanguineous, predominantly Cree Indian community in northern Saskatchewan, Canada, 14 similarly malformed babies have been born to eight different mothers since 1953. Six of these infants are reported to assist delineation of the syndrome. The major manifestations of the condition are: Intrauterine growth retardation, perinatal death, marked microcephaly, and severe malformations of the limbs, especially the arms. Elbows are fused, forearms are greatly shortened and usually contain only a single bone, and the hands are very abnormal with only two to four malformed digits. Parental consanguinity, a sex ratio close to one, and a 25% segregation ratio all support autosomal recessive inheritance of this syndrome.

Regional localization of an X-linked mental retardation gene to Xp21.1-Xp22.13 (MRX38).

A gene responsible for X-linked mental retardation with macrocephaly and seizures (MRX38) in a family with five affected males in three generations was localized to Xp21.1-p22.13 by linkage analysis. Recombination events placed the gene between DXS1226 distally and DXS1238 proximally, defining an interval of approximately 14 cM. A peak lod score of 2.71 was found with several loci in Xp21.1 (DXS992, DXS1236, DXS997, and DXS1036) at a recombination fraction of zero. The map intervals of 5 X-linked mental retardation loci, MRX2 (Xp22.1-p22.2), MRX19 (Xp22), MRX21 (Xp21.1-p22.3), MRX29 (Xp21.2-p22.1), and MRX32 (Xp21.2-p22.1), and two syndromal mental retardation loci, Partington syndrome (PRTS; Xp22) and Coffin-Lowry syndrome (CLS; Xp22.13-p22.2), overlap this region. As none of these display the same phenotype seen in the family reported here, this X-linked mental retardation locus may represent a new entity.

Monochorionic diamniotic minimally conjoined twins: a case report.

We present the second case of monochorionic diamniotic (MC/DA) conjoined twins. There was minimal conjunction, which was predominantly extrafetal and confined to the periumbilical ventral region. The omphalopagus twins, attached to a single forked umbilical cord, were connected by a shared umbilical hernia containing the ileum of twin B. The only visceral conjunction, located just within the belly of twin A, was midileal with the 2 separate ileums converging toward a short segment of shared muscularis propria and of side-to-side fistulization. Gastrointestinal and musculoskeletal anomalies were present in both twins with severe amyoplasia and arthrogryposis multiplex in twin A. Possible mechanisms underlying this unusual form of MZ twinning are discussed.

Atelosteogenesis type III: a distinct skeletal dysplasia with features overlapping atelosteogenesis and oto-palato-digital syndrome type II.

We present 5 cases of a short-limb dwarfism syndrome whose manifestations overlap those of atelosteogenesis and oto-palato-digital syndrome Type II. Clinical, radiographic, genetic, and histologic data are presented which demonstrate differences between our patients and previously reported cases of these other conditions. We conclude that the disorder seen in these children represents a distinct chondrodysplasia for which we propose the name atelosteogenesis Type III.

Exclusion of a brain lesion: is intravenous contrast administration required after normal precontrast magnetic resonance imaging?

BACKGROUND: No evidence-based guidelines are available for the administration of gadolinium-based contrast media to veterinary patients. OBJECTIVE: To investigate whether administration of intravenous (IV) contrast media alters the likelihood of identifying a brain lesion in dogs and cats. ANIMALS: Four hundred and eighty-seven client-owned animals referred for investigation of intracranial disease. METHODS: Two reviewers retrospectively analyzed precontrast transverse and sagittal T1-weighted (T1W), T2-weighted, and fluid-attenuated inversion recovery low-field MRI sequences from each patient for the presence of a clinically relevant brain lesion. All sequences subsequently were reviewed in the same manner with additional access to postcontrast T1W images. RESULTS: Of the 487 precontrast MRI studies, 312 were judged to be normal by 1 or both reviewers. Of these 312 studies, a previously undetected lesion was identified in only 6 cases (1.9%) based on changes observed on postcontrast sequences. Final diagnoses included meningoencephalitis of unknown origin (n = 1), feline infectious peritonitis (n = 1), and neoplasia (n = 2). All 4 of these cases had persistent neurological deficits suggestive of an underlying brain lesion. Contrast enhancement observed in the 2 other cases was considered falsely positive based on the results of further investigations. CONCLUSIONS AND CLINICAL IMPORTANCE: In patients with normal neurological examination and normal precontrast MRI, the subsequent administration of IV gadolinium-based contrast media is highly unlikely to disclose a previously unidentified lesion, calling into question the routine administration of contrast media to these patients. However, administration still should be considered in animals with persistent neurological deficits suggestive of an underlying inflammatory or neoplastic brain lesion.

The abdominal muscle deficiency triad syndrome--experience with ten cases.

The triad or "prune belly" syndrome comprising deficient abdominal muscles, megaloureters with gegacystis and undescended testes has been considered a fairly rare anomaly. The Canadian Province of Saskatchewan appears to have had an unusually high incidence of this condition and it was hoped that epidemiologic investigation of the ten most recent cases might contribute information about the basic etiology of the syndrome. It is suggested that a previously unreported association with monozygotic twinning, apparent in the presently reported series, along with the well-recognized almost exclusive limitation of the syndrome to males, may provide major clues in further investigations of this condition.

Gonadal dysgenesis with 45,X/46,X,dic(Yp) mosaicism.

A female patient with a gonodal mucinous cystadenoma on the right side and a gonadoblastoma on the left was found to be a 45,X/46,X,dic (Yp) mosaic. This brings the total number of cases with dicentric Y chromosome reported to date to 23. Together with the available evidence, the information derived from this case supports the hypothesis that the gene on the long arm of the Y chromosome is responsible for the initiation of testicular differentiation, whereas that on the short arm is responsible for the maturation of the testes.

Kyphomelic dysplasia: a rare form of semilethal skeletal dysplasia.

Kyphomelic dysplasia is a rare form of generalized skeletal dysplasia with about 15 cases described so far in the literature. We present the clinical, radiological, and pathological findings of an antenatally detected female fetus affected with this disorder. The differential diagnoses of prenatal and perinatal semilethal skeletal dysplasias and salient features of documented cases of kyphomelic dysplasia are presented.

Familial infantile cortical hyperostosis in a large Canadian family.

Infantile cortical hyperostosis is a rare proliferative bone disease affecting infants under the age of 6 months. In 1961 a large family of French-Canadian origin in which 14 children in three generations were affected was described. Since then 20 new cases have been found in this family. This is the largest familial aggregation of this disease reported in the literature to date. On the basis of the findings in this pedigree, the familial form of the disease appears to be transmitted by a single autosomal dominant gene with incomplete penetrance and variable expressivity.

Sorsby's fundus dystrophy.

Ever since Sorsby described his pseudoinflammatory dystrophy in five families, its characteristics have been unclear. The findings in ten affected members of a seven-generation pedigree are discussed and the literature is reviewed. Patients with this dominantly inherited fundus dystrophy lose central vision between the second and fourth decade of life. Three variations in the fundus appearances were distinguished: in the first and most common, white to yellow fundus spots (which are not drusen) accompany a disciform macular degeneration; in the second, the fundus spots are absent; in the third, the yellow deposits are associated with atrophic macular degeneration. Atrophy of the retina, pigment epithelium, and choroid then slowly progresses toward the periphery. Treatment does not halt the progress of the disease. Although variations in this dystrophy may be examples of genetic heterogeneity, Sorbsy's fundus dystrophy is a distinct clinical disorder.

A founder effect in three large Newfoundland families with a novel clinically variable spastic ataxia and supranuclear gaze palsy.

A distinctive slowly progressive neurodegenerative disorder, which falls under a new category of neurological diseases, the hereditary spastic ataxias (HSA), is described in three independently ascertained Newfoundland kindreds. HSA is a heterogeneous group of disorders in which pyramidal tract features overlap cerebellar characteristics. The families are assumed to have the same condition as, although apparently unrelated, all originate in a historically isolated cluster of rural communities and link to the same locus at 12p13, SAX1. Clinically the phenotype is very variable but lower limb hypertonicity and hyperreflexia are early and prominent generally preceded by eye movement abnormality, an impaired vertical downward saccade and a typical involuntary head jerk. These are followed by variable levels of ataxia, dysarthria, and dysphagia. Onset occurs in the first two decades and can be detected in most by early adulthood. Significant mobility problems are present by the fourth decade with a broad based ataxic and spastic gait. MRI scans of brain and spinal cord were normal. Neuropathology showed degeneration of corticospinal tracts and posterior columns and midbrain neuronal loss. The phenotype is striking in its diversity among and within families and the variability of expression can be observed within the same sibship. Pedigree analysis shows no evidence of anticipation or any sex differences in severity. The condition is unusually prevalent in the province of Newfoundland, which is characteristic of a founder effect followed by isolation and large family size. Fine mapping efforts have reduced the critical interval of the SAX1 locus to 1.9Mb. Identification of the SAX1 gene will help to clarify the pathogenesis of this type of HSA.