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We present a 17-year-old boy, diagnosed with tyrosinaemia type I at an age of 7 months, with new complaints of severe intermittent photophobia and burning eyes. His tyrosinaemia type I is treated with nitisinone and a protein-restricted diet. Dietary compliance is low since he entered puberty. His ocular complaints are attributable to subepithelial corneal deposits, resembling the common corneal phenotype of tyrosinaemia type II. Serum tyrosine levels were markedly elevated. Tyrosinaemia is a metabolic disease of tyrosine metabolism, subdivided into two types. Corneal deposits and photophobia are cardinal features of untreated tyrosinaemia type II, but not of type I. Novel treatment strategies (with nitisinone) for type I tyrosinaemia lead to a phenotype comparable with type II, including these corneal deposits. At follow-up visits his ocular complaints unfortunately remained unchanged, though he states his dietary compliance improved through the years.

Introduction: Neuroimaging of the brain in the diagnostic work-up of patients with neurodevelopmental disorders is a matter of continuing debate. Recommendations range from performing brain imaging in all patients with neurodevelopmental disorders to performing an MRI only in those with indication on clinical examinations. Important indications for neuroimaging are head size abnormalities and focal neurological findings., Methods: Patients with neurodevelopmental disorders of unknown origin (n = 410), referred to a specialized tertiary diagnostic center for neurodevelopmental disorders were included in a retrospective analysis. A 1-day work-up, including an MRI of the brain was performed. Studied were the: (i) yield of MRI scans of the brain and (ii) associations of specific clinical symptoms/signs with abnormal and diagnostic MRI scans., Results: (i) In 30.7% of the 410 patients with neurodevelopmental disorders (n = 126), abnormal MRI scans were observed, leading to an etiological diagnosis in 5.4% of the patients (n = 22). (ii) Pyramidal disorders (P = 0.001), epilepsy (P = 0.04) and an abnormal head circumference (P = 0.02) were associated with an abnormal MRI scan. The presence of one of the following neurological symptoms/signs: movement disorders, pyramidal disorders, epilepsy, or an abnormal head circumference was associated with a diagnostic MRI scan (P < 0.001) (diagnostic MRI % in neurological versus no neurological symptoms/signs, 13.0% versus 1.9%)., Conclusion: Neuroimaging of the brain in a tertiary care center for patients with neurodevelopmental disorders of unknown origin is useful, especially in case of neurological symptoms/signs.

Purpose of Review: Visual field defects (VFDs) produced by temporal lobe resections provide valuable information on the retinotopic organization of the optic radiations. The results of this systematic review of the literature will be translated into a revised--and evidence-based--map of the retinotopic anatomy of the anterior optic radiations., Recent Findings: Recent studies provide best evidence by combining automatic static perimetry and modern imaging techniques. VFDs occur in 83% of patients undergoing temporal lobectomy. There is a significant correlation between size of resection and amount of VFD. Most defects appear incongruous. Macular involvement is seen in more than 50% of cases. The inferolateral defect border is of a sloping nature and sometimes crosses the horizontal meridian. On the basis of these findings, the classical theory on the retinotopic anatomy of the optic radiation should be revised., Summary: This article systematically reviews the literature on VFDs after temporal lobe resection. Frequency, size, congruity, macular involvement and defect borders are related to size of resection. The classical theory on the retinotopic organization of the anterior optic radiations should be revised.

Objective: Infantile esotropia, a common form of strabismus, is treated either by bilateral recession (BR) or by unilateral recession-resection (RR). Differences in degree of alignment achieved by these two procedures have not previously been examined in a randomised controlled trial., Design: Controlled, randomised multicentre trial., Setting: 12 university clinics., Participants and Intervention: 124 patients were randomly assigned to either BR or RR. Standardised protocol prescribed that the total relocation of the muscles, in millimetres, was calculated by dividing the preoperative latent angle of strabismus at distance, in degrees, by 1.6., Main Outcome Measure: Alignment assessed as the variation of the postoperative angle of strabismus during alternating cover., Results: The mean preoperative latent angle of strabismus at distance fixation was +17.2 degrees (SD 4.4) for BR and +17.5 degrees (4.0) for RR. The mean postoperative angle of strabismus at distance was +2.3 degrees (5.1) for BR and +2.9 degrees (3.5) for RR (p = 0.46 for reduction in the angle and p = 0.22 for the within-group variation). The mean reduction in the angle of strabismus was 1.41 degrees (0.45) per millimetre of muscle relocation for RR and 1.47 (0.50) for BR (p = 0.50 for reduction in the angle). Alignment was associated with postoperative binocular vision (p = 0.001) in both groups., Conclusions: No statistically significant difference was found between BR and RR as surgery for infantile esotropia.

Purpose: To study the ocular phenotype of Pierson syndrome and to increase awareness among ophthalmologists of the diagnostic features of this condition., Design: Retrospective, observational case series., Methods: A multicenter study of 17 patients with molecularly confirmed Pierson syndrome. The eye findings were reviewed and compared to pertinent findings from the literature., Results: The most characteristic ocular anomaly was microcoria. A wide range of additional abnormalities were found, including posterior embryotoxon, megalocornea, iris hypoplasia, cataract, abnormal lens shape, posterior lenticonus, persistent fetal vasculature, retinal detachment, variable axial lengths, and glaucoma. There was high interocular and intrafamilial variability., Conclusions: Loss-of-function mutations in laminin beta2 (LAMB2) cause a broad range of ocular pathology, emphasizing the importance of laminin beta2 in eye development. Patients with Pierson syndrome can initially present with ocular signs alone. In newborns with marked bilateral microcoria, Pierson syndrome should be considered and renal function investigated.

Joubert syndrome (JBS) is a clinically variable and genetically heterogeneous developmental brain disorder with autosomal recessive inheritance. Five genes, AHI1, NPHP1, CEP290, MKS3, and RPGRIP1L, and two additional loci on chromosome 9 and 11 have been identified so far. The relative contributions of AHI1 mutations and NPHP1 deletions have not yet been determined in a population-based JBS patient cohort. We therefore undertook a nationwide survey of JBS in the Netherlands and performed DNA analysis of the AHI1 and NPHP1 genes, as well as a new candidate gene CYCLIN D1. We obtained clinical data and DNA samples of 25 Dutch JBS patients. DNA analysis of AHI1 revealed pathogenic homozygous or compound heterozygous AHI1 mutations in four patients (16%). Based on the birth prevalence of about 1 in 100,000 for JBS in the Netherlands, we estimated a carrier frequency of AHI1 mutations of approximately 1 in 400. In another two patients, the AHI1 mutation Arg830Trp was identified (homozygously and heterozygously), a possible low penetrance allele. No deletions of NPHP1 or CYCLIN D1 mutations were detected in these 25 patients. In the four patients with AHI1 mutations, retinal disease (Leber congenital amaurosis or retinal dystrophy) was present in two, whereas none had renal disease. Pooling our data and data from the literature, retinal disease seems to occur in 75% of AHI1-associated JBS patients. Renal disease is present in 10% at most. We conclude that AHI1 mutations are an important cause of JBS in Dutch patients, and should always be looked for in patients suspected of JBS, especially when retinal dystrophy is present. Patients with AHI1 mutations should be regularly checked for retinal and renal disease up until adolescence.

Purpose: To assess motor and mental development before and after strabismus surgery in children with infantile esotropia., Patients and Methods: Mental and motor development indexes of 20 children with infantile esotropia without neurologic abnormalities and 17 age-matched healthy control subjects were prospectively tested at regular intervals before and after strabismus surgery with the Dutch version of the Bayley and ordinal scales of infant development., Results: The mean age for surgery in the study group was 13.5 months. Before strabismus surgery, the Bayley scales of infant development showed a significant delay in both mental (P < .045) and motor (P < .008) development for children with infantile esotropia compared with the control group. Three weeks after surgery, the delay in mental development had disappeared. The delay in motor development persisted for months. Two of the 7 ordinal scales--object permanence (P < .01) and means-end (P < .036)--showed a statistically significant delay for children with infantile esotropia. Three weeks after strabismus surgery, there was no difference between the study group and the control group., Conclusions: Children with infantile esotropia had delayed motor and mental development compared with healthy children. After strabismus surgery, patients recovered mentally, but their motor delays persisted for months when tested with the Bayley scales of infant development.

Oculodentodigital dysplasia (ODDD) is a rare, autosomal dominant pleiotropic disorder, caused by mutations in the Connexin 43 (Cx43 or GJA1) gene. Described here is the case of a 10-year-old girl with enamel hypoplasia, typical facies and mental delay, initially thought to be related to an unknown metabolic disorder. Careful clinical re-evaluation revealed a type of ODDD, characterised by the predominance of facial and ophthalmological involvement with mandibular retrognathism, and by the absence of cutaneous hand or foot syndactyly. A novel single-sequence variation (Nt460A>G) in exon 2, resulting in the substitution of alanine for threonine at amino acid 154, was found. These findings confirm once again the highly variable phenotypic expression caused by Cx43 mutations.

Purpose: Linkage intervals for erosive vitreoretinopathy (ERVR) and Wagner disease previously were found to overlap at 5q14.3. In a Japanese family with Wagner disease, a CSPG2/Versican splice site mutation (c.4004-2A-->G) was recently reported that resulted in a 39-nucleotide exon 8 in-frame deletion. We investigated whether CSPG2/Versican was mutated in six Dutch families and one Chinese family with Wagner disease and in a family with ERVR., Methods: In all families, extensive ophthalmic examinations, haplotype analysis of the 5q14.3 region, and sequence analysis of CSPG2/Versican were performed. The effects of splice site mutations were assessed by reverse transcription-polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR (QPCR)., Results: Three novel intron 7 sequence variants (c.4004-5T-->C, c.4004-5T-->A, c.4004-1G-->A) were identified in seven families. The c.4004-5T-->C variant was identified in four families with Wagner disease and a family with ERVR. The families were shown to carry the same 5q14.3 haplotype, strongly suggesting that this is a common Dutch founder variant. All three changes segregated with the disease in the respective families and were absent in 250 healthy individuals. In patients with the c.4004-5T-->A and c.4004-1G-->A variants, RT-PCR analysis of CSPG2/Versican showed activation of a cryptic splice site resulting in a 39-nt exon 8 in-frame deletion in splice variant V0. QPCR revealed a highly significant (P < 0.0001) and consistent increase of the V2 (>38-fold) and V3 (>12-fold) splice variants in all patients with intron 7 nucleotide changes and in a Chinese Wagner disease family, in which the genetic defect remains to be found., Conclusions: Wagner disease and ERVR are allelic disorders. Seven of the eight families exhibit a variant in intron 7 of CSPG2/Versican. The conspicuous clustering of sequence variants in the splice acceptor site of intron 7 and the consistent upregulation of the V2 and V3 isoforms strongly suggest that Wagner disease and ERVR may belong to a largely overlooked group of diseases that are caused by mRNA isoform balance shifts, representing a novel disease mechanism.

Three neonates, all girls, were presented immediately after birth with severe hypotonia. Two of them needed artificial ventilation because of respiratory insufficiency. All three pregnancies had been complicated by reduced fetal movements and moderate cerebral ventricular dilatation and in two of the three there was also polyhydramnios and congenital talipes. In all three infants congenital myotonic dystrophy was suspected after diagnosing myotonia in the mother. This was done by observing that none of the mothers were unable to release their grip immediately on command after shaking hands. Ophthalmological examination of the women revealed polychromatic lens crystals characteristic of myotonic dystrophy. Congenital myotonic dystrophy was confirmed by DNA analysis, as well as myotonic dystrophy in the mothers. All had an expansion of the number of cytosine-thymine-guanine(CTG)-trinucleotides in a part of the myotonic dystrophy protein-kinase gene. The first two infants died after 2 days and 15 months respectively.

Spinocerebellar ataxia type 7 (SCA7) represents a very rare and severe autosomal dominantly inherited cerebellar ataxia (ADCA). It belongs to the group of CAG-repeat or polyglutamine diseases with its underlying molecular genetical defect on chromosome 3p12-p21.1. Here, we performed a systematic study of the neuropathology on unconventional thick serial sections of the first available brain tissue of a genetically confirmed late-onset SCA7 patient with a very short CAG-repeat expansion. Along with myelin pallor of a variety of central nervous fiber tracts, we observed i) neurodegeneration in select areas of the cerebral cortex, and ii) widespread nerve cell loss in the cerebellum, thalamus, nuclei of the basal ganglia, and brainstem. In addition, upon immunocytochemical analysis using the anti-polyglutamine antibody 1C2, immunopositive neuronal intranuclear inclusions bodies (NI) were observed in all cerebellar regions, in all parts of the cerebral cortex, and in telencephalic and brainstem nuclei, irrespective of whether they underwent neurodegeneration. These novel findings provide explanations for a variety of clinical symptoms and paraclinical findings of both our and other SCA7 patients. Finally, our immunocytochemical analysis confirms previous studies which described the presence of NI in obviously degenerated brain and retinal regions as well as in apparently well-preserved brain regions and retina of SCA7 patients.

Introduction: Deficient postural control is one of the key problems in cerebral palsy (CP). Little, however, is known about the specific nature of postural problems of children with CP, nor of the relation between abnormal posture and dysfunction of the visual system., Aim of the Study: To provide additional information on the association of abnormalities in postural control and visual dysfunction of the anterior or posterior part of the visual system., Methods: Data resulting from ophthalmologic, orthoptic, neurological, neuro-radiological, and ethological investigations of more than 313 neurologically impaired children were retrospectively analyzed., Results: Abnormal postural control related to ocular and ocular motor disorders consisted of anomalous head control and subsequent abnormal head posture and torticollis. The abnormal postural control related to retrochiasmatical damage of the visual system consisted of a torticollis combined with adjustment of the upper part of the body, as if at the same time adapting to a combination of defects and optimizing residual visual functions., Conclusion: Visual dysfunctions play a distinct role in the postural control of children with CP.

Retinitis pigmentosa can occur as a complication of mevalonate kinase deficiency. This may be due to the unique isoprenoid metabolism in the retina. Early detection requires awareness on the part of the treating physician.

Children with perinatally acquired parenchymal haemorrhage are thought to have better visual perceptual skills than those with leukomalacia. We examined seven prematurely born children with parenchymal haemorrhage and 14 with grades 2-4 leukomalacia, at the age of 5 years. Clinical and magnetic resonance imaging parameters were related to visual perceptual performance assessed with the L94, using performance age. Belonging to the leukomalacia group, the inability to walk, a diminished peritrigonal white matter, a high degree of gliosis and cortical damage were associated with poorer visuo-perceptual skills. Enlarged lateral ventricles, confirming the findings of Melhelm (Radiology 214 (2000) 199), were associated with both cognitive, perceptual and motor problems and probably reflect the considerable extent of the brain damage. Specific factors protecting against visual perceptual impairment were a preserved volume of the right optical radiation and of the splenium of the corpus callosum. Children with leukomalacia are at considerable risk of visual perceptual impairment. Children with right-sided parenchymal haemorrhages also appear to be at risk although they function much better due to better motor and cognitive skills.

Objective: To assess the results of lacrimal duct probing in young children with epiphora, due to a congenital nasolacrimal duct obstruction., Design: Retrospective, descriptive., Method: Data were collected from medical dossiers on the results of lacrimal duct probing in children (0-48 months) with epiphora that was done in the period from January 1, 1997 to December 31, 2001 at the University Medical Centre in Utrecht, the Netherlands. The percentage of eyes that showed complete resolution of symptoms three months after the final probing was calculated., Results: Of the 89 children who had undergone lacrimal duct probing, seven were excluded and in three children (six eyes) the data could not be retrieved. In 96 of the remaining 116 eyes (83%), the symptoms disappeared: this included 96% of the age group 0-12 months (n = 25), 85% of the 13-24 months-olds (n = 55), 77% of the 25-36 months-olds (n = 22) and 57% of the 37-48 months-olds (n = 14). No complications of probing were seen., Conclusion: In most children in the various age groups, epiphora disappeared. Thus, children do not need to be probed in the first year of life out of fear of failure at an older age. Whether or not probing shortens the duration of epiphora cannot be determined on the basis of either this study or the literature.

This paper presents a patient with the following malformations: split hand and split foot on the left side, a hypoplastic fifth ray of the right hand and a hypoplastic first ray of the right foot with a small cleft between the first and second ray; eye abnormalities which consist of a complete iris coloboma of the left eye in an atypical position (cranio-temporal) and a coloboma of the choroid in the right eye; a glandular hypospadias and terato-zoospermia. Since split hand/split foot can be caused by mutations in the p63 gene, mutation analysis of this gene was performed. However, sequencing analysis did not reveal a mutation. This malformation complex may represent a new syndrome.

To determine predictive values of early visual and neurocognitive assessment in children with perinatally acquired haemorrhagic or ischaemic brain lesions selected on the basis of ultrasound, 63 children (37 boys, 26 girls), who had been followed and examined until the age of 18 months, were reexamined at 5 1/2 years. Good correlations between visual and neurodevelopmental assessments at 18 months and at 5 1/2 years were found. When ultrasound abnormalities were combined with early visual and neurocognitive assessment data, good predictive values, especially for the group of children who had grade 2 to 4 leukomalacia, were found for visual acuity and neurodevelopment.

Background/aims: Visual functions of neurologically impaired children with permanent cerebral visual impairment (CVI) can be difficult to determine. This study investigated the behavioural profile of CVI children by means of ethological observations in order to gain a better understanding of their visual functions., Methods: Video registrations of nine subjects who were unable to undergo more orthodox methods of visual function testing were observed and analysed by an ethologist., Results: A series of behaviours (direct signs) and supportive or confirming behavioural elements (indirect signs) indicating some visual perception in the children were found., Conclusion: Detailed ethological observations of visual behaviour were shown to be useful for analysing visual functions of children with permanent CVI.

This study reports on the findings of longitudinal follow-up of visual function in a 12-year-old girl affected by congenital right hemihydranencephaly. This extremely rare unilateral brain malformation allowed the authors to gather new information on neuronal plasticity and functional compensations of the visual system across a period of 10 years. An extension of the preserved right visual hemifields above the middle line and strategical eye or head positions developed to increase visual functions are discussed. In addition, ophthalmological and orthoptical findings, as well as the development of monocular grating and linear acuity, are described.

Von Hippel-Lindau disease (VHL) is an autosomal dominant tumour syndrome caused by germline mutations of the VHL tumour suppressor gene located on chromosome 3p25-26. In VHL tumours may occur in 14 different target organs, including the eye. Retinal angiomas are considered the first manifestation of VHL disease in 43% of cases, and the cumulative probability of developing a retinal angioma in one or both eyes rises during each decade of life, reaching 80% for patients over 80 years old. Since 1976 patients with VHL at the University Hospital of Utrecht and their at-risk relatives have been screened periodically by a multidisciplinary team. Long-term follow-up ophthalmological data were analysed with special attention to natural course and results of treatment. In addition, we looked for a genotype-phenotype correlation. Retinal angiomas were found in all families. In one large family with a missense mutation (V170D) of the VHL gene, in which the complete spectrum of visceral- and central nervous system (CNS) features of VHL is present, macular, parapapillary, optic disc and ora serrata angiomas were also found. In general, however, a clear-cut genotype-phenotype correlation could not be found. Only early detection and treatment of peripheral retinal angiomas can be expected to decrease the percentage of patients with decreased visual acuity. Therefore, early detection and treatment of these tumours is of paramount importance. Ophthalmological screening of patients and persons at risk should start as early as possible. In patients with apparently sporadic retinal angiomas it is advisable to perform germline DNA analysis, since the risk of developing VHL is high, especially if the angiomas are bilateral, or unilateral and multifocal, if the patient is young, or if there is a family history suggestive of VHL.

Purpose: To analyse the natural course of visual acuity in subjects affected by cerebral palsy., Methods: During the past 5 years, 16 children underwent repeated grating acuity measurements using the acuity card procedure. At the end of the follow-up final grating acuity was compared with linear acuity obtained using standard optotypes., Results: A good or moderate improvement in grating acuity was shown by 14 subjects. However, the general development of grating acuity showed a protracted course and early values did not correlate with final grating acuity (r = 0.20). Moreover, most of the children showed subnormal vision when measured with standard optotypes., Conclusion: Clinicians should remain optimistic about the potential for some visual development in children affected by cerebral palsy. However, great caution should be exercised in extrapolating information from early grating acuity measurements. Regular assessments with the acuity card procedure are necessary in order to gain an insight into the natural course of visual development in children affected by cerebral palsy.

Background: Von Hippel Lindau disease (VHL) is a rare autosomal dominant inherited disorder characterized by highly vascularized tumors in various organs. The abundant presence of endothelial cells in VHL tumors strongly suggest a role of the VHL tumor suppressor gene in the regulation of angiogenesis. Recently, in vitro studies have shown that the VHL tumor suppressor gene regulates the expression of vascular endothelial growth factor (VEGF). We investigated whether VHL patiens have increased levels of VEGF in their body fluids., Patients and Methods: The concentration of VEGF was measured in fluid of the anterior chamber of the eye, serum, urine, and fluid from renal cysts of VHL patients and unaffected individuals by ELISA. In addition, levels of basic fibroblast growth factor (bFGF), interleukin-8 (IL-8) and endothelin-1 (ET-1) were measured in urine and serum of VHL patients and control subjects., Results: In 80% of the VHL patients VEGF was detectable in aqueous fluid of the anterior chamber of their eyes. A strong positive correlation (r = 0.90) was found between the age of VHL patients and ocular VEGF concentrations. At comparable age, VEGF levels in ocular fluid of VHL patients were significantly higher (P < 0.001) than in unaffected subjects. No correlation was found between VEGF concentration and the presence of retinal angiomas. A 10 and 16 fold increase of VEGF concentration was seen in fluid from two independent VHL-related cysts as compared with VEGF serum levels of the same patient. The mean concentration of VEGF in serum of VHL patients (n = 15) (319 +/- 84 pg/ml) was higher than in matched controls (238 +/- 68 pg/ml; P = NS). The mean concentration of VEGF in urine of VHL patients (128 +/- 36 pg/ml) was lower than in matched controls (183 +/- 25 pg/ml; P = NS). Concentrations of VEGF did not correlate with the presence of VHL-related tumors. No differences were observed between concentrations of bFGF, IL-8 and ET-1 in serum and urine of VHL patients and matched controls., Conclusions: These findings support a role for the VHL tumor suppressor gene in the in vivo regulation of VEGF.

Background: Long chain 3-hydroxyacyl-CoA-dehydrogenase (LCHAD) is one of the enzymes involved in the breakdown of fatty acids. A deficiency of this enzyme is associated with life threatening episodes of hypoketotic hypoglycaemia during prolonged fasting. Neuropathy and retinopigmentary changes were mentioned in only a few cases., Methods: The case histories of two girls, aged 8 and 15 years, with LCHAD deficiency are reported., Results: Both children with LCHAD deficiency exhibited extensive macular pigmentary depositions and a 'salt and pepper' scattering of pigment in their retinas. The patients have decreasing visual acuity., Conclusion: The early recognition of LCHAD deficiency can increase the life expectancy in these patients through avoiding catabolism and through appropriate diets. Patients tend to be free of symptoms between attacks, however. Testing for the disorder, therefore, should be included in the diagnostic process for children with retinal dystrophy, in particular when other clinical symptoms are known to have occurred.

To assess the effect of surfactant replacement therapy (SRT) on the prevalence and severity of retinopathy of prematurity (ROP), we compared data from 160 SRT-treated preterm infants with data from 230 historic controls. The prevalence of ROP was 30.6% in the treatment group and 23.4% in the control group. Severe ROP (stages 3-4) was seen in 6.1% of the infants with ROP in the treatment group and 20.3% of the ROP patients in the control group. Surfactant therapy had no influence on the prevalence of ROP (odds ratio 1.4, 95% confidence interval 0.797-2.459, p = 0.242). However, SRT was associated with a decreased risk for severe ROP, compared to mild ROP (odds ratio 0.226, 95% confidence interval 0.056-0.905, p = 0.036). These data suggest that SRT is associated with a decreased risk for severe ROP.

Three siblings from a consanguineous marriage were found to have a cleft lip. Two of them developed a progressive retinopathy which was identified as a cone-rod dystrophy. It is suggested that this association may represent a hitherto unreported entity with an autosomal recessive pattern of inheritance, although chance co-occurrence cannot be excluded.

Early detection of retinopathy of prematurity (ROP) in premature and very-low-birth-weight infants is crucial. In this retrospective study, 581 infants either with a birth weight below 1500 g or a gestational age of less than 32 weeks, or who did not fit these criteria but were judged to be at increased risk, were screened for ROP. ROP developed in 159 (27.4%). The incidence of ROP appeared to be inversely proportional to birth weight and gestational age. Infants with a birth weight below 750 g had a significantly higher risk of developing stage 3 and 4 ROP. The mean age at detection was 7.6 +/- 1.6 weeks. Nearly all of the ROP cases and all of the stage 3 and 4 cases were detected between the 5th and 10th week. Because screening should be focused on these vision-threatening stages, ophthalmic examinations should be concentrated in, but not limited to, the period between the 5th and the 10th postnatal week.

Charcot-Marie-Tooth disease comprises a heterogeneous group of neurologic disorders that shape peripheral motor and sensory neuropathy. A classification of these disorders was proposed in 1975, defining seven types of hereditary motor and sensory neuropathy. Clinical features of hereditary motor and sensory neuropathy type VI are muscle weakness and atrophy in leg and hand muscles, leading to progressive disability and loss of vision and progressing to blindness due to optic atrophy. Hereditary motor and sensory neuropathy type VI was first reported in 1879 by Vizioli, who described a kinship in which a father and two sons presented with peroneal muscular atrophy in association with optic atrophy. Since then, at least nine similar cases have been reported: three sporadic cases, two pairs of siblings who were offspring of consanguineous parents, and one pair of siblings who were offspring of unrelated parents suggesting autosomal recessive inheritance. Vertical transmission has been reported only by Vizioli. We present a father and two offspring (one boy and one girl) with the above-mentioned characteristic features of hereditary motor and sensory neuropathy type VI. Vizioli's kinship and either an autosomal recessive or autosomal dominant pattern of inheritance.

We report four children (three sibs and one sporadic case) with congenital sutural cataract (opacity of the sutures of the crystalline lens), retinitis pigmentosa (leading to diminished visual acuity), microcephaly, and moderate to severe psychomotor retardation. The three sibs (two F and one M) were born to healthy, consanguineous Moroccan parents; the sporadic case is an 11-year-old Dutch girl who presented at the age of nine months with a small head circumference (third percentile) and sutural cataract. Psychomotor development was retarded in all cases, retinitis pigmentosa became evident during middle or late childhood. Congenital cataract has been described in association with a large number of various congenital abnormalities, such as renal, nervous system, skeletal, dermal and ocular (including retinal) defects. A computer-assisted literature search has not revealed similar cases to those presented here. The cases described here appear to have a previously undescribed combination of ophthalmological and cerebral abnormalities. The inheritance of the condition appears to be autosomal recessive as a brother and two sisters (offspring of normal consanguineous parents) are affected. The differential diagnosis is discussed.

Unlabelled: Von Hippel-Lindau disease is an autosomal dominant inherited disorder causing hemangioblastomas of the central nervous system (CNS), retinal hemangiomas, renal cell carcinomas, pheochromocytomas, pancreatic and liver cysts, and epididymal cystadenomas., Purpose: Since 1976, we have periodically screened for the lesions in a large affected family and were able to evaluate new strategies in detection and treatment., Patients and Methods: A total of 23 individuals underwent the screening program. A multidisciplinary team of physicians was involved., Results: In 13 patients (7 females and 6 males), a total of 31 tumors was detected; hemangioblastoma of the CNS (9), retinal angioma (4), renal involvement (8), pheochromocytoma (4), pancreatic lesions (4), and liver lesions (2) were diagnosed by periodic family screening. On the basis of more than 10 years of experience and current literature, new criteria for diagnosis and treatment have been proposed., Conclusion: The von Hippel-Lindau disease gene appears to be a tumor suppressor gene, and its absence or a defect in its structure is responsible for the predisposition to the disease. Tumor development depends on a somatic second mutation in the homologous allele. That means, in disease-gene carriers, tumor growth may begin at any age. Most of the lesions can be treated successfully when diagnosed in time. Periodic screening by a multidisciplinary team has to be continued lifelong.

We documented the prevalence of retinopathy of prematurity (ROP) in a group of 46 infants suffering from a moderate or severe respiratory distress syndrome and treated with surfactant replacement therapy (SRT) and 61 controls admitted in the year prior to the institution of SRT. Mortality in the treatment group was lower than in the control group (15.5% versus 23.8; P = 0.29). The ROP prevalence in the treatment group was 47.8% and in the control group 27.9%. To analyse the contribution of SRT alone to the prevalence of ROP, multivariate analysis using logistic regression technique was used. The odds ratio for SRT was 5.2 with a 95% confidence interval of 1.3-20.7, P = 0.02. The prevalence of severe ROP in the surfactant treated group was not increased compared to the control group. From our data we conclude that SRT increases the risk of developing ROP but is not associated with more severe forms of ROP.

Peters'-Plus syndrome is characterized by Peters' anomaly, a typical face, cleft lip and palate, short limb dwarfism, and developmental retardation. We report the follow-up of six patients in the original report, 10 yet unreported patients, and review 26 patients that have been reported in the literature. The spectrum of the syndrome is broadened by data from affected sibs which indicate that a wider range of anterior chamber cleavage disorders may be present, a cleft lip or palate need not be present, and developmental retardation may be mild or even absent. An increased foetal loss in families with Peters'-Plus syndrome may indicate intrauterine death of some foetuses affected by the syndrome. The pattern of inheritance is autosomal recessive.

A father and two sons with blepharophimosis, ptosis, polythelia and brachydactyly are presented, apparently without other abnormalities. The features do not fit into any previously described syndrome. This condition may represent a hitherto undescribed syndrome, although resemblance with the blepharophimosis-ptosis-epicanthus inversus syndrome exists. Inheritance is probably autosomal dominant.

Diagnosing and monitoring of Graves' Orbitopathy (GO) can be supported by use of Ultrasonography (USG) and Computerized Tomography (CT); they provide supplementary information. In this retrospective study we describe 107 clinical GO patients evaluated by B-scan USG and 27 clinical GO patients evaluated by CT scan. Analysis of 236 B-scan USG included measurements of medial, inferior and lateral rectus muscles. The presence of muscle enlargement and increased orbital fat were noted by the radiologist on 27 CT scans. Sensitivity of both B-scan USG and CT scan were calculated. We suggest that B-scan USG has a high sensitivity, which is equal or better than CT scan sensitivity in diagnosing GO. Furthermore USG A and B scan combination is an effective, accurate tool in diagnosing GO, and optic neuropathy, but it also provides essential information about the GO disease activity.

Assessment of visual acuity using the visual acuity card procedure in 164 children with cerebral palsy revealed low visual acuity in 71 per cent. Results of ophthalmological examination were available for 74 of these patients, but could not explain adequately the low visual acuity of 36 of the 43 patients (84 per cent) assessed by both the acuity card procedure and other techniques. There is a high probability that cerebral visual disturbance is present in these patients. Awareness of visual disability when compiling a programme of visual and neurodevelopmental stimulation for children with cerebral palsy is essential.

Keratosis follicularis spinulosa decalvans (KFSD) is a rare X-chromosomal disorder. It consists of follicular hyperkeratosis of the skin, scarring alopecia of the scalp, absence of the eyebrows, and corneal degeneration. There is photophobia in childhood, but the symptoms tend to diminish after puberty, and prognosis for vision is good. Some heterozygotes do show clinical symptoms. In a large Dutch pedigree we performed DNA analysis in order to localize the KFSD gene. In 54 individuals, including 21 affected males, RFLP analysis was done using DNA probes covering the X chromosome. Two-point linkage analyses with 19 informative DNA markers revealed significant linkage to DNA probes on Xp21.1-p22.3. The highest lod scores of 5.70 and 4.38 were obtained with DXS41 and DXS16 at a recombination fraction of zero and 4 cM, respectively. Multipoint linkage data place KFSD between DXS16 and DXS269. Our data confirm X linkage of KFSD in this family and tentatively map the gene on Xp22.2-p21.2. Combined with clinical investigation, RFLP analysis may become an important tool in carrier detection.

In a large Dutch family with keratosis follicularis spinulosa decalvans (KFSD, MIM 308800), DNA linkage analysis was performed in order to locate the gene. Pedigree analysis and lod score calculation confirmed X-linked inheritance and revealed significant linkage to DNA markers on Xp. A maximum lod score of 5.70 at theta = 0.0 was obtained with DXS41 (p99.6). The KFSD gene is tentatively located on Xp21.2-p22.2.

Chandler's syndrome and essential progressive iris atrophy, we believe, are two entities of the same syndrome. We have presented a case which could be considered a perfect intermediate. The mechanical 'stretch' theory of Campbell et al., supported to an extent by the light and electron microscopic findings of Rodrigues et al., is untenable in view of the observation in our patient that the first, and broad, peripheral anterior synechia was opposite the position of the displacement of the pupil. Every case in which corneal abnormality, glaucoma and iris changes are found, should be checked explicitly, with specular microscopy and gonioscopy, for corneal endothelial changes and in order to locate the area of predilection of peripheral anterior synechiae.

The dystrophy originally described by Reis and Bücklers shows electron-microscopically 'rod-shaped bodies' in the region of Bowman's membrane that cannot be distinguished from the 'rod-shaped bodies' in the granular dystrophy. Some authors conclude from this finding that the dystrophy is a superficial variant of the granular dystrophy. Our findings indeed point to the fact that the keratocytes are the primary source of the opacities as is the case in the granular dystrophy. From the clinical, biomicroscopic and light-microscopic differences, however, it seems likely that both dystrophies will in future be shown to be due to different biochemical defects or that they are at least allelic forms of the same biochemical defect.

In the literature two types of anterior corneal dystrophy are referred to as Reis-Bücklers' dystrophy. These are the one originally described by Bücklers in 1949 and known by us as the geographical form, and a honeycomb form. On the basis of electron-microscopic findings the geographical form is considered by some authors today to be a superficial variant of the granular dystrophy (Groenouw I), while the honeycomb form is looked upon as the "true" Reis-Bücklers' dystrophy. However, there is no clinical resemblance between the honeycomb type and the dystrophy described by Bücklers. Clinically it is easy to distinguish the geographical and the honeycomb type, and this is important for the prognosis of a corneal graft. The present authors do not agree that the term granular dystrophy should include the dystrophy described by Bücklers. There is a lack of clarity concerning this type of dystrophy, and clinically it bears no resemblance to granular dystrophy. In the authors' opinion it would be preferable to speak of the geographical and the honeycomb form of Reis-Bücklers' dystrophy.

The dystrophy in 1961 described by Waardenburg and Jonkers in considered in the literature as a separate dystrophy by some authors and as an atypical form of granular dystrophy by others. That it is in fact the first description of, and synonymous with, the honeycomb dystrophy (Thiel and Behnke), in the English-language literature usually called Reis-Bücklers' dystrophy, was proven by reinvestigation of the family concerned.

Corneal buttons from 2 patients from unrelated families with granular dystrophy were examined by light and electron microscopy. An electron-dense substance was noted between the basal epithelial cells; polymorphic electron-dense deposits ('rod-shaped' bodies) could be demonstrated subepithelially, between the stromal lamellae and also within the cytoplasma of the keratocytes. Our findings give credence to the view of earlier authors that the keratocyte is the primary source of the abnormal material.

Corneal thickness increases with advancing age in patients with the honeycomb type of Reis-Bücklers' dystrophy, affecting visual acuity. A linear relationship is found between these parameters. Also, corneal sensitivity decreases with increasing corneal thickness. The latter may be an import factor in the decrease of ocular irritation later in life in these patients.

Corneal thickness in the affected members of 3 families with Meesmann's epithelial dystrophy was statistically significantly less than that of the nonaffected members and of their controls. From our data one could speculate that the stroma rather than the epithelium is the primary source of the dystrophy. The thinner the cornea, the more marked the expression of the epitheliopathy. The affected members of the 2 families that were large enough for a separate analysis showed a marked difference in expressivity of the epithelial disorder. In one family the epitheliopathy showed a stationary character, while in the other there was a progression in the density of the epithelial vesicles.