Iris heterochromia: variations in form, age changes, sex dimorphism]

On a sample of n = 25,346 individuals from Vienna (10,855 males, 14,491 females) the iris pigmentation has been typed by the author. In this sample 65 cases of different types of heterochromia were found. The frequency of the occurrence of the different types of this anomaly could be calculated for the first time. Neglecting age, sex, and type of heterochromia the total frequency amounts to 0.256 (males: 0.157; females: 0.37) %. The variants of heterochromia very from cases of total heterochromia to those of various size; in addition to it a number of special types could be observed. The localization of the heterochrome parts of the iris shows certain variations; mostly, however, it is seen in the lower half of the iris. The nasal part is concerned in only one case; the temporal region never. Thus, the partial heterochromia is characteristic by a marked dependency of its localization. The colour of heterochromia varies from 2 a-14 according to the Martin-Schultz standard set of coloured eyes. However, No. 9 (ca. 50%) and No. 7 (ca. 20%) were the most frequent colours. The age variations are considerable. 5/6 of all heterochromias were found between the age from 2-19 years. Finally, a marked sexual dimorphism was observed, as in females heterochromia is much more frequent than in males.     

Teaching cases: Heterochromia

Abstract: A patient was noted to have 2 different eye colours and miosis in her left eye. She ultimately received a diagnosis of congenital Horner syndrome. Determinants of eye colour and possible clinical significance are discussed.The case: A 35-year-old woman with a hypertensive emergency and confusion presented to the emergency department. Incidentally, we noted that she had 2 different coloured eyes (heterochomia) and miosis of her left eye (Figure 1). The patient reported that her eyes had been different colours since very early in her childhood.Open in a separate windowFigure 1: This 35-year-old woman had different coloured eyes since birth. The entire iris of her right eye is brown, and the iris of the left eye is greenish brown. Her left pupil is smaller than the right, which is consistent with the diagnosis of congenital Horner syndrome.Although some patients have pigment changes involving only 1 segment of the iris (segmental heterochromia or heterochromia iridium),¹ our patient''s entire iris was involved (complete heterochromia or heterochromia iridis). Heterochromia iridis is rare, affecting fewer than 200 000 people in the United States.² Although uncommon in humans, it is common in some breeds of cats, dogs and horses.Eye colour is determined by the concentration and distribution of melanin in the iris, with both genetic and physiologic factors affecting determination and maintenance of iris colour. Most human cases of heterochromia are sporadic and benign, and they occur without any detectable underlying abnormality. Congenital heterochromia occurs in a variety of syndromes, including Sturge–Weber syndrome, Waardenburg syndrome and Parry–Romberg syndrome (3Table 1Open in a separate windowDisruption of the sympathetic stimulation of the melanocytes in the superficial stroma of the iris (especially as a child) can lead to heterochromia. Horner syndrome from the unilateral impairment of sympathetic nerves leads to ptosis, miosis, a lag in pupil dilation, enopthalmos (the impression of a sunken eye) and facial anhidrosis (decreased sweating on 1 side of the face). Acquired heterochromia can occur in adults in rare cases as a result of acquired Horner syndrome. In contrast to patients with acquired Horner syndrome, patients with congenital Horner syndrome, such as our patient, often lack several features of the syndrome.In adults with acquired heterochromia and miosis, Fuchs heterochromic cyclitis and sympathetic heterochromia must be considered. Unilateral sympathetic nerve lesions such as paravertebral neurilemmoma and neuroblastoma should also be considered. Our patient''s clinical presentation was inconsistent with any of these causes. Sympathetic heterochromia was suspected but investigations, including urinary catecholamines and an MIBG (iodine-131-meta-iodobenzylguanidine) scan, did not reveal excess catecholamine secretion or a sympathetic tumour.The patient''s blood pressure was managed with appropriate medication, and she was ultimately discharged from our care with a reversal of her confusion. There was no further follow-up with regard to her eye colour.Habib Ur Rehman MBBS Department of Internal Medicine Regina General Hospital Qu''Appelle Health Region Regina, Sask.     

High-resolution studies in patients with aniridia-Wilms tumor association,Wilms tumor or related congenital abnormalities

Summary We attempted to determine wheter all cases of AWTA (anirida-Wilms tumor association) or any of the following groups of patients show 11p deletion: cases of Wilms tumor with congenital abnormalities other than aniridia, those without any congenital abnormalities, tumor itself in cases of Wilsm tumor without constitutional 11p deletion and cases of aniridia or hemihypertrophy without Wilms tumor. We studied a total of 29 index patients including five cases of AWTA, four cases of Wilms tumor with various congenital abnormalities, 16 cases of Wilms tumor without other abnormalities, three cases of aniridia in one of which Wilms tumor developed later and a case of hemihypertrophy.In all five cases of AWTA and in a case of aniridia who later developed Wilms tumor, 11p deletion involving the p13 band was detected. The mother of the latter also showed an identical 11p deletion. The common segment of deletion was the middle part of the p13. Two possible hypotheses on the mechanism through which Wilms tumor might develop were evaluated, based on the distribution of break points. All other cases, including five with tumor culture, showed a normal karyotype.     

Genome-wide association studies for iris pigmentation and heterochromia patterns in Large White pigs

Eye colour genetics have been extensively studied in humans since the rediscovery of Mendel’s laws. This trait was first interpreted using simplistic genetic models but soon it was realised that it is more complex. In this study, we analysed eye colour variability in a Large White pig population (n = 897) and report the results of GWASs based on several comparisons including pigs having four main eye colour categories (three with both pigmented eyes of different brown grades: pale, 17.9%; medium, 14.8%; and dark, 54.3%; another one with both eyes completely depigmented, 3.8%) and heterochromia patterns (heterochromia iridis – depigmented iris sectors in pigmented irises, 3.2%; heterochromia iridum – one whole eye iris of depigmented phenotype and the other eye with the iris completely pigmented, 5.9%). Pigs were genotyped with the Illumina PorcineSNP60 BeadChip and GEMMA was used for the association analyses. The results indicated that SLC45A2 (on chromosome 16, SSC16), EDNRB (SSC11) and KITLG (SSC5) affect the different grades of brown pigmentation of the eyes, the bilateral eye depigmentation defect and the heterochromia iridis defect recorded in this white pig population respectively. These genes are involved in several mechanisms affecting pigmentation. Significant associations for the eye depigmented patterns were also identified for SNPs on two SSC4 regions (including two candidate genes: NOTCH2 and PREX2) and on SSC6, SSC8 and SSC14 (including COL17A1 as candidate gene). This study provided useful information to understand eye pigmentation mechanisms, further valuing the pig as animal model to study complex phenotypes in humans.     

Chromosomal findings in fetuses with prenatally diagnosed cysts of the choroid plexus

Summary Choroid plexus cysts were diagnosed in 25 out of 823 fetuses with prenatally diagnosed abnormalities (growth retardation/malformations). Among these, 5 revealed a chromosomal disorder (4 cases with trisomy 18 and one case with a translocation trisomy 21). Additional abnormalities, such as growth retardation, holoprosencephaly, hydrocephalus and club foot, were found in 6 out of the 20 fetuses with no chromosomal abnormality. All fetuses with a chromosomal disorder revealed further typical prenatally recognizable abnormalities. Our observation indicates that prenatally diagnosed choroid plexus cysts should be considered as an indication for prenatal chromosomal diagnosis, although the risk of there being an underlying chromosomal disorder is low in cases with no additional abnormalities.     

A polydactylous strain of mice

Summary A highly inbred strain ofMus musculus is described in which 12% of the males and 18% of the females are polydactylous. This polydactyly is the only abnormality occurring in these mice. In most cases only the first digit (big toe) of the right hind foot is more or less duplicated, but the left foot and other toes may also be affected. Abnormal fathers transmit the peculiarity more often to their daughters than to their sons. This fact cannot be explained on a genetic basis, since for various reasons genetic differences between these mice cannot be assumed to exist. In general, polydactylous mice have an excess number of motor neurons innervating the foot in the spinal cord on the abnormal side. This may be the cause for polydactyly as is known to be inAmphibia.     

Waardenburg syndrome: A rare genetic disorder, a report of two cases

Waardenburg syndrome (WS) is a rare genetic disorder. Patients have heterochromia or eyes with iris of different color, increased inter-canthal distance, distopia canthorum, pigmentation anomalies, and varying degree of deafness. It usually follows autosomal dominant pattern. In this report, two cases have been discussed but no familial history of WS has been found. Counseling of the patient is necessary and cases of irreversible deafness have been treated.     

Wiedemann-Beckwith syndrome: presentation of clinical and cytogenetic data on 22 new cases and review of the literature

Summary The main features of Wiedemann-Beckwith syndrome (WBS) include macroglossia, abdominal wall defects, visceromegaly, gigantism, hypoglycemia, ear creases, nevus flammeus, and mid-face hypoplasia. Twenty-two cases of WBS were examined clinically and cytogenetically, and compared to 226 previously reported cases. Aspects of the clinical evaluations are discussed. All individuals examined were chromosomally normal with no evidence of 11p abnormality as has been reported recently. The relevance of a possible relationship between clinical findings, chromosome abnormalities, and genes present on 11p is discussed. Transmission of this condition is most consistent with autosomal dominant inheritance with incomplete penetrance.     

A case of bilateral tibial hemimelia type VIIa

Congenital absence of tibia is a rare anomaly, and may be total or partial, unilateral or bilateral. Total absence is more frequent than partial, unilateral absence occurs more often than bilateral, with right limb more commonly affected than the left. In partial defect, almost always the distal end of the bone is affected, and of the bilateral cases, there may be total absence on both sides, or total on one side and partial on the other. Males are slightly more commonly affected than the females. Though, the family history is usually negative for congenital abnormalities and other diseases, there is a considerable chance of occurrence of congenital defect of the tibia or of other abnormalities, in near or remote relatives. We report a case of newborn having bilateral tibial hemimelia type VIIa.     

Nomenclature of iris color

Heterochromia simplex (Streiff) or true heterochromia of the iris (H. vera, H. congenita) is the product of mosaic inheritance arising from variable expressivity of the parental characteristics. This is different from the "mixed iris", which shows a mixture of colours, in which the components are no longer distinguishable but form a new shade.     

A specific chromosomal abnormality in rhabdomyosarcoma

A specific chromosomal abnormality, t(2;13)(q35;q14), was discovered in five cases of advanced rhabdomyosarcoma. It was identified directly in cells that had metastasized from bone marrow in one patient and in xenografts derived from the tumors of four other patients. The translocation was not restricted by histologic subtype, but was found in cases classified as alveolar, undifferentiated, or embryonal. Cytogenetic hallmarks of gene amplification (double minute chromosomes and homogeneously staining regions) were apparent in three cases. Other frequent abnormalities included rearrangements of chromosomes lp and trisomy of chromosome 8. The absence of the t(2;13) in more than 100 cases of other pediatric solid tumors investigated in our laboratory indicates its specificity for rhabdomyosarcoma. These cytogenetic findings suggest directions for further investigation of the molecular events underlying the genesis of this tumor.     

Identification of somatic chromosomal abnormalities in hypothalamic hamartoma tissue at the GLI3 locus

Hypothalamic hamartomas (HH) are rare, benign congenital tumors associated with intractable epilepsy. Most cases are sporadic and nonsyndromic. Approximately 5% of HH cases are associated with Pallister-Hall syndrome (PHS), which is caused by haploinsufficiency of GLI3. We have investigated the possibility that HH pathogenesis in sporadic cases is due to a somatic (tumor-only) mutation in GLI3. We isolated genomic DNA from peripheral blood and surgically resected HH tissue in 55 patients with sporadic HH and intractable epilepsy. A genome-wide screen for loss of heterozygosity (LOH) and chromosomal abnormalities was performed with parallel analysis of blood and HH tissue with Affymetrix 10K SNP microarrays. Additionally, resequencing and fine mapping with SNP genotyping were completed for the GLI3 gene with comparisons between peripheral blood and HH tissue pairs. By analyzing chromosomal copy-number data for paired samples on the Affymetrix 10K array, we identified a somatic chromosomal abnormality on chromosome 7p in one HH tissue sample. Resequencing of GLI3 did not identify causative germline mutations but did identify LOH within the GLI3 gene in the HH tissue samples of three patients. Further genotyping of 28 SNPs within and surrounding GLI3 identified five additional patients exhibiting LOH. Together, these data provide evidence that the development of chromosomal abnormalities within GLI3 is associated with the pathogenesis of HH lesions in sporadic, nonsyndromic patients with HH and intractable epilepsy. Chromosomal abnormalities including the GLI3 locus were seen in 8 of 55 (15%) of the resected HH tissue samples. These somatic mutations appear to be highly variable.     

Incidence of numerical chromosome aberrations in meningioma tumors as revealed by fluorescence in situ hybridization using 10 chromosome-specific probes

OBJECTIVE: Although information on the cytogenetic characteristics of meningioma tumors has accumulated progressively over the past few decades, information on the genetic heterogeneity of meningiomas is still scanty. The aim of the present study was to analyze by interphase fluorescence in situ hybridization (FISH) the incidence of numerical abnormalities for chromosomes 1, 9, 10, 11, 14, 15, 17, 22, X, and Y in a group of 70 consecutive meningioma tumors. Another goal was to establish the potential associations among the altered chromosomes, as a way to assess both intertumoral and intratumoral heterogeneity. METHODS: For the purpose of the study, 70 patients diagnosed with meningioma were analyzed. Interphase FISH for the detection of numerical abnormalities for chromosomes 1, 9, 10, 11, 14, 15, 17, 22, X, and Y was applied to fresh tumor samples from each of the patients studied. RESULTS: The overall incidence of numerical abnormalities was 76%. Chromosome Y in males and chromosome 22 in the whole series were the most common abnormalities (46% and 61%, respectively). Despite the finding that monosomy of chromosome 22/22q(-) deletions are the most frequent individual abnormality (53%), we have observed that chromosome gains are significantly more common than chromosome losses (60% versus 40%). Chromosome gains corresponded to abnormalities of chromosomes 1 (27%), 9 (25%), 10 (23%), 11 (22%), 14 (33%), 15 (22%), 17 (23%), and X in females (35%) and males (23%) whereas chromosome losses apart from chromosome 22 frequently involved chromosomes 14 (19%), X in males (23%), and Y in males (32%). Although an association was found among most gained chromosomes on one side and chromosome losses on the other side, different association patterns were observed. Furthermore, in the latter group, monosomy 22/22q(-) was associated with monosomy X in females and monosomy 14/14q(-) was associated with nulisomy Y in males. In addition, chromosome losses usually involved a large proportion of the tumor cells whereas chromosome gains were restricted to small tumor cell clones, including tetraploid cells. CONCLUSIONS: Our results show that meningiomas are genetically heterogeneous tumors that display different patterns of numerical chromosome changes, as assessed by interphase FISH.     

Fine needle capillary sampling of eyelid masses. A study of 70 cases

OBJECTIVE: To study the cytomorphology of eyelid tumors, correlate it with histopathology and determine the diagnostic accuracy of fine needle capillary (FNC) sampling (nonaspiration) in the evaluation of lid tumors. STUDY DESIGN: A prospective study of 70 cases of eyelid masses carried out using FNC, with confirmation by histology in 66 cases and peripheral blood smear and bone marrow examination in 3. Histology was not done in 1 case, and 11 cases were inadequate on cytology. The diagnostic accuracy of cytology was 94.73%, and false negativity was 5.17%. RESULTS: The ages of the patients ranged from 3 to 75 years, with a mean of 40.4. The male/female ratio was nearly equal (37:33). The upper eyelid was affected in 45 cases and lower lid in 25 cases. The right eye was affected in 35 cases, left eye in 34 cases and both eyes in 1 case. Fifteen benign, 35 malignant and 9 infectious/inflammatory lesions were encountered, with 11 inadequate smears. CONCLUSION: FNC sampling is an effective method of sampling eyelid tumors because it causes little discomfort to the patient and allows the operator to maintain better control over the procedure. A distinction between inflammatory, benign and malignant lesions and between the types of malignant tumors can be made.     

Iris pigmentation as a quantitative trait: variation in populations of European,East Asian and South Asian ancestry and association with candidate gene polymorphisms

In this study, we present a new quantitative method to measure iris colour based on high‐resolution photographs. We applied this method to analyse iris colour variation in a sample of individuals of East Asian, European and South Asian ancestry. We show that measuring iris colour using the coordinates of the CIELAB colour space uncovers a significant amount of variation that is not captured using conventional categorical classifications, such as ‘brown’, ‘blue’ or ‘green’. We tested the association of a selected panel of polymorphisms with iris colour in each population group. Six markers showed significant associations with iris colour in the European sample, three in the South Asian sample and two in the East Asian sample. We also observed that the marker HERC2 rs12913832, which is the main determinant of ‘blue’ versus ‘brown’ iris colour in European populations, is also significantly associated with central heterochromia in the European sample.     

Fluoroangiography of various pathological pictures in unusual observations of the anterior segment

Fluorangiography is a very important investigation in order to have a differential diagnosis in all pathological pattern of the conjunctiva of scleral corneal limbus of the sclera of the iris of the ciliary-body. We have in the literature two different patterns: A) Fluorescein negative pattern (cystic neoformations, benign tumors with or without pigment) B) Fluorescein positive pattern (inflammatory pseudotumors, malignant tumors). Authors agree more or less with this classification; they have, moreover, worked out some variations. In our case of a localised carcinoma, fluorescein positive, we did not observe less of fluorescein; in the iris melanoma, even this fluorescein positive, in all observed cases has shown only a small loss of fluorescein near his edges. In the other cases as in the leiomyoma and cystis we agree with the literature even with prudence.     

5774例临床生育不良者异常染色体核型分析及32种人类染色体新核型报告

为了探讨异常染色体核型在临床生育不良人群中的分布及其与临床生育结局的关系, 采用常规方法制备外周血淋巴细胞染色体, 经G显带, 对 5 774例临床生育不良者做了外周血染色体核型分析, 检查出异常核型550 例。其中三体核型 255 例占 46.36％, 相互易位 91 例占 16.55％, 染色体倒位 85 例占 15.45％, 染色体缺失 81 例占 14.73％, 罗伯逊易位21例占3.82%, 短臂增加7例占1.27%, 大丫6例占1.09%, 随体异常4例占0.73%。其中 32 例为首次报道的新核型。其临床结局有流产、不育、先天畸形等。结果表明携带异常核型染色体, 可能是影响生育的重要原因之一。     

A case of Allgrove (Triple A) syndrome associated with renal ectopia

Allgrove syndrome (triple-A syndrome) is an autosomal recessive disorder characterized by adrenocorticotropin hormone-resistant adrenal insufficiency, achalasia and alacrima. Aside from the classic features of the syndrome, several abnormalities including mainly neurological abnormalities have been reported in the syndrome. Herein, we presented a case of Allgrove syndrome associated with left renal ectopla. To the best of our knowledge renal abnormality in Allgrove syndrome has not been reported in the literature until now. We think that ectopic kidney diagnosed in our patient is coincidental because the incidence of renal ectopia is high, approximately 1 in 900 in population.