History Of Consanguineous Marriage Research Articles

Primary IgA and IgG subclass deficiency in a 17-year-old Pakistani girl: a case report

Primary immunodeficiency disorders pose a diagnostic dilemma for physicians in the developing countries such as Pakistan because of lack of adequate diagnostic facilities. We present here the case of a 17-year-old girl who had a history of recurrent respiratory tract infections since childhood and had been treated with anti-tuberculous medications thrice; for a total of 24 months. She had also received multiple courses of antibiotics. Her initial presentation to our hospital was with acute bronchopneumonia. Her past medical history of recurrent infections also alerted the treating physician to the possibility of bronchiectasis secondary to a variety of underlying potential pathologies such as post-infection, immunodeficiency syndromes or ciliary dyskinesia disorders. Cystic fibrosis was also an important consideration. Direct enquiry revealed that there was no history of consanguineous marriage in her parents. Her sweat chloride test was within normal range (<40 mmol/L). Blood analysis was performed which showed IgA, IgG2 and IgG4 deficiency. She has been following up at our hospital for the past few years. In that course of time, she has had multiple episodes of pneumonia, gastroenteritis and maxillary sinusitis. She was successfully treated with intravenous immunoglobulins on four occasions when she presented with systemic crisis secondary to severe systemic infection. She also developed biopsy proven intermediate grade non-Hodgkin’s lymphoma five years after the diagnosis of immunoglobulin deficiency was first made. This appeared to be a complication of her immunodeficient state. She has been receiving chemotherapy for the lymphoma. Physicians should be cognizant of the morbidity that primary immunodeficiency syndromes such as immunoglobulin deficiency can have in the form of multiple infections and increased risk of malignancies as seen in our patient.

Childhood convulsion and hemiparesis due to schizencephaly-a case report

Childhood convulsion with hemiparesis due to schizencephaly is a rare condition. It is a developmental disorder of neuronal migration, characterized by early focal destruction of the germinal matrix and surrounding brain before the cerebral hemispheres are fully formed at 1-5 months of gestation .The lesion is most likely related to multiple aetiologies including genetic, toxic, metabolic, vascular or infectious agents. This case is reported due to its worldwide rarity. INTRODUCTION Schizencephaly, a developmental disorder of neuronal migration is characterized by cleft in cerebral mantle, which communicates between the subarachnoid space laterally and ventricular system medially. This disorder was originally described by Wadsworth and Yakolev. 1 Their original work describes schizencephaly to result from failure of normal migration of primitive normoblasts resulting in cerebral cleft .The cardinal neuropathological features are і) Hemispheric cleft іі) communication of subarachnoid space with lateral ventricle medially ііі) Infolding of grey matter along the cleft iv) Multiple associated intracranial malformations including polymicrigyria, absent septum pellucidum, optic nerve hypoplasia. The presentation and outcome are variable i.e. hemiparesis, developmental delay, microcephaly, mental retardation and most patients have seizures. CASE REPORT A 2 year aged female child was admitted in paediatric neurosurgery ward of CM Hospital Dhaka with complain of repeated episode of convulsion since birth and weakness in right upper and lower limbs since two months of age. She was symptomatically treated with anticonvulsant sodium valproate. The child was delivered full term normally at home with unremarkable antenatal maternal history. She cried soon after birth and there were no postnatal complications. There is no history of consanguineous marriage. On physical examination child had normocephaly, no dysmorphism of face. Anterior fontanelle was normal. Sutures were widely normal. There was a global delay in the developmental milestones. Muscle tone of the right upper and lower limbs showed spasticity with 4/5 power grade with normal reflexes. Vitals were normal. Anthropometric measurements of weight and length were within normal limits. The child was admitted with provisional diagnosis of Cerebral palsy. Investigations done revealed normal Hb, Tc, Dc. EEG showed abnormal record with seizure pattern. CT scan showedSCHIZENCEPHALY. Figure 1 Fig: CT scan of brain to show schizenencephaly Thus the diagnosis was established with the help of CT scan report. The option of treatment with prognosis was explained to the parents. She eventually underwent cystoperitonreal shunt. Postoperative recovery was uneventful except an episode of seizure that was managed by sodium valproate. Childhood convulsion and hemiparesis due to schizencephaly-a case report 2 of 3 Counseling was given and physiotherapy was advised. Anticonvulsant was continued. DISCUSSION Schizencephaly is a rare developmental disorder of neuronal migration. It is characterized by CSF filled cleft, lined by grey matter and extends across the entire cerebral hemisphere from ependyma to the periphery of the brain 12. Types of Schizencephaly: Type I: Closed type (lips of cleft are fused) Type II: Open type (clefts are separated) Type II is more common than type I

The prevalence of patients with ocular genetic disorders attending a general paediatric ophthalmology clinic in the East End of London

To document the prevalence of ocular genetic disorders in a general paediatric ophthalmology clinic in a deprived, ethnically diverse inner city area of London, and to assess the consanguineous relationships and ethnicity among families with these conditions. A prospective audit documented all ocular genetic conditions (excluding strabismus and amblyopia) presenting for 16 consecutive weeks to the paediatric ophthalmology clinic. Information regarding ethnicity and consanguinity were sought. The disorders were divided according to the mode of inheritance if known. Thirteen per cent of patients (45/342) had an ocular genetic disorder or were being examined for one. Of them, 22% (10/45) had a history of consanguinity with an inheritance pattern of 30% autosomal recessive (3/10), 20% autosomal dominant, 50% X-linked/unknown/isolated cases. In the remaining non-consanguineous families (35/45), 22% were autosomal recessive, 17% autosomal dominant, and 60% X-linked/unknown/isolated cases. The vast majority of cases (9/10) with a history of consanguineous marriage had South Asian ancestry. Variable ethnic backgrounds were documented for patients with genetic disease and no consanguinity. Ocular genetic disorders are common in secondary care. Less than a third of patients with such disorders had a family history of consanguinity. The proportion of patients with proven autosomal recessive disease was similar irrespective of consanguinity within family. The proportion of children of South Asian ancestry was high in this clinic population.

Binocular membranous cataract associated with binocular retinal detachment

A 36-year-old man with a history of consanguineous marriage between his parents presented with bilateral membranous cataract that was complicated by bilateral rhegmatogenous retinal detachment (RRD). Biomicroscopy revealed an absence of the crystalline lens bilaterally, a single piece of integrated fibrotic membrane in the right eye, and a membrane with a central cleft at the level of the ciliary process in the left eye. A small amount of residual cortex was revealed in the peripheral part of the membranes bilaterally when the pupils were dilated. Funduscopic examination showed that the vitreous liquefied and retina detached bilaterally. The successful retinal reattachment by vitrectomy and the finding of a retinal tear proved that the RD was rhegmatogenous. This case investigates bilateral membranous cataract with bilateral RRD as a new syndrome, or whether RRD may be a new complication of membrane cataract.

Risk factors for breast cancer for women in Punjab, Pakistan:Results from a case-control study

Over the last three decades an increase in the incidence of breast cancer has been observed in the previously low-risk Asian countries. This study is designed to determine the risk factors of breast cancer for Pakistani women as little information exists in this regard. A case-control study of 564 female breast cancer cases diagnosed at the two cancer hospitals at Lahore (INMOL and SKMCH) during the time period Jan 1, 1998 to Dec 31, 1998 was carried out. Four hundred and forty eight women aged 24-80 years out of 564 cases were complete with respect to defined criteria and were eligible for the study. Population-based controls were selected to match for age of cases in the ratio 1:2. The data were analyzed considering ‘all women’ and then separate analyses were done for ‘premenopausal’ and ‘postmenopausal women’. Women with family history of breast cancer, history of consanguineous marriage, smoking and high BMI (≥28) are at increased risk of breast cancer for all three groups. Early menarche (45 years) was a strong determinant of breast cancer. Higher number of full-term pregnancies (>3) was protective for ‘all women’ and ‘premenopausal women’ but in case of ‘postmenopausal women’ the poor with higher number of pregnancies were significantly protected. Late age at first FTP (>25 years) is a significant risk factor for postmenopausal women.

Cardio-Facio-Cutaneous Syndrome: Two Cases in the Same Generation

A 4-year-old Japanese boy, the youngest of three brothers, presented with ichthyosiform hyperkeratosis over his whole body, eczematous erythema with partial desquamation and erosion on the flexor side of the joints of extremities, the fossa axillaries, and the genital and buttock regions, and total hair loss on the scalp and the absence of eyebrows and eyelashes. In addition to the ichthyotic eruptions and hair abnormalities, he also had a ventricular septal defect, mental retardation, growth retardation, characteristic facial features such as a depressed nasal bridge, low-set ears, and ocular hypertelorism; therefore, he was diagnosed with cardio-facio-cutaneous (CFC) syndrome. The patient's family did not have a history of consanguineous marriage. The parents and the eldest son were healthy. However, the second son, also born with ichthyosiform hyperkeratosis over his whole body, total hair loss on the scalp, myocardial deficiency, mental retardation, growth retardation, and characteristic facial features, had died of pneumonia and sepsis at the age of 1.5 years. Because the middle brother had the same disease, the present case is considered to be a rare case of CFC syndrome with in a single generation.

A founder mutation in the CLCNKB gene causes Bartter syndrome type III in Spain

The term "Bartter syndrome" encompasses a group of closely related inherited tubulopathies characterized by markedly reduced NaCl transport by the distal nephron. At present, five different genetic variants have been demonstrated. The majority of patients with so-called classic Bartter syndrome carry inactivating mutations of the CLCNKB gene encoding the basolateral ClC-Kb chloride channel (Bartter syndrome type III). The purpose of this study was to investigate the underlying mutation in cases of classic Bartter syndrome followed at our center. Ten patients, including two sisters, with clinical and biochemical features of classic Bartter syndrome were included in the mutational analysis. They originated from different regions of Spain with either Basque or Spanish ancestry. There was no history of consanguineous marriage in any of the kindreds. The parents and siblings of each patient, as well as a population of 300 healthy control adult subjects, were also analyzed. All ten patients were found to be homozygous for an identical missense mutation in the CLCNKB gene, substituting a threonine for an alanine at codon 204 (A204T) in the putative fifth transmembrane domain of the protein. None of the 300 control subjects were homozygous for the A204T allele. Overall, the A204T mutation was detected on 2/600 control chromosomes. Despite sharing a common mutation, the clinical manifestations of the syndrome in the patients varied from lack of symptoms to severe growth retardation. Demonstration of a point mutation within the CLCNKB gene as the apparently unique cause of Bartter syndrome type III in Spain is highly suggestive of a founder effect. Our results also support the lack of correlation between genotype and phenotype in this disease.

HLA DR phenotypic frequencies and genetic risk of Type 1 diabetes in west region of Algeria, Tlemcen

BackgroundThe main genomic region controlling the predisposition to type 1 diabetes is the Human Leukocyte Antigens (HLA) class II of the major histocompatibility complex. Association with different HLA types depends also on the studied populations. In our investigation, we tried to measure the phenotypic HLA class II association frequencies of DR3 and/or DR4 antigens, using a serologic method called microlymphocytotoxicity analysis, in diabetic and nondiabetic (ND) subjects originating from the west-Algerian region of Tlemcen. The aim of the present study was to determine which HLA DR antigens represent a high susceptibility to develop the disease in this area. Using a case-control retrospective study design, we randomly recruited ninety-one related subjects, 39 type 1 diabetics and 52 ND as controls, at the Internal Medicine Board of Medical Centre University of Tlemcen.ResultsDR3 antigen frequencies were comparable between the type 1 diabetics and the ND subjects and showed no association with the disease (p = 1.000, OR = 0.95), whereas DR4 and DR3DR4 antigens were associated with susceptibility to develop type 1 diabetes (DR4; OR = 2.10, DR3DR4; OR = 1.30). Also, no incidence for DR3 (p = 0.2646) or DR3DR4 (p = 0.0699) antigen frequencies was related to the sex ratio. However, significant differences in HLA DR4 frequencies between type 1 diabetics and ND were found to be related to sex (p = 0.0085).ConclusionTaken together, our investigation showed that the strongest association with type 1 diabetes was noticed in the presence of HLA DR4 antigens followed by DR3DR4 antigens. This study highlighted a characteristic of Tlemcen population; a history of consanguineous marriages. Association studies between the disease and genetic polymorphisms should be undertaken in a population where consanguinity is more limited to reduce confounding in result interpretations.

Familial recurrent molar pregnancy: a case report

Familial recurrent molar pregnancy: a case report

Primary Hemophagocytic Lymphohistiocytosis in Turkish Children

Nineteen children with hemophagocytic lymphohistiocytosis (HLH) were studied in the Department of Pediatric Hematology, Hacettepe University. Patients were divided into two groups. Group 1 : Thirteen patients were classified as having a genetic etiology (7 familial, 6 presumed familial) on the basis of an affected sibling and consanguinity. There was a history of consanguineous marriage in 13 of the families. Seven of them had a history of a sibling with HLH. Group 2 : Six patients were diagnosed with sporadic HLH. The age at presentation for familial patients was 0.7-84 months (mean 21.9 &#45 24.9 months), and for sporadic cases it was 2.5-48 months (mean 22.7 &#45 19.8 months). The clinical and laboratory data of these two groups were similar at diagnosis. Thirteen cases were diagnosed premortem by bone marrow aspiration. Splenic biopsy was performed in 2 patients. Four patients were diagnosed by postmortem examination. Elevated LDH levels were found in all patients tested. No significant differences for clinical and laboratory data were found between the two groups.

Primary Hemophagocytic Lymphohistiocytosis in Turkish Children

Nineteen children with hemophagocytic lymphohistiocytosis (HLH) were studied in the Department of Pediatric Hematology, Hacettepe University. Patients were divided into two groups. Group 1 : Thirteen patients were classified as having a genetic etiology (7 familial, 6 presumed familial) on the basis of an affected sibling and consanguinity. There was a history of consanguineous marriage in 13 of the families. Seven of them had a history of a sibling with HLH. Group 2 : Six patients were diagnosed with sporadic HLH. The age at presentation for familial patients was 0.7-84 months (mean 21.9 - 24.9 months), and for sporadic cases it was 2.5-48 months (mean 22.7 - 19.8 months). The clinical and laboratory data of these two groups were similar at diagnosis. Thirteen cases were diagnosed premortem by bone marrow aspiration. Splenic biopsy was performed in 2 patients. Four patients were diagnosed by postmortem examination. Elevated LDH levels were found in all patients tested. No significant differences for clinical and laboratory data were found between the two groups.

Consanguineous marriage in PR China: a study in rural Man (Manchu) communities

Although there is a long history of consanguineous marriage in China, information on its prevalence is very limited. The Man (Qing) dynasty ruled China for over 250 years, but no consanguinity studies have been reported on this important population. The objective of the present investigation was to determine the present-day level of consanguineous marriage in the Man community, and to compare the data with existing consanguinity information on other Chinese populations. The study was conducted in a group of 11 rural Man communities in the north-eastern Chinese province of Liaoning. Household-based interviews were conducted by local staff on 513 couples, 418 of whom were Man with another 95 Man-Han inter-ethnic marriages. Basic pedigrees were constructed to determine the biological relationship between each set of spouses. Thirty of the 418 couples were in a consanguineous union, with a mean coefficient of inbreeding f = 0.0012. The small population sizes of the study may have contributed to the spatial variation in the patterns of inbreeding. Across generations there was a reduction in consanguineous marriages and an increase in inter-ethnic unions, which paralleled changes in civil marriage regulations.

Xeroderma Pigmentosum.

Five cases of xeroderma pigmentosum have been presented, three of the patients belonging to one family. There was no history of consanguineous marriages in this series. All five patients had advanced ocular complications. Three presented with multiple basal cell carcinomata, which were treated by radiotherapy in two cases and surgery in one. One patient presented with a dermatofibroma, which does not seem to have been reported earlier in association with this disease. Reconstructive techniques such as the use of flaps and grafts arc safe, and the healing response is quite satisfactory.

Conjoined Twins: A Report of 3 Cases to Emphasize Prenatal Diagnosis and Challenges

Meeting challenges regarding conjoined twinning and its Prenatal Diagnosis is depicted by three pairs of conjoint twins (all female) diagnosed by ultrasound. All the pairs belonged to Hindu family and there was no history of consanguineous marriage, previous twins in family, ingestion of drugs or exposure to X-ray. First pair of thoracopagus twins was diagnosed at 28 weeks gestation born to twenty two years old primigravida. Second pair of twin was Cephalo-thoracopagus born to twenty seven years old second gravida with a history of one incomplete abortion (two years back). Third pair of twin was craniopagus thoraco-ompalopagus born to twenty five years old second-gravida and parity one at fifteen weeks of gestation. Incidences of female conjoint twins are more common. Management of conjoint twin still remains a challenge to modern sciences due to multiple congenital anomalies although early and easy diagnosis of conjoint twin is possible because of the availability of ultrasonography. Keywords: Conjoined twins, prenatal diagnosis and challenges DOI: http://dx.doi.org/10.3126/njog.v6i1.5255 NJOG 2011; 6(1): 57-60