Ellis van Creveld syndrome: An unusual presentation at birth

Ellis Van Creveld, a syndrome comprising of chondrodysplasia, bilateral polydactyly of the hands with skeletal abnormalities, and congenital heart defect is a rare autosomal recessive disease. The prevalence of the disease in the world is 1/6000–20,000 newborns. In the Indian population, it is difficult to estimate the exact prevalence of the disease but, it is mostly seen in the Amish population. The cardinal features are short stature, dysplastic nails and teeth, polydactyly, narrow chest, and heart defects. The crucial differentials are Jeune dystrophy, Weyers syndrome, and McKusick-Kaufman syndrome. Here, we report a neonate, born of a non-consanguineous marriage with a syndromic appearance consisting of a bell-shaped chest, polydactyly, natal teeth, and single atrium. Prognosis is related to respiratory and heart defects in the early neonatal period.

Iniencephaly

Iniencephaly is an uncommon form of neural tube defects which is characterized by retroflexion of the head and absence of neck as a consequence of defective closure of the vertebral body and arch. Multiple identified risk factors for its causation include environmental, genetic and drugs. We report a case of 38-year-old woman with prior history of still birth and abortions who presented at 35 weeks of gestation with lower abdominal pain and high blood pressure. Mother had consanguineous marriage. Her hypothyroidism was untreated in the first and second trimester. She delivered an iniencephalic baby girl via emergency c-section with multiple malformations at 38 weeks gestation secondary to fetal cardiac deceleration. Baby survived for less than 18 hours. In this case, proper antenatal care and follow up visits were needed along with postnatal genetic and pathological evaluation including assessment of risk factors. Appropriate management is important to prevent complications and recurrence in subsequent pregnancies.

Early infantile form of Krabbe disease: a case report

A 7-month-old female child, born to 2nd degree consanguineous marriage brought with complaints of gross developmental delay. Her examination revealed spasticity in all 4 limbs with brisk deep tendon reflexes with intact primitive reflexes and exaggerated startle reflex. Her MRI brain showed demyelination signs in bilateral thalami, dentate hila, and thickened optic chaisma. Age of presentation, clinico-radiological findings were suggestive of early infantile form of Krabbe disease.

Analysis of familial cases of primary immunodeficiency in the context of genetic counseling

Primary immunodeficiencies (PID) are caused by defects in genes of immune system. The mutations may occur de novo or can be inherited. The frequency of familial PID cases varies in different populations and depends on multiple factors. The aim of this study was to analyze familial PID cases among pediatric patients from NMRCPHOI D. Rogachev. The study was approved by the Independent Ethics Committee and the Scientific Council of the D. Rogachev NMRCPHOI. 1075 children from 1020 families with molecular PID diagnosis were analyzed retrospectively. One hundred and forty-six children had at least one relative with the same disorder; mutations were identified in 31 PID’s genes. The frequency of familial cases was 13.6%. The proportion of families with two or more affected children was 5.4%. Patients born in a consanguineous marriage made up 3% of the observed children. Autosomal dominant PID were typical for families with affected adult relatives. Because of the high amount of familial cases, all parents of children with PID as well as adult PID patients of childbearing age should seek a familial genetic counselling immediately after the corresponding diagnosis. Patients whose PID diagnosis has not been genetically verified, should be urgently tested to find an underlying molecular genetic cause of the disease. Prenatal/preimplantation diagnostic and screening of their close relatives are very important in these families.

The prevailing trend of consanguinity in the Arab society of Israel: is it still a challenge?

The aim of this study was to determine the trend of consanguineous marriage among the Arab population in Israel. Socio-demographic data for the Arab population were extracted from national health surveys conducted in Israel in 2007 and 2017. The prevalence of consanguineous marriage among the Arab population in Israel increased significantly from 36.3% to 41.6% in the decade from 2007 to 2017. First-cousin and closer marriages constituted about 50% of total consanguineous marriages in the two periods surveyed. Consanguinity was found to be significantly related to religion and place of residence. Thus, the prevalence of consanguineous marriage remains high among the Arab population in Israel, similar to other Arab societies. These findings affect the health of future generations and impose a challenge for health care professionals.

Is consanguineous marriage related to spousal violence in India? Evidence from the National Family Health Survey, 2015–16

Violence against women is a global phenomenon, and intimate partner violence is the most common form of violence faced by women in the world. Around 30% of women in the world, on average, and 33% in India experience intimate partner violence during their lifetime. The main aim of this study was to investigate whether consanguinity protects women from spousal violence. National Family Health Survey 2015–16 (NFHS-4) data were used. The study sample comprised 60,824 currently married women aged 15–49 years. The results of the logistic regression model showed that the likelihood of all types of spousal violence against women was higher among consanguineous unions compared with non-consanguineous unions in India. The association between consanguineous marriage and spousal violence was found to be positive and significant in the southern and eastern regions of India and among Scheduled Castes and Scheduled Tribes. The association was not significant among Muslims. Differences in socio-cultural norms and practices across the regions of India, and among different socio-cultural groups, can perhaps explain these variations. Women belonging in higher age groups, from Other Backward Castes, those who were working and those with a low level of educational attainment and socioeconomic standing had a higher risk of experiencing intimate partner violence. Couples in a consanguineous marriage should be given adequate counselling to reduce intimate partner violence in India, and similarly culturally diverse countries. This would also help reach Target 5.2 of the Sustainable Development Goals by 2030.

Parental consanguinity and congenital heart defects in Afghan children with Down’s syndrome

Background: It seems that parents’ consanguinity status effects the pattern of congenital heart defects (CHDs). In this study the CHD pattern in children with Down’s syndrome (DS) was determined in Afghanistan’s children population with a high consanguineous marriage rate and compared with historical cohorts from populations with low prevalence of parental consanguinity. Objective: This analytic cross sectional study aimed to determine the frequency and distribution of CHDs in Afghanistan children with Down’s Syndrome as a group in a community with a high consanguineous marriage rate and comparing these with different global studies and populations with low prevalence of consanguinity. Methods: This analytic cross sectional study was conducted in a pediatric teaching hospital in Kabul city - Afghanistan, named Maiwand Hospital. The subjects were all children with DS proven by clinical and cytogenetic study and referred to the pediatric cardiology service from September 2018–September 2020. Parents’ consanguinity was documented and 2D echocardiography and Doppler studies were performed by two experienced pediatric cardiologists after physical examination, ECG, and chest X-ray for each patient. Results: During the two-year study period, 120 DS patients were identified, 78 (65%) of whom had CHDs. The prevalence of isolated and multiple CHD in the 78 children with DS were 35% (42 patients) and 30% (36 patients), respectively. Ventricular septal defect (20.5%) and atrial septal defect (15.3%) were the most common isolated defects. The combination of VSD and PDA (20.5%) were the most frequent multiple CHDs. The most com­mon associations of CHD were VSD + PDA (20.5%) and VSD + ASD (10.2%). Consanguinity was found in 69.2 % of all parents. Conclusions: A higher frequency of CHD was documented in DS children from this population with a high consanguineous marriage rate. The frequencies of specific lesions were almost similar to those reported locally and internationally; VSD was the most frequently detected in this study. Interesting was the predominance of left-right shunt lesions and the relative rarity of cyanotic and complex CHD in this DS population. key words: congenital heart disease, atrioventricular septal defect, Down’s syndrome, trisomy 21, Afghanistan

P094 “Neonatal lupus”: a unique name for very different realities

Background Neonatal lupus is a rare condition linked to the maternal-fetal transmission of maternal anti-SSA and/or anti-SSB antibodies, more rarely anti-U1-RNP. The most frequent clinical manifestations are cardiac and cutaneous, more rarely hematological (thrombocytopenia, leuco-neutropenia), hepatic (cholestasis), neurological (spastic paresis, lymphocytic meningitis) or renal. We report two observations of neonatal lupus: a classic form, and a rare form. Observations First case: A female newborn, premature of 37 weeks, from a first-degree consanguineous marriage, having a mother followed for systemic lupus erythematosus, with poor therapeutic compliance, presented at H1 of life with neonatal respiratory distress. The clinical examination revealed severe bradycardia at 67 Bpm. The electrocardiogram showed complete atrioventricular block, with a moderate pericarditis on the echocardiography, minimal tricuspid insufficiency, interatrial communication, and a 6 mm foramen oval with LR shunt. The immunological test had objectified positive antinuclear, anti-SSA and anti-SSB antibodies. An implementation of a pacemaker with inter-atrial communication ligation were performed successfully. The evolution was marked by the appearance of a malar erythema with generalized lesions of discoid lupus at the age of 14 months, treated with local corticosteroid therapy, with good outcomes. The control immunological workup was negative at 18 months. Second case: A 2-month-old boy from a non-consanguineous marriage with a mother followed for Sjögren's syndrome was admitted for a symptomatology dating back to birth marked by the appearance of diffuse petechial purpura. Clinically, the infant presented diffuse discoid macules throughout the body. The somatic examination, particularly cardiovascular, was normal. The biological workup showed haemolytic anaemia with a positive coombs test and severe thrombocytopenia. The electrocardiogram and echocardiography were normal. The immunological workup had objectified positive anti-SSA, anti-SSB and anti-nuclear antibodies. The infant was treated by oral corticosteroids (prednisolone) for 4 months, with good outcomes. The control immunological workup was negative at 6 months. Conclusion The clinical manifestations of neonatal lupus are polymorphic, and the only one that may expose to life threat is complete atrioventricular block. All mothers with known lupus or with positive anti-SSA autoantibodies should be monitored during pregnancy with repeated ultrasounds.

FIRST REPORTED CASE OF MAJEED SYNDROME FROM PAKISTAN

Majeed syndrome, characterized by chronic recurrent multifocal osteomyelitis and congenital dyserythropoeitic anemia, is a rare disease reported in children. We report a case of Majeed Syndrome in a 9-year-old boy, born of consanguineous marriage reporting to us for treatment of anemia, requiring blood transfusion. He underwent below-knee-amputation due to unresolving recurrent osteomyelitis at multiple sites. There was history of pain insensitivity and fever during hot weather as well. His interleukin-6 levels were raised. This is the first case of Majeed Syndrome from Pakistan and first in the world with Hereditary Sensory Autonomic Neuropathy type 4 as an associated feature.

Consanguineous Marriages in India: Prevalence and Determinants

Consanguineous marriage is the legal union of male and female of a common ancestor related by blood. The most common prevailing form of consanguineous marriages is between first cousins. Middle East Asian countries and southern states in India show high prevalence. A comparative analysis between the two rounds of National Family Health Survey 1 and 4 have shown a declining trend for the practice of consanguineous marriages. The highest percentage of consanguineous marriages is seen among the first cousins from both father’s and mother’s side, most commonly practice in the southern states of Andhra Pradesh, Telangana, Tamil Nadu, and Karnataka except Kerala. Importantly, the practice of consanguineous marriage is higher among the Muslims of North India and Hindus of Southern India, among the Other Backward Classes and the less educated population of the middle and richer wealth index. A significant relationship can be noticed among consanguineous marriages and socio-economic variables.