Frontonasal Malformation Diagnosis in the First Trimester: A Case Report Abstract Different components of the face and the brain develop independently and ultimately unite at the midline. Disruptions in the development and fusion of craniofacial midline give rise to myriad of abnormalities broadly classified as frontonasal malformations. Here, we report a case diagnosed in the first trimester. The fetus had midline cleft of the face extending till forehead, cleft lip and palate, absent nasal tip and arhinia. There was associated alobar holoprosencephaly and polydactyly in all the four limbs. This case illustrates the importance of evaluation of facial profile, retronasal triangle and 3 D scanning at the time of first trimester screening.

Antenatal Diagnosis of Bilateral Proximal Femoral Focal Deficiency (PFFD) Abstract Proximal femoral focal deficiency (PFFD) is a rare skeletal dysplasia, characterized by hypoplasia of the subtrochanteric femur with variable degrees of shortening of the femoral shaft. There are numerous gene e.g. TBX4, FGF, FGFR, TP63 and HOX responsible for limb formation, type and its shape. Normal limb development is three dimensional; proximodistal axis regulated by AER; anteroposterior axis (preaxial/postaxial) governed by SHH with ZPA and dorsoventral axis controlled by LMX1B. Primigravida with diamniotic dichorionic twins in first trimester was found to have absent right femur, fibula and left femural bone with hypoplastic right foot in one foetus. Right tibia, both left tibia and fibula and left foot were visualized normally. Bilateral humerus, radius and ulna along with digits were visualized with no evidence of oligodactyly. Twin II had no major limb reduction defect. Both nasal bones, hard palate were visualized; nuchal translucency was within normal range for the foetus of 13 weeks 3 days of duration; suggestive of bilateral PFFD; Aitken type 4 in Twin I. We are the first to describe bilateral PFFD in the first trimester of pregnancy. Nuchal scan provides a window of opportunity to the foetal medicine specialists to screen the foetus for major congenital anomalies and to proceed with further investigation or with selective reduction as in this case so as to optimize the pregnancy outcome. Identification of PFFD at 13 weeks with foetal reduction helped in minimizing the risk to the surviving foetus.

Umbilical Cord Abnormalities and Pregnancy Outcome Abstract Umbilical cord anomalies can be related to its morphology (coiling, length and thickness); placental insertion (marginal and velamentous insertion); in utero distortion (knotting, torsion and nuchal cord) vascular abnormalities (single umbilical artery) and primary tumours or masses (haemangioma and teratoma). Some of these conditions may be associated with other foetal abnormalities or aneuploidy. On the other hand, several prenatal complications including intrauterine growth restriction IUGR and stillbirth can be attributed to cord accidents or abnormalities. Early detection and close follow up of umbilical cord abnormalities can reduce the risk of morbidity and mortality and assist in decision making. To understand the normal development of the umbilical cord and discuss several pathologic processes which are involved in different cord abnormalities.

Exome Sequencing Identifies RET Associated Hirschsprung Disease in a Fetus with Echogenic Bowel Abstract This is report of a case of RET associated Hirschsprung disease in a fetus diagnosed using exome sequencing. The fetus initially presented with echogenic bowel at 16 weeks with maternal first trimester serum screen showing increased risk for Trisomy 21. Amniotic fluid karyotype, ΔF508 CFTR genotype and maternal TORCH serology were normal. Subsequent ultrasonograms showed dilated bowel loops, predominantly large bowel. Following delivery at 24 weeks, a post-mortem examination was performed. Dilated bowel was confirmed with no structural gut abnormality and no other dysmorphic finding. Histopathology revealed agangliosis confirming a diagnosis of Hirschsprung disease. Exome sequencing done on fetal DNA from amniotic fluid revealed a putative pathogenic heterozygous c.1438G > A variant in exon 7 of RET gene, which was inherited from the asymptomatic mother. This enabled genetic counseling and prenatal diagnosis in subsequent pregnancy.

Women with Positive First Trimester Thyroid Disease Screening Results Abstract The objective of this study was to follow up women with positive results on routine antenatal screening for maternal thyroid disease. Between November 2009 and September 2015, women having a first trimester Down’s syndrome screening test were simultaneously screened for thyroid disease; those symptomatic or being investigated for thyroid problems were excluded. A blood sample was tested for anti-thyroid peroxidase antibodies and serum thyroid stimulating hormone, and in the first half of the study also for free thyroxine. Women with at least one analyte outside the range were classified as positive and referred to an endocrinologist for counselling. Among 10,052 women that were screened, 1190 (11.8%) were positive. Follow-up information was sought and this was available on 818 referrals. No further action was recommended in 440 (54%) and after repeat testing in 108 (13%) a total of 204 (25%) were recommended to take thyroxine, one was referred for surgery and propylthiouracil was recommended for five. Screening in the Czech Republic identifies an estimated 3.1% of pregnant women with subclinical thyroid disease.

Cystic Lesion in the Fetal Scalp: A Systematic Approach Abstract During an anomaly scan, cystic lesion in the scalp may be encountered while examining the fetal head. Some of these originate from the scalp tissue and can be dealt with postnatally by simple excision. Others may be more than just scalp cysts and have an intracranial communication. The objective of this communication is to illustrate a few cystic lesions in the fetal scalp and suggest a systematic approach in arriving at a diagnosis.

Prenatal Diagnosis of Atretic Occipital Cephalocele: A Case Report Abstract Atretic cephaloceles refer to the congenital herniation of meningeal and vestigial tissues such as arachnoid, glial or neural rests. These small, skin covered subscalp lesions usually appear within a few centimetres of the lambda and nearly half of them have a parietal situation, the remaining half have occipital, parieto-occipital, frontal, asterion, and sincipital locations. Atretic cephaloceles can be isolated or associated with congenital syndromes, agenesis of corpus callosum, grey matter heterotopias, ventriculomegaly, mental retardation, developmental delay, epilepsy, spasticity, speech difficulty, strabismus, optic nerve atrophy, microphthalmia, enophthalmos, cleft palate, hypertelorism, congenital cardiac and vascular defects, renal agenesis, hearing problems, congenital lobar emphysema, and muscular anomalies. This case report describes a newborn which has been diagnosed with atretic occipital cephalocele prenatally and also bilateral cochlear hypoplasia postnatally.

Gaucher Disease in Fetus: The Usual and the Unusual Presentations in a Family Abstract Gaucher disease is the most common of the lysosomal storage disorders, with a continuum of clinical features ranging from a perinatal lethal form to an asymptomatic form. Perinatal lethal Gaucher disease (PLGD), also known as fetal Gaucher disease is a distinct, severe form of type II Gaucher disease and typically presents as non- immune hydrops fetalis, hepatosplenomegaly and ichthyosiform abnormalities in the fetal life. We herein report a family with a spectrum of usual (i.e. hepatosplenomegaly) and unusual (i.e. absence of hydrops and presence of significant intrauterine growth restriction) features of PLGD with a genetic diagnosis of homozygous RecNciI mutation in the GBA gene.

Focus on Prenatal Detection of Micrognathia Abstract Fetal micrognathia involves abnormal or arrested development of the fetal mandible. Till recently, the prenatal diagnosis was subjective, based on the evaluation of the fetal profile and assessment of the relationship between the maxilla and the mandible. Recently objective sonographic methods have been utilized for diagnosing micrognathia such as the inferior facial angle, the jaw index, the frontal nasomental angle, the mandible width/maxilla width ratio and the mandibular length. Another useful sonographic sign, the mandibular gap in the retronasal triangle view, increases the accuracy of the diagnosis early in the first trimester. 3D sonographic views can add to the diagnosis and prenatal MRI is a useful adjunct to ultrasound in cases of limited acoustic window, maternal obesity, oligohydramnios and anterior spine position. The identification of micrognathia should prompt karyotyping and sonographic investigation for other abnormalities. The outcome of fetuses with this seemingly isolated finding is more guarded than one would intuitively believe, and the parents should be counseled accordingly. Postnatal complications including mild to severe upper airway obstruction leading to respiratory distress, feeding difficulties and mild to severe long-term developmental delay are common. One should be careful in pronouncing a fetus having ‘micrognathia’, especially on subjective evaluation, as this term implies that the fetus is abnormal with presence of significant pathology. There is no ‘gold standard’ for a definitive diagnosis of micrognathia on post-natal evaluation. Using a combination of objective sonographic markers as well as follow-up ultrasound assessments can significantly reduce the risk of a false diagnosis. Follow-up scans should be arranged, and neonatal service should be alerted in cases of ongoing pregnancies.

Role of TUI in First Trimester Evaluation of Palate Abstract The purpose of the study is to report on the application of tomographic ultrasound imaging (TUI) in prenatal sonographic study of fetal palate in 11–14 week scan. TUI is a technology that allows the examiner to obtain a volume data set that allows the display of numerous 2D slices from a given volume on any of the three orthogonal planes. It allows automatic slicing of the volume datasets displaying multiple parallel images. The fetal palate was examined with TUI in thirteen abnormal volumes and in ninety-four normal volumes. The appearance of maxillary line in sagittal sections and the base of the retronasal triangle in coronal sections serve as key landmarks in evaluating palatine clefts. The intact palatal line in sagittal sections was observed in all the ninety-four normal volumes. The midline anatomy of the palate has been described in the study emphasising that the vomer can mimic palate in midsagittal section in secondary palatine clefts. The parasagittal sections truly reflects the presence or absence of the palate without the confounding factor of the vomer bone which was demonstrated in the abnormal volumes with TUI. The potential advantage of TUI in evaluating palate is that it allows the display of both midsagittal and parasagittal sections simultaneously. The different types of cleft have a constant reproducible pattern in TUI imaging which can be used to diagnose palatine clefts including isolated cleft of palate. Prospective studies are needed to confirm these promising results.