Prenatal diagnosis and delivery of megalencephaly–capillary malformation syndrome

Background

Hemimegalencephaly (HME) is a rare neurological condition defined as a hamartomatous overgrowth of one cerebral hemisphere.1 There is currently no epidemiological data regarding its prevalence and incidence. The pathogenesis is believed to occur due to an increased number or size of neural cells; however, the exact mechanism can vary, depending on the underlying aetiology.2 HME can occur in isolation or be linked to genetic syndromes. When encountered prenatally, a multidisciplinary approach is optimal. Here we describe the course from prenatal diagnosis through delivery of a fetus with HME secondary to megalencephaly–capillary malformation syndrome.

Case presentation

A G2P1001 vaginally parous woman (patient in her late 20s) presented at 19 weeks of gestation for a routine ultrasound anatomical survey. She had no obstetric complications in her prior pregnancy. The fetus had asymmetric left lateral ventriculomegaly, an echogenic mass in the left lateral ventricle and midline shift of the falx cerebri. Maternal quad screen (serum aneuploidy screening) and cell-free DNA test, tests conducted during pregnancies to assess for birth defect risks, revealed a low risk of aneuploidy. The patient was referred to a maternal–fetal medicine specialty clinic for further evaluation. Amniocentesis was not considered as the DNA test revealed a low risk of aneuploidy and because of patient preference.

Repeat ultrasound at 22 weeks of gestation showed unilateral left ventriculomegaly with midline shift. A 2.4×1.1 cm mass with blood flow in the left ventricle was also visualised. A cranial MRI of the fetus showed a hamartomatous overgrowth of the left cerebral hemisphere involving frontal, parietal, temporal and occipital lobes with a prominent asymmetric germinal matrix (shown in figure 1A). These findings established a diagnosis of HME. Counselling was offered for termination of pregnancy at this time, given delivery and postdelivery risks; however, the parents did not want to consider pregnancy termination. The patient and patients’ family members attended multiple multidisciplinary screening visits from this stage of pregnancy. The multidisciplinary team included an ultrasound team, obstetrics/gynaecology, neonatology and neurology. During these visits, it was agreed that labour would proceed naturally, given her history of a successful vaginal birth. It was understood that on birth, the baby may have seizures and would need neurological intensive care support.

Ultrasound measurements at 26 weeks of gestation revealed severe unilateral ventriculomegaly, measuring 2 cm with midline shift; head circumference was estimated at 267 mm. At 30 weeks of gestation, the left lateral ventricle measured 2.9 cm with midline shift and total head circumference estimated at 308 mm (>97th percentile). At this point, estimated fetal weight was in the 79th percentile. An ultrasound at 36 weeks of gestation is shown in figure 1B. Observing the trend of increasing head circumference, an induction of labour was planned at 37 weeks to optimise the opportunity for vaginal delivery.

The first stage of labour lasted approximately 6 hours and 10 min. Cervical ripening was accomplished with misoprostol, and labour was subsequently augmented with oxytocin/artificial rupture of membranes. The patient received an epidural for pain management. The second stage of labour lasted approximately 41 min. During this stage, the patient had a fever of 39.1°C and persistent category II fetal heart tracings with fetal tachycardia. There was no cephalopelvic disproportion. Due to the maternal fever and persistent category II fetal heart tracings with tachycardia, an operative delivery with vacuum assist was performed which successfully expedited the second stage. The decision to proceed with operative vaginal delivery in the setting of this known fetal neurological anomaly is not well described in the literature. As maternal outcomes were prioritised for clinical management, the team moved forward with vaginal delivery instead of an emergency caesarian section during the second stage of labour. Vacuum was used instead of forceps per ease of use by the provider. The fetal head presented in the left occiput position; a Kiwi Omni Cup (mushroom) vacuum cup was applied to the fetal head 2 cm posterior to the anterior fontanelle. With maternal effort, suction was established; traction adjustments then led to successful delivery. Umbilical artery pCO₂ and pO₂ were found to be 52.9 and 30.2 mm Hg, respectively, with a base excess of −5.6 mmol/L. The third stage of labour lasted approximately 10 min and the postpartum course was uncomplicated. No vascular malformations of the skin or cutis marmorata were noted on initial neonatal examination.

Investigations

In order to determine the aetiology of HME, a genetic test was performed which identified megalencephaly–capillary malformation syndrome due to a somatic variant in the PIK3CA–mTOR (mammalian target of rapamycin) pathway.

Differential diagnosis

HME is primarily differentiated from its chief differential diagnoses of ventriculomegaly and macrocephaly by ultrasound. Fetuses with HME have an isolated increase in size of one hemisphere of the brain, whereas ventriculomegaly and macrocephaly have symmetrical increases in ventricular and head size, respectively. While megalencephaly and HME share similar brain overgrowth patterns, HME demonstrates unilateral hemispheric malformation/growth; this can be better visualised on a fetal MRI. While hydrocephalus (buildup of fluid in the ventricles of the brain) will present with similar ventriculomegaly findings on ultrasound scan, HME will demonstrate unilateral hamartomatous overgrowth visualised in fetal MRI. Diagnoses such as obstructing masses, intracranial haemorrhage, dural sinus thrombosis and arteriovenous malformations are difficult on fetal ultrasound but may be excluded by fetal MRI. Other congenital disorders such as Chiari II malformation, Dandy-Walker syndrome, and aqueductal stenosis demonstrate structural differences on MRI unique to the cerebellum or posterior neural structures. Findings such as dysplasias may be excluded through clinical presentation of facial features and X-ray findings of the cranial base/skull. Blood testing may be informative in the exclusion of infectious aetiologies. Lastly, rare syndromes such as Proteus syndrome may present with symptoms of HME. However, this can be excluded through genetic testing of AKT1 mutation or clinical presentation showing physical growth outside of the brain (extremities, etc).

Outcome and follow-up

The neonate was born with a length of 48.7 cm, weight of 2.973 kg and Apgar scores of 8 and 9 at 1 and 5 min, respectively. She was admitted to the neonatal intensive care unit for 5 days and 12 hours, where seizures were noted with frequent left frontal and right parietal interictal epileptiform discharges on electroencephalogram (EEG). Seizures were diagnosed during her first few hours of life, and she was subsequently treated with phenobarbital at 4 mg/kg/day (6 mg every 12 hours). The patient had no respiratory morbidity during the newborn period and was on room air throughout her stay in the neonatal intensive care unit. The neonate was followed up with abdominal ultrasound, MRI of the head, EEG, ECG, echocardiogram, hearing screening, and laboratory tests including direct Coombs/gases test. Alongside the hemimegaloencephaly findings on MRI, tympanometry findings suggested bilateral middle ear dysfunction. Genetic analysis confirmed the neonate developed megalencephaly–capillary malformation syndrome from a somatic variant in the PIK3CA–mTOR pathway. In the month and a half since birth, the neonate failed hearing screening and has had continued seizures, which have been managed with phenobarbital.