Neuroradiological findings of trisomy 13 in a rare long-term survivor

Abstract

Patau syndrome remains a difficult diagnosis for parents and a challenging conversation for clinicians due to the overall poor prognosis. Previous population-based reports have documented the sobering life expectancies of these patients, with few surviving to 1 year of age. Despite the high mortality rate in infants born with trisomy 13, there are several reports of survival into late childhood and early adulthood. While clinical outcomes have been well documented, there has been a paucity of literature describing postnatal imaging findings in long-term survivors. We present a case report of a 2-year-old girl with trisomy 13 who underwent brain magnetic resonance imaging examination at our institution to evaluate for possible structural abnormalities contributing to central sleep apnea. We describe the clinical and postnatal neuroimaging findings of this rare patient with trisomy 13. Understanding the spectrum of neuroradiological findings in long-term survivors with trisomy 13, in combination with other organ system abnormalities, could add important clinical information and help better predict patient outcomes and expectations among parents.

Introduction

Trisomy 13, or Patau syndrome, is a rare chromosomal anomaly with an incidence of approximately 1 in 5000 to 1 in 20,000 live births.^1,2 It is the third most common autosomal triploidy in liveborn infants, after trisomy 21 and 18. Patau syndrome is the most lethal of all the viable trisomies, with most resulting in spontaneous abortion, fetal demise, or stillbirths. Those that do survive to birth typically die in the early postnatal period as emphasized by a median survival age of 2.5 to 8.5 days.^3–5 Recent data show that only 9.7% of children with trisomy 13 reach 5 years of age.⁶ There are rare reported cases of these patients surviving into late childhood and early adulthood, with the oldest documented survivor reaching 19 years of age.⁷

There are well documented imaging findings in patients with Patau syndrome, which primarily come from in utero ultrasound in the obstetrics and gynecology literature. Classically described distinguishing syndromic features are largely a result of malformations of midline development and include holoprosencephaly, cleft lip/palate, structural ocular abnormalities, Dandy Walker malformation, hydrocephalus, agenesis of the corpus callosum, neural tube defects, and cardiac anomalies. Postaxial polydactyly is another common finding that can be seen in prenatal ultrasound examinations.

We present a case of trisomy 13 in a 2-year-old girl who underwent magnetic resonance imaging (MRI) examination of the brain to assess for structural abnormalities contributing to clinically diagnosed central sleep apnea. This case report provides a rare insight into the intracranial manifestations of this syndrome with high resolution MRI. To the best of our knowledge, there are no peer-reviewed papers describing postnatal neuroimaging findings of full trisomy 13 using MRI.

Clinical presentation

A 2-year-old girl presented to our radiology department for MRI examination of the brain to assess for structural abnormalities contributing to central sleep apnea. The patient’s medical history consisted of a full-term delivery with prenatal ultrasound remarkable for a prominent gallbladder, duplicated superior vena cava, decreased abdominal circumference, nuchal cord, and oligohydramnios. Initial neonatal physical examination demonstrated borderline microcephaly, short back-sloping forehead, deep-set orbits, bulbous nose with crease above the nasal root, low-set ears, intact palate, single transverse palmar crease, tapered fingers, and squared great toes. Based on the prenatal ultrasound findings and dysmorphic features on physical examination, an underlying genetic syndrome was suspected. Subsequent chromosomal analysis (30 cells were counted) confirmed complete trisomy 13 without translocation or mosaicism.

The patient had several medical problems since birth, primarily related to congestive heart failure from multiple congenital cardiac defects discovered postnatally, including atrial and ventricular septal defects as well as bicuspid aortic valve. Gastrointestinal problems included small bowel malrotation and gastroesophageal reflux requiring Nissen fundoplication. Neurological problems included epilepsy and developmental delay. Following surgical repair of the cardiac anomalies, the patient began experiencing apneic spells and was subsequently diagnosed with severe central sleep apnea. This led to further investigation with brain MRI to assess for contributing structural brain abnormalities such as a Chiari I malformation.

Imaging

An MRI scan of the brain was performed without intravenous contrast with the indication to evaluate for structural abnormalities to explain chronic central sleep apnea. A standard complement of pulse sequences was performed including three-dimensional gradient-recalled echo T1-weighted, fast spin echo T2-weighted, and T2-fluid-attenuated inversion recovery sequences in multiple planes. Images demonstrated several intracranial abnormalities (Figure 1). Notably, however, the cerebral hemispheric separation was normal without holoprosencephaly. The cerebral gyral and myelination pattern was age appropriate. The ventricles were thin and elongated with a somewhat parallel morphology at the level of the posterior body. The corpus callosum was mildly hypoplastic, primarily manifested by decreased anterior–posterior dimension. The cerebellum was dysmorphic with abnormal foliation pattern and superior vermian hypoplasia. A large cisterna magna was also present. There was severe microphthalmia bilaterally. In addition, a triangular band of tissue was seen from the posterior aspect of the lens to the optic disc consistent with persistent hyperplastic primary vitreous. This results from failure of regression of the embryonic hyaloid vascular system.

Figure 1.

Sagittal T1-weighted image (a) demonstrates mild hypoplasia of the corpus callosum with decreased anterior–posterior length. Axial T2-weighted images (b and c) depict normal cerebral hemispheric sulcation, gyration and myelination pattern for age. There is a dysmorphic appearance of the posterior body of the lateral ventricles which appear mildly elongated. There is abnormal foliation pattern of the superior cerebellar hemispheres with cerebellar vermian hypoplasia. At the level of the orbits (c), there is severe microphthalmia bilaterally with a triangular band of tissue spanning from the posterior aspect of the lens to the optic disc consistent with persistent hyperplastic primary vitreous.

Discussion

Patau syndrome remains an often lethal diagnosis with most dying in utero or in the first few days after birth. Several studies have assessed survival in trisomy 13, the results of which emphasize the dismal prognosis. As expected, there is a clear survival difference based on whether the diagnosis was made in the prenatal or postnatal period. In those diagnosed prenatally, 96% had died by the end of the first week of life. With a postnatal diagnosis, survival is slightly better with 3–10% of patients alive by the end of the first 5 years of life.^1,2,6–8 The variability in patient survival is not fully understood but possible contributing factors include race, gender, genetic mosaicism or translocations, variable expressivity, among others.

A wide spectrum of clinical manifestations and expressivity has been described, accounting for the variability in patient survival. Similarly, differences in imaging findings in patients with trisomy 13 are also common and, predictably, the number and severity of anomalies often directly correlates with survival.⁹ Structural abnormalities of the central nervous system (CNS) are abundant with the hallmark being the holoprosencephaly spectrum as well as other anomalies of midline development, particularly agenesis of the corpus callosum. Other described CNS defects include cerebellar hypoplasia, enlarged cisterna magna, ventriculomegaly, and neural tube defects. Craniofacial abnormalities include microcephaly, cleft lip/palate, microphthalmia, and hypotelorism. A prenatal ultrasound review of 33 patients with trisomy 13 showed the prevalence of various ultrasound abnormalities: holoprosencephaly (33%), large cisterna magna (18%), cerebral ventricular dilatation (9%), facial anomalies (48%), renal (33%) and cardiac (48%) defects [10]. Few reports exist describing CNS anomalies in long-term survivors using cross-sectional imaging, and fewer still with MRI. A report of a 7-year-old boy with mosaic trisomy 13 who underwent MRI examination demonstrated ventriculomegaly, hypoplasia of the septum pellucidum, and thinning of the splenium of the corpus callosum.¹¹ Another report of an 11-year-old survivor with trisomy 13 briefly described computed tomography findings including mild cortical and cerebellar vermis superior atrophy.¹²

Our case of a 2-year-old girl with trisomy 13 demonstrated relatively mild morphological CNS manifestations of this syndrome, including cerebellar dysmorphism, corpus callosum hypoplasia, abnormal ventricular morphology, microphthalmia, and persistent hyperplastic primary vitreous. This case provides a unique insight into the spectrum of CNS findings in a rare, relatively long-term survivor with high quality MRI. Understanding the spectrum of neuroradiological findings in long-term survivors with trisomy 13, together with other organ system abnormalities, could add important clinical information. In particular, it may help better predict patient outcomes and overall patient functioning in addition to potentially assisting in expectation discussions with parents.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.