Introduction

Holoprosencephaly (HPE) is a congenital developmental disorder in which the forebrain fails to form normally during early embryogenesis, resulting in a spectrum of brain and craniofacial abnormalities [1,2]. It is the most common structural anomaly of the developing forebrain and is characterized by incomplete midline cleavage of the prosencephalon, meaning the primitive forebrain fails to divide completely into the right and left cerebral hemispheres [1,2]. The severity of this abnormal separation varies, ranging from partial to complete fusion of the cerebral hemispheres and other midline structures such as the corpus callosum, basal ganglia, and hypothalamus. Because the forebrain and midface both arise from the prechordal mesoderm, many patients with HPE also exhibit craniofacial abnormalities, including cleft lip and palate, microcephaly, microphthalmia, and cyclopia [2,3]. The development of HPE is multifactorial, with both genetic and environmental contributors, including maternal diabetes mellitus, in utero exposure to toxins, medications, infections, aneuploidy, and other genetic abnormalities [2,3].

HPE is classically divided into four subtypes based on the degree of nonseparation of the prosencephalon: alobar, semilobar, lobar, and the middle interhemispheric (MIH) variant, also known as syntelencephaly [1]. Originally described by Barkovich and Quint in 1993, syntelencephaly is a rare subtype of HPE characterized by an abnormal midline connection between the posterior parts of the frontal lobes and anterior parts of the parietal lobes, often accompanied by absence of the body of the corpus callosum [4]. Additional common findings include fusion of the thalami and caudate nuclei, gray matter heterotopias, cortical dysplasia, and an azygos anterior cerebral artery [1,4,5]. It is postulated to result from diminished migration of the mesenchyme to the midportion of the developing telencephalon due to ineffective mesenchymal production by the prechordal plate [4]. Recognition of HPE and its subtypes is clinically important because of the potential for significant neurologic, endocrine, visual, feeding, and developmental complications. These manifestations contribute substantially to morbidity and, in more severe forms of HPE, mortality, necessitating multidisciplinary evaluation, individualized management, and long-term follow-up.

Septo-optic dysplasia is a related congenital disorder characterized by abnormalities of midline brain development, underdevelopment of one or both optic nerves that can result in visual impairment or blindness, and pituitary dysfunction leading to endocrine abnormalities such as growth hormone deficiency, hypothyroidism, adrenal insufficiency, or diabetes insipidus [6]. The diagnosis is established when at least two of these three features are present [6]. Because visual and endocrine abnormalities may not be apparent at birth and can evolve over time, early recognition is essential to facilitate multidisciplinary management, hormone replacement when indicated, visual rehabilitation, and long-term surveillance to reduce morbidity.