Alobar Holoprosencephaly and Cebocephaly in a Newborn

A term, female neonate was referred to us on 2nd postnatal day with complaints of respiratory distress and multiple congenital anomalies. The child was delivered vaginally at term, with no history of birth asphyxia, with a birth weight of 1.8 kg, born out of nonconsanguineous marriage, to a 25-year-old primigravida. There was no significant antenatal illness or drug intake. The anomaly scan at 24 weeks of gestation revealed monoventricle, fused thalamus, absent corpus callosum, absent inter-hemispheric fissure, absent cavum septi pellucidi, and absent third ventricle with decreased inter orbicular distance suggestive of alobar holoprosencephaly (HPE). The parents had been informed about the prognosis, and medical termination of pregnancy was offered, but the parents decided to continue with the pregnancy. On examination, the baby was pink, with good cry and activity, temperature of 36.5°C, heart rate 152/min, respiratory rate 62/min, SpO2 84% in room air, capillary refill time of 2 seconds, and blood pressure of 62/44/32 mm Hg. The weight (1.8 kg), length (43 cm), and head circumference (29 cm), were all <3rd centile, indicating symmetrical intrauterine growth retardation (ponderal index 2.26). There was craniosynostosis with very small anterior fontanelle, microphthalmia, hypertelorism, left-sided unilateral partial cleft palate, and single nasal cavity without nasal septum [Figure 1]. The limbs, digits, ears and neonatal reflexes were normal. The child had minimum respiratory distress (Downe score 2), and normal cardiovascular and abdominal examination.Figure 1: Baby showing microcephaly, micrognathia, retrognathia, single nasal cavity without nasal septum, hypotelorism, and cebocephalyThe baby was started on oxygen by hood along with maintenance fluids. Routine blood investigations including septic screen were normal. The respiratory distress settled, oxygen support was gradually stopped by the 4th day of life. The baby was started on feeds by orogastric tube on day 3 followed by paladai feeding. A noncontrast computed tomography of head showed a dilated ventricular system with bilateral lateral ventricles communicating with each other forming a single cavity. The cerebral mantle was seen communicating anteriorly with a small rim of cortex surrounding the central mono ventricle. There was no visualization of interhemispheric fissure, third ventricle and corpus callosum with fusion of bilateral thalami in the midline- findings suggestive of HPE continuum, likely alobar variant [Figure 2a-c]. The scan also revealed absent bony septum with single nasal cavity, significantly reduced inter orbital distance as compared to inter ocular diameter suggestive of hypotelorism [Figure 3]. The ultrasonography of the abdomen showed no significant abnormalities except absent right ovary. Echocardiography was normal. Ophthalmological examination revealed normal lens, and fundus, besides microphthalmia with microcornea. Karyotyping revealed normal 46XX. Thus, a diagnosis of alobar HPE and cebocephaly with left-sided unilateral partial cleft palate was made. The parents were counseled and the baby was discharged on day 14 of life. On 2-months follow-up, the baby had developed signs of evolving spastic quadriplegic cerebral palsy [Figure 4]. She was advised physiotherapy.Figure 2: (a) Axial section of brain showing a large monoventricle with a small rim cortex seen anteriorly and absent interhemispheric fissure. (b) Axial section of brain showing fused thalamus and absent interhemispheric fissure. (c) Mid sagittal section of brain showing absence of corpus callosum and third ventricleFigure 3: Axial section of face showing single nasal cavity with absent nasal septumFigure 4: On follow up of the baby at 2 months of life the baby has developed spasticity in all 4 limbs, scissoring of lower limbs and cortical thumb and fisting indicating signs of evolving spastic quadriplegic cerebral palsyHoloprosencephaly refers to a spectrum of central nervous system malformations that result from a primary defect in the normal median cleavage of embryonic forebrain involving moulding of the rostral neural tube during early embryogenesis.[1] It is rare with an estimated incidence of 1 in 16,000 live births with female preponderance more in isolated cases.[2] Environmental causes include diabetes, maternal alcoholism, intrauterine infection and certain medications (retinoic acid, cholesterol synthesis inhibitors),[3] none being present in our case. Genetically, HPE may be inherited in an autosomal dominant manner, with at least 17 genes of which SHH, ZIC2, GLI2, SIX3, FGF8 and FGFR1 are common; familial HPE being mostly due to mutation in SHH gene.[2] Trisomy 13 is the most common chromosomal abnormality associated with HPE. Other syndromes associated with HPE include Smith–Lemli–Opitz syndrome, Pallister–Hall syndrome, and Velo-cardio facial syndrome.[2] Most cases, like ours, are isolated and sporadic with normal karyotype. Clinical presentation of HPE depends on the severity of involvement. The classical types of HPE in decreasing order of severity are alobar, semi-lobar, lobar, and interhemispheric variants.[4] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.