Ethmocephaly: A rare cephalic disorder.

Dear Sir,

A male neonate, product of nonconsanguineous marriage, was delivered vaginally with severe birth asphyxia (Apgar score 3, 4, 6) to a primiparous woman at 36 weeks’ gestation. The mother did not have any medical illness during pregnancy, and an antenatal ultrasound was performed at 29 weeks’ gestation which revealed holoprosencephaly with midline facial defect in the fetus. Examination after birth revealed weight of 2.6 kg, head circumference 31 cm (<3rd centile), facial dysmorphism (bilateral cleft lip, incomplete cleft palate, a central proboscis with a single nare, hypoplastic eyeballs, low-set ears), short neck with low hairline, widely spaced nipples, sandal gap in both feet, and bilateral simian crease [Figure 1]. He also had a large anterior fontanelle with widely separated sutures. The neonate received resuscitation at birth and was shifted to neonatal intensive care unit. He was put on mechanical ventilation and supportive therapy. Ultrasound of the head revealed undivided cerebral hemispheres with a single ventricle. Our neonate expired at 12 h of life following cardiorespiratory arrest. Karyotyping was performed which was reported as normal.

Figure 1

Neonate with bilateral cleft lip, cleft palate, and a central proboscis with single nare and low set ears

Ethmocephaly is the rarest phenotypic variant of a group of defects called the holoprosencephaly (HPE) malformation sequence;[1] other variants include cebocephaly, cyclopia, and median cleft palate. HPE is a cephalic disorder characterized by congenital brain malformation due to incomplete cleavage of the prosencephalon occurring between the 18th and 28th day of gestation. HPE is categorized into three levels of increasing severity: Lobar (where the right and left ventricles are separated, but with some continuity across the frontal cortex); semilobar (partial separation of hemispheres), and the most severe form alobar HPE (single brain ventricle and no interhemispheric fissure).[2]

HPE can be caused by both genetic and environmental factors such as maternal insulin-dependent diabetes mellitus (1% risk of HPE),[3] maternal alcoholism, prenatal exposure to teratogens (alcohol, retinoic acid, cholesterol biosynthesis inhibitors, and maternal infections (cytomegalovirus, toxoplasmosis, rubella).[4] Some genetic associations with trisomy 13 or 18 have been reported.[5] Multiple malformation syndromes such as Kallmann syndrome, Pallister–Hall, Smith–Lemli–Opitz, and CHARGE syndrome have been found to be associated with HPE. However, nearly 70% cases are sporadic. Nearly all HPE malformation disorders have a fatal outcome during gestation or in early infancy. HPE can be detected by ultrasonography in the first trimester. Ultrasonographic markers include hypertelorism and a single common cerebral ventricle with absent midline echo. Other investigations include chromosomal analysis by karyotyping and genetic mutation analysis by denaturing high-performance liquid chromatography and multiplex polymerase chain reaction.

Ethmocephaly is a rare cephalic disorder with a reported incidence of 1 in 15,000 among live births and 1 in 250 among abortuses.[1] It characterized by HPE with an undivided cerebrum and a single ventricle. In addition, there is a midline facial anomaly associated with a central proboscis, two well-formed orbits with absent or hypoplastic eyeballs, hypotelorism, and low set ears. It is differentiated from other HPE disorders namely cyclopia where the two eyes are fused together in a single median orbit and from cebocephaly which is characterized by a flattened nose with single nostril located below close-set eyes, based on the phenotype. Our case presented with midline facial defects, hypotelorism, bilateral microphthalmos, a central proboscis and bilateral low set ears, and alobar HPE, which are characteristic of ethmocephaly.

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.