Holoprosencephaly is a complex intracranial abnormality characterized by absent or incomplete cleavage of the prosencephalon. It has been roughly categorized into 3 types (from most severe to least severe): (1) alobar holoprosencephaly, or complete absence of midline forebrain division resulting in a monoventricle and fused cerebral hemispheres; (2) semilobar holoprosencephaly, or incomplete forebrain division resulting in partial separation of cerebral hemispheres, typically posteriorly; and (3) lobar holoprosencephaly, or complete ventricular separation with focal areas of incomplete cortical division or anterior falcine hypoplasia.
Alobar form is rare autosomal recessive malformation consisting of large holospheric brain. Alobar holoprosencephaly is characterized by nearly complete lack of ventricular and hemispheric cleavage. The brain is basically an undifferentiated holosphere with central monoventricle and fused thalami.
From a genetic point of view all holoprosencephalies have the same significance. Their frequency is estimated at 1 in 16,000 to 1 in 18,000 births. Holoprosencephalies have a heterogenous cause; chromosomal aberration is found in about one half of the cases. Chromosome 13 is most frequently involved. Partial deletion of chromosome 13 as well as trisomy may coexist with holoprosencephalies.
Naguib (1992) undertook a clinical and cytogenetic ascertainment of holoprosencephaly at the Kuwait Maternity Hospital. Of the 16,121 total births, seven patients fulfilled the criteria for holoprosencephaly, giving an incidence of 4.3 per 10,000 births. This rate was four-times higher than that recorded in previous years. Male to female ratio was found to be 1.3:1. Parental consanguinity was recorded in two patients. All, except one case, were sporadic; the exception having a family history of the condition with two affected siblings. In one patient, chromosomal study identified a variant in the Y chromosome. All other cases showed normal results in the chromosome analysis.
[Naguib KK. Holoprosencephaly clustering in Kuwait. Bull High Inst Public Health. 1992; 22(1):117-24.]
Sawardekar (2005) conducted a study to establish the prevalence of major congenital malformations in children born during a 10-year period in Nizwa Hospital. Of the 21,988 total births in the hospital, three children were born with holoprosencephaly sequence. Sawardekar (2005) hinted for a possible genetic contribution in these children.
Rejjal et al. (1994) studied brain CT scans in twenty-three consecutive patients with congenital choanal atresia (CCA; 10 boys and 13 girls) to determine the prevalence and the scope of associated brain abnormalities. CCA was associated with known syndromes or different congenital abnormalities in 7 and 10 patients, respectively, and was an isolated finding in 6 patients. Six patients (26%) had brain abnormalities including alobar holoprosencephaly, absent corpus callosum, benign enlargement of the subarachnoid space of infancy, cerebral calcification, small right hemisphere, small ventricles and microcephaly.
Al Talabani et al. (1998) studied the pattern of major congenital malformations in 24,233 consecutive live and stillbirth at Corniche hospital, which is the only maternity hospital in Abu Dhabi, between years 1992 and 1995. A total of 401 babies (16.6/1,000), including 289 Arabs, were seen with major malformation. Sporadic conditions accounted for 26% of the cases. In their study, Al Talabani et al. (1998) observed one case of holoprosencephaly in a family from the United Arab Emirates with no recurrence in other members of the family. Al Talabani et al. (1998) concluded that their study was very close to representing the true incidence of congenital abnormalities in the whole United Arab Emirates, as they investigated over 98% of deliveries in Abu Dhabi, the capital of United Arab Emirates.
Sztriha et al. (1998) described an infant who had a combination of lobar holoprosencephaly and open-lip schizencephaly. Midline fusion of the basal ganglia was associated with bilateral absence of abundant parts of the brain mantle. Agenesis of the corpus callosum, hypoplasia of the optic nerves and chiasm, absence of the septum pellucidum, posterior pituitary and olfactory bulbs were further components of the malformation. Blindness, intractable seizures, spastic tetraplegia, somatomental retardation and diabetes insipidus were the main clinical features. Sztriha et al. (1998) suggested that defect in the induction of the mediobasal part of the prosencephalon and failure of cell proliferation can be responsible for this complex malformation.
In 1999, Al-Gazali et al. conducted a retrospective study on 9610 births in the three major hospitals in the city of Al-Ain between October 1995 and January 1997. Of the 225 babies with congenital anomalies identified, 31 had CNS abnormalities (3.2/1000). Syndromic abnormalities of the CNS were present in 13 cases (42%), chromosomal abnormalities in one case (3.2%) and the rest included: neural tube defect (NTD) in 11 cases (36%), holoprosencephaly in two cases (6.4%) and hydrocephalus in four cases (12.9%). The incidence rate for holoprosencephaly in the United Arab Emirates for the studied period was calculated at 0.2 per 1000 births.