|Ahead of print
A rare case of alobar holoprosencephaly with normal facies
Prashant Raj Singh, Raghavendra Kumar Sharma, Lokesh Nehete
Department of Neurosurgery, All India Institute of Medical Science, Raipur, Chhattisgarh, India
|Date of Submission||23-Sep-2020|
|Date of Decision||22-Nov-2020|
|Date of Acceptance||19-Dec-2020|
|Date of Web Publication||19-Jul-2021|
Department of Neurosurgery, All India Institute of Medical Science, Raipur, Chhattisgarh.
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Alobar holoprosencephaly is a rare disorder of brain development. Most of the cases have facial abnormalities and the survival of such children is usually not prolonged. Case Description: We are reporting a 2-month-old female child presented with seizures and delayed developmental milestones. Interestingly, she has no facial abnormality which is quite unusual. The management of such children is difficult and individualized. Conclusion: The counseling of the parents should be done regarding the severity and outcome of such congenital disease and also the importance of the antenatal check-up during a future pregnancy.
Keywords: Facial dysmorphism, fused diencephalon, holoprosencephaly
| Introduction|| |
Holoprosencephaly is a developmental disorder due to impaired midline cleavage of the embryonic forebrain. Three types of holoprosencephaly are alobar, semi lobar, and lobar.
In AH, there is a failure of cleavage of the prosencephalon sagittally into cerebral hemispheres, transversely into telencephalon and diencephalon, and horizontally into olfactory tracts and bulbs. As a result, a small monoventricular cerebrum lacks interhemispheric division. The thalami and the corpora striata are fused across the midline. Olfactory tracts and bulbs, corpus callosum is absent.,, Alobar holoprosencephaly (AH) usually has various facial dysmorphisms which have higher incidence as 80% in such patients and may be nondiagnostic in 20% of the patients., There are very few reported cases of AH with normal facies in the literature. We are reporting a female infant child with AH with normal facial features.
| Case Report|| |
A 2-month-old female child presented to the neurosurgery outdoor clinic with poor feeding, poor activity, and one episode of convulsion. She had no history of fever, neck stiffness, or previous episode of seizure. Her developmental milestones were grossly delayed as told by the mother. Her birth history was insignificant with no history of delayed cry or neonatal illness. Normal non-institutional delivery was carried out at term. Her mother had an unsuccessful attempt for termination of pregnancy with self-consumption of local aborticide medication in the second month of gestation, although no history of diabetes mellitus, radiation exposure, and alcohol intake was present. Regular antenatal check-ups including ultrasonography were not done due to financial constrain and poor educational status.
On examination, the child was crying but consolable, had minimal movements of all four limbs with spasticity. Anterior fontanelle was opened and lax, with 38cm head circumference. No obvious facial and orbital abnormalities were present. The child vitals were within normal limits with normal pulse rate and no irregularities in breathing pattern. No signs of dehydration were present. Developmental milestones were delayed with no neck holding, no cooing, not following the moving light objects, and did not respond to facial expressions. Her computed tomography (CT) brain showed agenesis of the cerebrum, corpus callosum, absent falx cerebri, and fused diencephalic structures with large cerebrospinal fluid filled cavity [Figure 1]. Posterior fossa abnormalities could not be properly differentiated on the CT brain [Figure 1]. Imaging features suggest AH. Patient was planned for magnetic resonance imaging (MRI) and hematological tests to look for any endocrinal abnormalities. But her relatives were not willing for further evaluation. Further genetic workup also could not be done due to non-availability in our institute and unwillingness of the parents of the child. Seizures were well controlled on syrup valproate at 1-month follow up.
|Figure 1: Noncontrast enhancing computer tomography (CT) scan. (A) Axial cuts showing fused diencephalic structures, absent ventricular anatomy in supra, and an infratentorial compartment with undifferentiated posterior fossa. (B) Axial cuts showing very thin cortico-mental thickness with single cerebrospinal fluid-filled cavity with agenesis of the cerebrum, corpus callosum, and absent falx cerebri. (C) Coronal cuts showing normal orbital and nasal anatomy|
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| Discussion|| |
Holoprosencephaly has heterogeneous etiology and the genetic cause is responsible for 15–20% of cases. Common chromosomal abnormalities associated with it are trisomy 13, del (13q), trisomy 18, and del (18p); while most commonly mutated gene associated is SHH (7q36) and is seen in 17% familiar and 3.7% sporadic cases., Maternal diabetes, alcohol intake, cytomegalovirus infection, salicylates, antiepileptic medications, retinoic acid, misoprostol, methotrexate, and cholesterol-lowering agents are also found to be associated with holoprosencephaly., In our case, the unknown drug which was ingested by the mother for terminating the pregnancy would be a causative agent for AH.
Children with AH have many neurological disorders including mental retardation, delayed psychomotor development, spasticity, athetoid movements, and seizure while endocrine disorders may also accompany it., The common findings are central diabetes insipidus which usually present with irritability and dehydration and they may have hypothyroidism and even panhypopituitarism., Other associated anomalies may be renal dysplasia, adrenal dysplasia, renal cyst, intestinal abnormalities, cardiovascular malformations, club foot, spina bifida, or meningocele.
Phenotypic features and its associations
Cyclpoia, ethmocephaly, and cebocephaly are commonly associated with AH and survival is usually 1 week when all these three features are present., Other lesser severe facial abnormalities include premaxillary agenesis, midface hypoplasia, coloboma, hypotelorism, unilateral or bilateral clefts, micropthalmia, solitary central incisor, pyrifrom aperture stenosis, or may have normal facies, which are usually associated with semilobar/lobar holoprosencephaly and very rarely with the AH., In case of lesser severe facial abnormalities, child may survive for less than 4–5 months and only 20–30% will survive around 1 year of life., These facial abnormalities also showed association with the various types of familial inheritance. Autosomal recessive trait has been noted in many cases of normal facies with AH; while it may be sporadic or may be associated with the infant of the diabetic mother.
The prenatal diagnosis of AH with the ultrasound can be confirmed in the first trimester and helped in differentiating it from dorsal ventricular cyst and dandy walker malformation and other similar common causes of hydrocephalus., If a midline “monoventricle” is present and the typical echogenic “butterfly” sign corresponding to the choroid plexuses is absent on fetal head ultrasound, diagnosis of holoprosencephaly should be strongly suspected while AH can be easily confirmed with its finding of monoventricular cerebrum with absent midline structures. Fetal MRI is of importance in case of semi/lobar holoprosencephaly to establish the diagnosis.
These patients are usually managed with symptomatic medication, physiotherapy, and supportive nursing care. Few patients may require cerebrospinal fluid diversion procedures such as ventriculoperitoneal (VP) shunt for symptomatic hydrocephalus in AH but the unique complications as cerebral retroflexion and partial bone collapse owing to the overdrainage has been reported in the literature. To avoid such complications, the recommendation of programmable VP shunt has been favored., This patient’s seizure was well controlled on antiepileptic medication, supported by the literature that seizures in AH were easily controllable on drugs.
AH have such higher mortality which depends on the certain factors as brain developmental malformation severity, facial abnormalities, associated chromosomal abnormalities, and other multiple organ involvement., Long-term survival has been noted in approximately 62 cases while maximum age of the surviving child was 11 years., Karyoptyping is not essential to confirm the diagnosis of AH but it may help in counseling the parents regarding the advent risk of propagating it.
| Conclusion|| |
AH has a very grave prognosis and poor survival. The role of parent’s counseling emphasizing the prognosis of the disease, education regarding care of the child, and need of the antenatal check-up in a future pregnancy to diagnose congenital anomalies early in pregnancy is of utmost importance. The kayotypic analysis should also be encouraged to analyze the risk of acquiring it in future pregnancy.
We certify that the content of this manuscript, in part or in full, has not been submitted to any other journal in any form, and its publication have been approved by all co-authors.
Financial support and sponsorship
Conflicts of interest
The authors have no financial conflict of interest to disclose.
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