This disorder consists of a spectrum of defects or malformations of the brain and face. Most cases are associated with severe malformations of the brain that are incompatible with life and often cause Spontaneous intrauterine death. At the other end of the spectrum are individuals with facial defects that affect the eyes, nose, and upper lip and normal or near-normal brain development. Seizures and Mental retardation may occur.
The most severe of the facial anomalies is Cyclopia, an abnormality characterized by a single eye, located in the area normally occupied by the root of the nose, and a missing nose or a nose in the form of a proboscis a tubular appendage, located above the eye. Ethmocephaly is the least common facial anomaly. It consists of a proboscis separating narrow-set eyes with an absent nose and microphthalmia. Cebocephaly, another facial anomaly, is characterized by a small-flattened nose with a single nostril situated below incomplete or underdeveloped closely set eyes.
The least severe in the spectrum of facial anomalies is the Median cleft lip also called premaxillary agenesis. Symptoms of Holoprosencephaly may vary on an individual basis for each patient. (NINDS) Diagnosis: Prenatal diagnosis of agnathia-holoprosencephaly: three-dimensional imaging by helical computed tomography. Ultrasound is an important method for diagnosis of HE. A case of agnathia-holoprosencephaly, which was prenatally diagnosed, based on helical computed tomography (CT) images obtained at 23 weeks of gestation.
Ultrasound examination first showed the presence of alobar holoprosencephaly, but the facial structures were not clearly detailed. However, three-dimensional imaging by helical CT precisely demonstrated the most striking feature of agnathia: absence of the mandible. This technique provided valuable information that contributed to the in utero diagnosis. In utero helical CT is a useful examination tool for the diagnosis of abnormalities. (Ebina Y et al. ) Study for diagnosis of holoprosencephaly by sonography in first trimester: Objective was to describe the experience with sonographic diagnosis of fetal holoprosencephaly in first trimester.
A total of three fetuses with early prenatal diagnosis of holoprosencephaly were sonographically evaluated and followed up. Results of the study revealed that all showed monoventricular cavity, fused thalami, no falx and cavum septum pellucidum. All of them were correctly diagnosed sonographically in the first trimester. Extra cranial anomalies had also been identified in all three fetuses and all of them had facial abnormalities. Conclusion was that this small series indicated that holoprosencephaly could be diagnosed in the first trimester. (Tongsong T. et al1999, vol. 66, pp. 165-169 )
Discussion: Treatment is individualized, although common problems occur. In general, there is no standard course of treatment for holoprosencephaly. Treatment is symptomatic and supportive. Each child has a unique degree of malformations. Children who survive, treatment is symptomatic and involvement in support groups and HPE Conferences are helpful although it is possible that improved management of diabetic pregnancies will help prevent holoprosencephaly, there is no means of primary prevention. (NINDS) Prognosis: The prognosis for individuals with the disorder depends on the severity of the brain and facial deformities.
Most of those who survive show no significant developmental gains. The older literature suggested that the prognosis was uniformly poor. Recent studies show a broader range of outcomes than previously assumed. (NIH) Clinical Research and Management on Holoprosencephaly: Research by Hsieh TY, Yu CH, Kuo PL, Chang FM. Prenatal diagnosis of alobar holoprosencephaly with cystic hygroma. Objective: Holoprosencephaly associated with cystic hygroma and hydrops fetalis has never been reported. In this article, a rare case of holoprosencephaly associated with cystic hygroma and hydrops fetalis diagnosed prenatally was reported.
Case report: A 28-year-old woman, gravida 2, para 0, artificial abortion 1, was referred to antenatal clinic at 16 weeks of gestation due to fetal cystic hygroma detected by prenatal routine ultrasonography at a local hospital. In the clinic, single ventricle with fused thalami and cystic mass at the fetal neck as well as hydrops fetalis were noted by level II ultrasound. Under the impression of holoprosencephaly with cystic hygroma and hydrops fetalis, termination of pregnancy with misoprostol was undertaken. The histopathology of fetal autopsy confirmed the diagnosis and disclosed additional intracranial abnormalities.
Conclusion was that the fetus with holoprosencephaly might have other associated structural abnormalities. Cystic hygroma and hydrops fetalis are rare associations. Meticulous sonographic examinations to depict the associated defects are necessary in any fetus with holoprosencephaly. (Hsieh TY, Yu CH, Kuo PL, Chang FM. 2006, 45(2):146-9) Research study by Roesler CP et al Links between abnormal brain structure and cognition in holoprosencephaly. Objective: Converging information on medical issues, motor ability, and cognitive outcomes was essential when addressing long-term clinical management in children with holoprosencephaly.
This study considered whether adding more informative structural indices to classic holoprosencephaly categories would increase prediction of cognitive outcomes. Forty-two children with holoprosencephaly were examined to determine the association of deep gray nuclei abnormalities with cognitive abilities and the effect of motor skill deficits on cognitive performance. Findings indicated that non-separation of the deep gray nuclei was significantly associated with the cognitive construct of vocal communication, but not with the cognitive constructs of social awareness, visual attention, or auditory comprehension.
Importantly, motor skill deficits did not significantly affect performance on the Carter Neuro cognitive Assessment. This study is the first investigation to provide a descriptive overview of specific cognitive skills in this group of children. The results also strongly suggested that this feature of the brain’s structure does not predict all aspects of neuro developmental function. These findings contribute a critical component to the growing body of knowledge regarding the medical and clinical outcomes of children with holoprosencephaly. (Roesler C P et al.
2006, 35(6):387-94) Research study by Yamada S. Embryonic holoprosencephaly: pathology and phenotypic variability. Congenit Anom (Kyoto). Over 200 cases of HPE in the Kyoto Collection of Human Embryos were observed grossly and histologically, with special emphasis on the anomalies of the brain, face and eye. The facial anomalies of HPE human embryos after Carnegie stage (CS) 18 could be classified into cyclopia, synophthalmia, ethmocephaly, cebocephaly, and premaxillary agenesis, similarly as the classical classification for postnatal cases.
On the other hand, HPE embryos at CS 13-17 showed some characteristic facies, which are different from those in older embryos. In this study, pathology and phenotypic variability in HPE embryos were discussed from the embryopathological point of view. It was concluded that HPE is one of the major CNS anomalies, which have been extensively studied, and provides a clue to the mechanisms of normal and abnormal development of craniofacial structures. (Yamada S. 2006 46(4):164-71. ) Conclusion: Ultrasound is an important tool for diagnosis of HE.
Recent research has identified specific genes that cause holoprosencephaly. The knowledge gained from these fundamental studies provides the foundation for understanding how to develop new ways to treat, and potentially prevent, this disorder. Gaining basic knowledge about how the nervous system develops and understanding the role of genetics in fetal development are major goals of scientists studying congenital neurological disorders. Scientists are rapidly learning how harmful insults at various stages of pregnancy can lead to developmental disorders.
Scientists are also concentrating their efforts on understanding the complex processes responsible for normal early development of the brain and nervous system and how the disruption of any of these processes results in congenital anomalies such as cephalic disorders. (NHGRI)
Reference:
Ebina Y, Yamada H, Kato EH, Tanuma F, Shimada S, Cho K, Fujimoto S. Prenatal diagnosis of agnathia-holoprosencephaly: three-dimensional imaging by helical computed tomography. Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, N15 W7, Kita-Ku, Sapporo, Japan. ebiyas@med. hokudai. ac. jp .Copyright 2001 John Wiley & Sons, Ltd. PMID: 11180246 [PubMed – indexed for MEDLINE] Hsieh TY, Yu CH, Kuo PL, Chang FM. Prenatal diagnosis of alobar holoprosencephaly with cystic hygroma. Taiwan J Obstet Gynecol. 2006 Jun;45(2):146-9. PMID: 17197356 [PubMed – indexed for MEDLINE] NHGRI Clinical Research on Holoprosencephaly Clinical and Genetic Studies on Holoprosencephaly [clinicaltrials. gov] National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH) National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland, 20892, United States; Recruiting