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Medicine Jul 2018Holoprosencephaly is a structural malformation of the brain that results from the complete or incomplete noncleavage of the forebrain of the embryo into 2 hemispheres.... (Review)
Review
RATIONALE
Holoprosencephaly is a structural malformation of the brain that results from the complete or incomplete noncleavage of the forebrain of the embryo into 2 hemispheres. We report a severe case of alobar holoprosencephaly diagnosed at 38 weeks, associated with cebocephaly, microcephaly, and craniosynostosis.
PATIENT CONCERN
The main knowledge added by this case is the late ultrasound diagnosis and chromosomal analysis that revealed a very rare abnormality (45X/46,XX/47,XX) with mosaicism at chromosome 18.
DIAGNOSES
Investigation of the mother revealed nothing remarkable from clinical point of view and on laboratory tests. Ultrasonography identified a fetal biometry appropriate for gestational age, except for the head biometry and abdominal circumference, that were appropriate for less than the fifth percentile. Microcephaly, a large midline monoventricle, absent midlinestructures, cleft lip, cebocephaly (hypotelorism, single-nostril nose), ethmocephaly (hypotelorism, interorbital proboscis) and craniosynostosis, were also present. Fetal magnetic resonance imaging of fetus revealed an absent midline structure, a central monoventricle, abnormal corpus calosum, and abnormal gyri.
INTERVENTIONS
A cesarean section at 38 weeks was indicated for fetal bradycardia and a female baby was delivered, with Apgar score 6, weight 2290g. After birth, the diagnosis of the fetus confirmed holoprosencephaly with facial anomalies and demonstrated repeated tonic-clonic seizure, severe respiratory failure, cyanosis, decreased muscle tone, palor, and apnea. Laboratory examination of the newborn revealed acidosis and a prolonged of prothrombin time. The neonate was treated for severe respiratory distress syndrome, with immediate intubation and resuscitation. Vitamin K, fresh frozen plasma, and antibiotics were also administered.
OUTCOMES
After delivery, exitus of the fetus occurred at 3 days and 18hours due to massive pulmonary hemorrhage.
LESSONS
We described a case of alobar holoprosencephaly diagnosed at 38 weeks of gestation and associated with a rare chromosomal abnormality (45X/46,XX/47,XX) with mosaicism at chromosome 18. Emotional implications could have been less severe if the patient underwent regular ultrasonography allowing a diagnosis in the first or early second trimester.
Topics: Abnormalities, Multiple; Brain; Chromosome Disorders; Chromosomes, Human, Pair 18; Craniosynostoses; Delivery, Obstetric; Female; Gestational Age; Holoprosencephaly; Humans; Infant, Newborn; Karyotype; Magnetic Resonance Imaging; Microcephaly; Mosaicism; Pregnancy; Ultrasonography, Prenatal
PubMed: 30024536
DOI: 10.1097/MD.0000000000011521 -
Genetics and Molecular Biology Mar 2014Holoprosencephaly (HPE) is a spectrum of brain and facial malformations primarily reflecting genetic factors, such as chromosomal abnormalities and gene mutations. Here,...
Holoprosencephaly (HPE) is a spectrum of brain and facial malformations primarily reflecting genetic factors, such as chromosomal abnormalities and gene mutations. Here, we present a clinical and molecular analysis of 195 probands with HPE or microforms; approximately 72% of the patients were derived from the Latin American Collaborative Study of Congenital Malformations (ECLAMC), and 82% of the patients were newborns. Alobar HPE was the predominant brain defect in almost all facial defect categories, except for patients without oral cleft and median or lateral oral clefts. Ethmocephaly, cebocephaly, and premaxillary agenesis were primarily observed among female patients. Premaxillary agenesis occurred in six of the nine diabetic mothers. Recurrence of HPE or microform was approximately 19%. The frequency of microdeletions, detected using Multiplex Ligation-dependant Probe Amplification (MLPA) was 17% in patients with a normal karyotype. Cytogenetics or QF-PCR analyses revealed chromosomal anomalies in 27% of the probands. Mutational analyses in genes SHH, ZIC2, SIX3 and TGIF were performed in 119 patients, revealing eight mutations in SHH, two mutations in SIX3 and two mutations in ZIC2. Thus, a detailed clinical description of new HPE cases with identified genetic anomalies might establish genotypic and phenotypic correlations and contribute to the development of additional strategies for the analysis of new cases.
PubMed: 24764759
DOI: 10.1590/s1415-47572014000200011 -
Cureus Jul 2022Alobar holoprosencephaly is a congenital malformation that results from failure of the forebrain/prosencephalon to divide into right and left halves. Despite the...
Antenatal Ultrasonographic Diagnosis of a Constellation of Alobar Holoprosencephaly, Ethmocephaly, and Hydronephrosis in a Case of Early-Onset Intrauterine Growth Retardation: A Case Report.
Alobar holoprosencephaly is a congenital malformation that results from failure of the forebrain/prosencephalon to divide into right and left halves. Despite the literature on the genetic and chromosomal abnormalities associated with this condition, information on additional causes and explanations for variability in phenotypic expressivity are lacking. We report a case of early-onset intrauterine growth retardation with alobar holoprosencephaly, ethmocephaly, and hydronephrosis diagnosed on antenatal ultrasonography in a 27-year-old primigravida with no known risk factors or family history. The combination of holoprosencephaly with associated midline facial anomalies and the genitourinary abnormality, in this case, constitutes a rare phenotypic presentation. This case emphasizes the importance of antenatal ultrasonography in the early detection of lethal anomalies like alobar holoprosencephaly. The pregnancy was safely terminated in accordance with the mother's decision.
PubMed: 36046320
DOI: 10.7759/cureus.27375 -
Journal of Pediatric Neurosciences 2016
PubMed: 27195049
DOI: 10.4103/1817-1745.181262 -
Middle East African Journal of... Oct 2012Ethmocephaly is the rarest form of holoprosencephaly, which occurs due to an incomplete cleavage of the forebrain. Clinically, the disease presents with a proboscis,...
Ethmocephaly is the rarest form of holoprosencephaly, which occurs due to an incomplete cleavage of the forebrain. Clinically, the disease presents with a proboscis, hypotelorism, microphthalmos and malformed ears. Amniotic band syndrome is another rare congenital malformation with ring-like constriction bands in the limbs, head, face or trunk. We present a case of ethmocephaly with amniotic band syndrome, which is likely the first of its kind, published in the literature.
Topics: Abnormalities, Multiple; Amniotic Band Syndrome; Fatal Outcome; Holoprosencephaly; Humans; Infant, Newborn; Male; Tomography, X-Ray Computed; Torso
PubMed: 23248551
DOI: 10.4103/0974-9233.102769 -
Journal of Medical Genetics Dec 1991Craniofacial skeletal development in eight human holoprosencephalic fetuses from second trimester abortions were examined by radiography and histology. The whole...
Craniofacial skeletal development in eight human holoprosencephalic fetuses from second trimester abortions were examined by radiography and histology. The whole spectrum of associated facial malformations from anophthalmia through cyclopia, ethmocephaly, cebocephaly, and median cleft lip to short philtrum was represented. Cases with the most severe facial malformations also had the most severely affected facial skeleton. In the facial skeleton, the premaxilla was most often affected; it was absent in seven cases and malformed in the one with only a short philtrum. This and other facial skeletal malformations can be explained as abnormal fusion of the facial bones because of defective development of the nasal cartilage. The occipital bones were normal, but the basicranial skeleton anterior to the spheno-occipital junction was affected in all cases. The findings support the hypothesis that the facial malformations in holoprosencephaly result from disturbance in embryonal life of the mesoderm at the rostral end of the notochord.
Topics: Facial Bones; Fetus; Gestational Age; Holoprosencephaly; Humans; Radiography; Skull
PubMed: 1757961
DOI: 10.1136/jmg.28.12.846