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International Journal of Surgery Case... Apr 2022Holoprosencephaly is a rare brain malformation consisting of impaired midline cleavage of the embryonic forebrain presenting with variable features of craniofacial...
INTRODUCTION AND IMPORTANCE
Holoprosencephaly is a rare brain malformation consisting of impaired midline cleavage of the embryonic forebrain presenting with variable features of craniofacial dysmorphism. It affects 1 in 10,000 live births occurring more in females than males. We present a case of alobar HPE and aim to raise awareness on the importance of early prenatal detection and counselling.
CASE PRESENTATION
We present a case of 3200-gram female baby, born by spontaneous vaginal delivery with APGAR scores of 5 and 6 in the first and fifth minute of life respectively. On admission, the baby was lethargic, had central and peripheral cyanosis, hypothermic with temperature of 32.1 °C, respiratory rate of 65 breaths/min, heart rate of 135 beats/min and oxygen saturation of 94% with an oropharyngeal airway and on oxygen support via a face mask. She had microcephaly, hypotelorism, and a small nose with a single imperforate nostril. She was diagnosed to have alobar holoprosencephaly with cebocephaly. A computed tomography scan of the brain revealed a cephalohematoma in the vertex and an intranasal soft tissue density lesion blocking the entrance measuring approximately 10 × 8.5 mm. Absence of the corpus callosum and septum pellucidum with a resulting monoventricle formed from the lateral ventricles, the fusion of the thalami and a sizeable arachnoid cyst involving the left cerebellar hemisphere were evident. She was started on IV antibiotics and IV fluids. Non-invasive airway management was opted for by the ENT team based on the condition of the baby. She succumbed to death 6 days post admission due to severe respiratory failure.
CLINICAL DISCUSSION
The types of HPE are alobar, semi lobar, lobar and interhemispheric variants. Alobar HPE is the most severe form and is incompatible with life. Clinical presentation entails facial dysmorphism with features of hypotelorism, microcephaly and a blind ended nostril. Alobar and semilobar HPE can reliably be diagnosed with ultrasound during the first and second trimesters of pregnancy. Absence of choroid plexus and fused cortex are pathognomonic characteristic on ultrasound and CT scan respectively.
CONCLUSION
Alobar holoprosencephaly is a rare brain malformation which is incompatible with life. Prenatal ultrasound screening of the foetus brain is essential and reliable in making a diagnosis. Absence of the "butterfly" sign in the foetal brain ultrasonography should raise a high index of suspicion for brain malformation with unfavourable outcome. Legal medical termination of pregnancy may serve as an early intervention.
PubMed: 35364389
DOI: 10.1016/j.ijscr.2022.106960 -
Taiwanese Journal of Obstetrics &... Dec 2012Coexistence of Klinefelter syndrome and holoprosencephaly (HPE) is rare. We report alobar HPE, cebocephaly, and micropenis in a Klinefelter fetus of a mother with type 2...
OBJECTIVE
Coexistence of Klinefelter syndrome and holoprosencephaly (HPE) is rare. We report alobar HPE, cebocephaly, and micropenis in a Klinefelter fetus of a mother with type 2 diabetes mellitus with obesity and poor metabolic control.
CASE REPORT
A 38-year-old woman was referred for therapy of type 2 diabetes mellitus with poor glycemic control at 24 weeks of gestation. On examination, she had a body height of 162 cm and a body weight of 105 kg. She had been treated with oral medication for diabetes mellitus for 4 years with poor maternal metabolic control. She had prominent glucosuria and glycemia. Her hemoglobin A1c was 7.5% (normal range: 3.4-6.1%), and the fasting glucose level was 141 mg/mL (normal range: 70-99 mg/mL) during this visit. Her husband was 46 years old. Prenatal ultrasound revealed a singleton fetus with fetal biometry equivalent to 24 weeks, alobar HPE, cebocephaly, and micropenis. As a result of poor maternal heath and fetal anomaly, the parents elected to terminate the pregnancy, and a 986-g male fetus was delivered with hypotelorism, HPE, cebocephaly, micropenis, and cryptorchidism. Cytogenetic analysis of the cord blood revealed a karyotype of 47,XXY. The parental karyotypes were normal. Polymorphic DNA analysis revealed a paternal origin of the extra X chromosome. Molecular analysis of the HPE genes of SHH, ZIC2, SIX3, and TGIF revealed no mutations.
CONCLUSION
Prenatal diagnosis of HPE should include a biochemical examination to identify metabolic factors such as maternal diabetes, and preventive management should be considered in subsequent pregnancies to achieve good control of maternal diabetes.
Topics: Abnormalities, Multiple; Abortion, Eugenic; Adult; Diabetes Mellitus, Type 2; Female; Fetal Diseases; Holoprosencephaly; Humans; Karyotype; Klinefelter Syndrome; Male; Obesity; Pregnancy; Pregnancy in Diabetics; Prenatal Diagnosis
PubMed: 23276570
DOI: 10.1016/j.tjog.2012.09.021 -
Journal of Medical Case Reports Jul 2018The term holoprosencephaly was proposed by DeMyer and Zeman. It is a developmental defect of the embryonic forebrain with heterogeneous etiology including genetic and...
BACKGROUND
The term holoprosencephaly was proposed by DeMyer and Zeman. It is a developmental defect of the embryonic forebrain with heterogeneous etiology including genetic and environmental factors. It is commonly associated with midfacial defects and has a spectrum of presentations. There are four types: alobar, semilobar, lobar, and variant. Holoprosencephaly is relatively rare. The overall prevalence in a multicenter study was 1 in 13,000 to 18,000 live births. However, the presentation of holoprosencephaly with cebocephaly, micropenis, agenesis of middle phalanges of the fifth finger, and postaxial polydactyly in association with early onset preeclampsia is extremely rare. We report a case with a constellation of the above congenital anomalies.
CASE PRESENTATION
A 34-year-old gravida II para l woman presented to Felege Hiwot Referral Hospital with the diagnosis of semilobar holoprosencephaly and early onset preeclampsia with severity features. The gestational age at admission was 26 + 3 weeks. She is Amhara by ethnicity. The pregnancy was from a non-consanguineous marriage. She presented with the complaints of severe and persistent headache associated with blurring of vision and generalized body swelling. After she was stabilized, she and her husband were counselled and termination was decided. She gave birth after three doses of 100 microgram misoprostol given vaginally every 3 hours. The outcome was 1.1 kg male neonate; there were associated dysmorphic features of holoprosencephaly such as cebocephaly, micropenis, and postaxial polydactyl with agenesis of middle phalanges of the fifth finger. Only basic care was given and the neonate died after 20 minutes' stay in our neonatal intensive care unit. The mother was counselled to have preconception and antenatal screening in her next pregnancy. She left the hospital relatively well.
CONCLUSION
In women with a history of holoprosencephaly or holoprosencephaly in the current pregnancy, antenatal workups should include workup for fetal chromosomal disorders and metabolic workup for maternal preeclampsia. Sonographic diagnoses of holoprosencephaly always need a careful search for other congenital anomalies. In the severe forms, early termination should be counseled for its poor prognosis. Associated severe congenital anomalies and severe morbidities of the survivor can be discussed while counselling.
Topics: Abnormalities, Multiple; Adult; Female; Holoprosencephaly; Humans; Infant, Newborn; Male; Pre-Eclampsia; Pregnancy
PubMed: 29980223
DOI: 10.1186/s13256-018-1647-6 -
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 -
Annals of Medicine and Surgery (2012) Feb 2023Holoprosencephaly is a rare and possibly fatal neural tube defect represented by complete or partial forebrain noncleavage. It can be classified into four types: alobar,...
UNLABELLED
Holoprosencephaly is a rare and possibly fatal neural tube defect represented by complete or partial forebrain noncleavage. It can be classified into four types: alobar, semilobar, lobar, and middle interhemispheric fusion variant. It is usually diagnosed through prenatal ultrasound or after birth by visually observing the morphological abnormalities and/or through neurological screening. Potential causes include maternal diabetes, alcoholism, infections during pregnancy, drugs, and genetic causes.
CASE PRESENTATION
Herein, we report two cases of holoprosencephaly's rarest manifestations, albeit cebocephaly in the first case, and cyclopia with a probocis in the second. Cebocephaly, (hypotelorism with a single nostril and a blind-ended nose) was present in the first case; a Syrian newborn girl for a 41-year-old mother who works in collecting , and cyclopia with skull vault absence and posterior encephalocele in the second case; a Syrian newborn girl for a 26-year-old mother, the parents here where second-degree relatives.
CONCLUSIONS
Early diagnosis through ultrasound is preferred in such cases and management options should be assessed and discussed with the parents due to poor prognosis. Adherence to pregnancy follow-up programs is essential to detect malformations and disorders as early as possible, especially when risk factors exist. Also, this paper may suggest a potential correlation between and holoprosencephaly. Therefore, we suggest that more research should be done.
PubMed: 36845789
DOI: 10.1097/MS9.0000000000000176 -
Ear, Nose, & Throat Journal 2013We report a case of alobar holoprosencephaly (HPE) and cebocephaly associated with uncontrolled maternal type 1 (insulin-dependent) diabetes mellitus. Alobar HPE is the...
We report a case of alobar holoprosencephaly (HPE) and cebocephaly associated with uncontrolled maternal type 1 (insulin-dependent) diabetes mellitus. Alobar HPE is the most severe form of HPE. Patients with cebocephaly have ocular hypotelorism and a proboscis with a single, blind-ended nostril. Shortly after our patient was born, we were consulted for airway management, as the parents' goal was to bring their child home. A tracheostomy tube was placed, and choanal atresia repair was eventually performed. The infant was never decannulated, however, and she died at the age of 9 months of acute respiratory distress syndrome secondary to an upper respiratory infection. To the best of our knowledge, this case represents the longest reported survival of an infant with alobar HPE and cebocephaly. Decisions regarding the care of these infants should be made in a collaborative, multidisciplinary fashion, with special attention paid to the primary caregivers' goals of care.
Topics: Abnormalities, Multiple; Airway Management; Diabetes Mellitus, Type 1; Fatal Outcome; Female; Holoprosencephaly; Humans; Infant, Newborn; Pregnancy; Pregnancy in Diabetics
PubMed: 23599105
DOI: 10.1177/014556131309200416 -
Journal of Medical Genetics Sep 1997We report on the prenatal diagnosis of a case of cebocephaly, alobar holoprosencephaly, and microcephaly associated with a de novo proximal interstitial deletion of the... (Review)
Review
We report on the prenatal diagnosis of a case of cebocephaly, alobar holoprosencephaly, and microcephaly associated with a de novo proximal interstitial deletion of the long arm of chromosome 14: del(14)(q13q21.1) or (q13q21.2). This is the third case of holoprosencephaly in association with a deletion in this region. The present report concerns the association between prenatal craniofacial development, a holoprosencephaly locus, and the chromosomal segment 14q13.
Topics: Abnormalities, Multiple; Adult; Brain; Chromosomes, Human, Pair 14; Female; Gene Deletion; Humans; Male; Microcephaly; Pregnancy; Pregnancy Trimester, Second; Prenatal Diagnosis; Ultrasonography
PubMed: 9321769
DOI: 10.1136/jmg.34.9.777 -
Scientific Reports Jan 2019This paper is part of the emerging field of Evolutionary Developmental Pathology, dedicated to study the links between normal and abnormal development, evolution and...
This paper is part of the emerging field of Evolutionary Developmental Pathology, dedicated to study the links between normal and abnormal development, evolution and human pathologies. We analyzed the head musculoskeletal system of several 'natural mutant' newborn lambs displaying various degrees of abnormality, from mild defects to cebocephaly and to cyclopia, and compared them with humans. Interestingly, muscle defects are less marked than osteological ones, and contrarily to the latter they tend to display left-right assymetries. In individuals with cebocephalic and even cyclopic skulls almost all head muscles are normal. The very few exceptions are some extraocular muscles and facial muscles that normally attach to osteological structures that are missing in the abnormal heads: such muscles are instead attached to the 'nearest topological neighbor' of the missing osteological structure, a pattern also found in cyclopic humans. These observations support Alberch's ill-named "logic of monsters" - as a byproduct of strong developmental/topological constraints anatomical patterns tend to repeat themselves, even severe malformations displayed by distantly related taxa. They also support the idea that mammalian facial muscles reverted to an ancestral 'nearest-neighbor' muscle-bone type of attachment seen in non-vertebrate animals and in vertebrate limbs, but not in other vertebrate head muscles.
Topics: Animals; Animals, Newborn; Biological Evolution; Head; Holoprosencephaly; Humans; Infant, Newborn; Musculoskeletal Abnormalities; Principal Component Analysis; Sheep, Domestic
PubMed: 30700788
DOI: 10.1038/s41598-018-37735-9 -
Case Reports in Otolaryngology 2021Holoprosencephaly (HPE) is a rare cerebrofacial abnormality resulting from the complete or partial failure of the diverticulation and cleavage of the primitive...
BACKGROUND
Holoprosencephaly (HPE) is a rare cerebrofacial abnormality resulting from the complete or partial failure of the diverticulation and cleavage of the primitive forebrain. It has an incidence at birth of 1:16000. . We report a case of a 2600 g newborn female delivered by an HIV-infected mother in whom an antenatal ultrasound scan at 34 weeks' gestation reported features of fetal alobar holoprosencephaly. The neonate was born with cebocephaly, a monkey-like head, and did not survive for more than 30 minutes following delivery by caesarian section despite oxygen therapy.
CONCLUSION
Alobar HPE with cebocephaly remains incompatible with life. In this resource-limited setting, the diagnosis was made clinically, and only an ultrasound scan was performed to confirm the diagnosis. Chromosomal analysis could have given more information.
PubMed: 34733564
DOI: 10.1155/2021/7282283