Cranial vault reduction cranioplasty for severe macrocephaly due to holoprosencephaly and subdural hygroma: a case report.

BACKGROUND: Severe macrocephaly can still be found in developing countries. This condition is usually caused by neglected hydrocephalus and can cause a lot of morbidities. Cranial vault reconstruction cranioplasty is the main treatment option for severe macrocephaly. Holoprosencephaly is often seen with features of microcephaly. Hydrocephalus should be considered as the main cause in HPE patients with features of macrocephaly. In this report, we present a rare case of cranial vault reduction cranioplasty procedure in patient with severe macrocephaly due to holoprosencephaly and subdural hygroma. CASE DESCRIPTION: A 4-year-10-month-old Indonesian boy was admitted with head enlargement since birth. He had a history of VP shunt placement when he was 3 months old. But the condition was neglected. Preoperative head CT showed massive bilateral subdural hygroma that compressed brain parenchyma caudally. From the craniometric calculation, the occipital frontal circumference was 70.5 cm with prominent vertex expansion, the distance between nasion to inion was 11.91 cm and the vertical height was 25.59 cm. The preoperative cranial volume was 24.611 cc. The patient underwent subdural hygroma evacuation and cranial vault reduction cranioplasty. The postoperative cranial volume was 10.468 cc. CONCLUSION: Subdural hygroma can be a rare cause of severe macrocephaly in holoprosencephaly patients. Cranial vault reduction cranioplasty and subdural hygroma evacuation is still the main treatment option. Our procedure successfully reduces significant cranial volume (57.46% volume reduction).

Sinus pericranii associated with syntelencephaly: a case report.

BACKGROUND: Sinus pericranii is a rare cranial venous malformation resulting in a subcutaneous mass due to abnormal communication between intracranial and subperiosteal/interperiosteal veins. To date, to the best of our knowledge, there are no reports of sinus pericranii associated with syntelencephaly, a subtype of lobar holoprosencephaly. We herein report a case of sinus pericranii associated with syntelencephaly. This report can provide us better understanding of the etiology of sinus pericranii, the potential risks, and the treatment options for these patients. CASE PRESENTATION: A 2-year-4-month old female patient who received the diagnosis of syntelencephaly as a neonate presented with a subcutaneous mass in the parietal region. The mass was soft, nonpulsatile, 3 × 2 cm in size, and showed enlargement in the lying position. Color cranial Doppler ultrasound, head magnetic resonance imaging (MRI), and cerebral angiography revealed a dilated vessel passing through the parietal bone and forming a communication between the superior sagittal sinus and scalp veins. Based on these findings, sinus pericranii was diagnosed. The head MRI also showed coronal craniosynostosis, a tight posterior fossa. At age 2 years and 7 months, the patient underwent a transection of the sinus pericranii and the mass resolved without any complications or recurrences for more than 2.5 years to date. CONCLUSION: Sinus pericranii is a rare cranial and venous malformation sometimes accompanied by brain malformations or craniosynostosis that may become more apparent as the brain and skull develop. Since this condition can be complicated by intracranial hemorrhage and sinus thrombosis, early detection is necessary to determine the treatment options. Physicians should be alert to the possibility of this condition if they observe a soft cranial mass that appears to decrease in size in the sitting position and bulge in the lying position.

The solitary median maxillary central incisor (SMMCI) syndrome: Associations, prenatal diagnosis, and outcomes.

Solitary median maxillary central incisor (SMMCI) syndrome is a complex disorder consisting of multiple, developmental defects involving midline structures of the head, which includes the cranial bones, the maxilla, and its container dentition (specifically the central incisor tooth germ), together with other midline structures of the body. SMMCI may appear as an isolated trait or in association with other midline developmental anomalies. We describe the case of a patient with SMMCI. He presented with a solitary median maxillary incisor, short stature, corpus callosum anomalies and a microform of holoprosencephaly (HPE), diabetes insipidus, and neurodevelopmental delay. The diagnosis was performed postnatally based on clinical features, radiological imaging, and a comprehensive genetic study. SMMCI can be diagnosed during the prenatal or neonatal periods or during infancy. Evaluation of the superior maxillary bone is important for prenatal diagnosis. Direct evaluation through bidimensional ultrasound or the use of multiplanar ultrasound or tridimensional reconstruction should be performed in cases of brain or face malformations. Early diagnosis can contribute to improved prenatal assessment and postnatal management.

First-Trimester Diagnosis of Agnathia-Otocephaly Complex: A Series of 4 Cases and Review of the Literature.

First-trimester ultrasound findings in 4 fetuses with agnathia-otocephaly complex are described. In addition, information from 3 cases reported in the literature was also reviewed, for a total of 7 cases analyzed. All 7 fetuses presented with agnathia and 6 with ventrocaudal displacement of the ears (melotia/synotia). Four fetuses had holoprosencephaly. In 6 cases, the parents opted for termination of pregnancy. The remaining case resulted in premature delivery at 26 weeks due to severe polyhydramnios and early neonatal death. This report highlights the important role of ultrasound in the identification of agnathia-otocephaly complex in the first trimester of pregnancy.

Reverse Distraction for Treatment of Hydrocephalic Macrocephaly in Late Childhood.

Macrocephaly diminishes quality of life for children whose head size inhibits independent mobility and appropriate interaction with caregivers. Cranial reduction is a method of addressing these issues, historically with a high morbidity due most commonly to bleeding and shunt complications. The authors present a 9-year-old girl with holoprosencephaly and severe macrocephaly from progressive hydrocephalus who underwent cranial reduction via reverse distraction osteogenesis, a method to slowly reduce the skull volume. The patient underwent circumferential occipital temporoparietal frontal craniotomy with placement of 4 cranial distractors, followed approximately 1 month later by removal of the distractors and cranioplasty with resorbable fixation devices. The patient demonstrated significant postoperative improvement in head control and interaction in school activities. This is the oldest patient with macrocephaly treated with reverse distraction in the literature to date. The slow contraction of the cranial vault with limited bony surgery at the time of initial reduction provides an additional safety margin, and should be considered in older children presenting with profound macrocephaly.

Management Strategies for Hydrocephalus in Alobar Holoprosencephaly: A Case Report and Discussion.

Holoprosencephaly is a rare congenital malformation resulting from an impaired midline division of the prosencephalon into distinct cerebral hemispheres. Hydrocephalus is a frequent problem among the few survivors with alobar holoprosencephaly (aHPE), its most severe form. The literature about neurosurgical management of hydrocephalus in this condition is limited and dispersed, and there are still some points that need to be resolved. We report the case of a newborn with aHPE, hydrocephalus, and central diabetes insipidus. We delineate the complexity of the management of these patients and emphasize the benefits of using an initial programmable shunt valve. Further discussion about management strategies includes reviewing previous reports and the benefits of shunting for hypothalamic osmoreceptor function.

Human germline hedgehog pathway mutations predispose to fatty liver.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease. Activation of hedgehog (Hh) signaling has been implicated in the progression of NAFLD and proposed as a therapeutic target; however, the effects of Hh signaling inhibition have not been studied in humans with germline mutations that affect this pathway. METHODS: Patients with holoprosencephaly (HPE), a disorder associated with germline mutations disrupting Sonic hedgehog (SHH) signaling, were clinically evaluated for NAFLD. A combined mouse model of Hh signaling attenuation (Gli2 heterozygous null: Gli2+/-) and diet-induced NAFLD was used to examine aspects of NAFLD and hepatic gene expression profiles, including molecular markers of hepatic fibrosis and inflammation. RESULTS: Patients with HPE had a higher prevalence of liver steatosis compared to the general population, independent of obesity. Exposure of Gli2+/- mice to fatty liver-inducing diets resulted in increased liver steatosis compared to wild-type mice. Similar to humans, this effect was independent of obesity in the mutant mice and was associated with decreased expression of pro-fibrotic and pro-inflammatory genes, and increased expression of PPARγ, a potent anti-fibrogenic and anti-inflammatory regulator. Interestingly, tumor suppressors p53 and p16INK4 were found to be downregulated in the Gli2+/- mice exposed to a high-fat diet. CONCLUSIONS: Our results indicate that germline mutations disrupting Hh signaling promotes liver steatosis, independent of obesity, with reduced fibrosis. While Hh signaling inhibition has been associated with a better NAFLD prognosis, further studies are required to evaluate the long-term effects of mutations affecting this pathway. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is characterized by excess fat deposition in the liver predominantly due to high calorie intake and a sedentary lifestyle. NAFLD progression is usually accompanied by activation of the Sonic hedgehog (SHH) pathway leading to fibrous buildup (scar tissue) and inflammation of the liver tissue. For the first time patients with holoprosencephaly, a disease caused by SHH signaling mutations, are shown to have increased liver steatosis independent of obesity. This observation was recapitulated in a mouse model of attenuated SHH signaling that also showed increased liver steatosis but with decreased fibrosis and inflammation. While SHH inhibition is associated with a good NAFLD prognosis, this increase in liver fat accumulation in the context of SHH signaling inhibition must be studied prospectively to evaluate its long-term effects, especially in individuals with Western-type dietary habits.

Subcortical heterotopia appearing as huge midline mass in the newborn brain.

INTRODUCTION: We report the case of a 2-year-old boy who showed a huge midline mass in the brain at prenatal assessment. CASE REPORT: After birth, magnetic resonance imaging (MRI) revealed a conglomerate mass with an infolded microgyrus at the midline, which was suspected as a midline brain-in-brain malformation. MRI also showed incomplete cleavage of his frontal cortex and thalamus, consistent with lobar holoprosencephaly. The patient underwent an incisional biopsy of the mass on the second day of life. The mass consisted of normal central nervous tissue with gray and white matter, representing a heterotopic brain. The malformation was considered to be a subcortical heterotopia. With maturity, focal signal changes and decreased cerebral perfusion became clear on brain imaging, suggesting secondary glial degeneration. Coincident with these MRI abnormalities, the child developed psychomotor retardation and severe epilepsy focused on the side of the intracranial mass.

Primary Abbe Flap for Median Cleft Lip Deformity: New Trends on an Old Concept.

OBJECTIVE: The authors present our experience using primary Abbe flaps for median cleft lip. METHODS: The records of 9 patients who underwent primary Abbe flaps were reviewed for indications, operative details, and complications. Flap design is discussed, including the "W" method to facilitate columellar reconstruction. Maxillomandibular fixation was not used. RESULTS: From 2004 to 2015, 9 patients with median cleft lip received primary Abbe flaps. Mean age was 10.2 ± 6.2 months. Lobar holoprosencephaly was confirmed by imaging in 5 of the 9 patients. Operative time averaged 70 ± 22 minutes. Flap division was performed at a mean of 3.6 ± 0.9 weeks. Patients were followed for a mean of 45 ± 49 months. No flaps were lost to vascular compromise and no dehiscences or infections were noted after initial repair. Five patients required prolonged intubation ranging from 4 to 7 days and 3 required transition to gastric feedings postoperatively. One patient with holoprosencephaly expired for reasons independent of surgery. Four patients have undergone 5 lip revisions to date. CONCLUSIONS: Patients with holoprosencephaly-spectrum disorder and median cleft lip have more favorable prognoses today. The Abbe flap may be safely and advantageously used for the primary repair of median cleft lip with extreme prolabial tissue deficiency.

A Postsurgical Obturator After Cleft Lip Repair in Patients With Holoprosencephaly.

Several factors affect healing of lip repair in children with complete cleft lip and palate in the immediate postoperative period. However, children with holoprosencephaly present a unique challenge. Because of their wide midline clefts and premaxillary agenesis they have protrusive positioning of their tongue, which can adversely affect the surgical result. In these cases we have found a postsurgical obturator made with hard-setting acrylic to be especially useful. Such an appliance may be used for the initial healing period (1-2 weeks). Two cases are presented here where such a device was used successfully.

[Frequency of holoprosencephaly in Chile]. / ECLAMC: 41 años de vigilancia de la holoprosencefalia en Chile. Período 1972-2012.

BACKGROUND: Holoprosencephaly is a structural anomaly of the brain that consists in a defect of the prosencephalon development that leads to face and neurological defects of variable intensity. AIM: To estimate holoprosencephaly prevalence at birth. PATIENTS AND METHODS: All cases of holoprosencephaly, born alive or stillbirths, registered in the 15 Chilean Hospitals of the Latin American Collaborative Study of Congenital Malformations (ECLAMC) between 1972 and 2012, were studied. Craniofacial and other anomalies found in newborns affected by holoprosencephaly are described. RESULTS: Fifty five cases of holoprosencephaly (58% males) were found among the 798.222 registered births (rendering a prevalence at birth of 0.69 per 10.000 newborns). The most common cranial defect was medial cleft lip with cleft palate (27.3%), bilateral cleft lip (11%) or both (38.2%), cyclopia (14%), single nostril (10.9%) and proboscis (9.1%). Eleven percent cases had a trisomy 13. A slight increase in prevalence over time was observed. CONCLUSIONS: Holoprosencephaly has a low frequency in Chile and is associated to trisomy 13. The increase in prevalence could be explained by a better prenatal diagnosis (ultrasonography).

Second trimester ultrasound markers of fetal aneuploidy.

Although it is widely accepted that the best time to screen for chromosomal abnormalities is the first trimester, ultrasound evaluation of the fetus in the second trimester has also been shown to be useful for this purpose. A multitude of markers of varying strength has been developed over the past 30 years. In addition, the optimal time to diagnose fetal anomalies with confidence is also the mid second trimester. Therefore, performance of obstetrical ultrasound at this point in gestation continues to be an important component of prenatal care.

A novel association of an uncommon pigmentation pattern: coexistence of cutis tricolor with intracranial teratoma and holoprosencephaly.

Cutis tricolor was first described in a 17-year-old male patient by Happle et al. as a rare coexistence of circumscribed hyperpigmentation and hypopigmentation close to each other on a background of normally pigmented skin. Cutis tricolor has been reported as an isolated cutaneous finding or in various associations. To the best of our knowledge, cutis tricolor in association with teratoma and holoprosencephaly has not been reported in the literature. Herein, we report a male patient who presented with a teratoma and a combination of whorl-like hypopigmentation together with hyperpigmented patches adjacent to each other on intermediately pigmented skin. This case report supports the view that cutis tricolor may be a marker of an underlying neurological abnormality.

[Solitary median maxillary central incisor syndrome]. / Het solitaire mediane maxillaire centrale incisief-syndroom.

Solitary Median Maxillary Central Incisor syndrome is a rare condition (prevalence 1:50,000), with the characteristic dental feature of a solitary central incisor in the maxilla, positioned exactly in the midline. This single incisor is symmetrical and can be present in the deciduous as well as in the permanent dentition. The syndrome can occur as a mild form of the broad holoprosencephaly-spectrum, but can also be associated with other characteristics. The etiology is still largely unknown, but the syndrome is probably based especially on genetic causes. Early recognition of the syndrome is of great importance for establishing the diagnosis, for additional investigation, for possible treatment of associated anomalies and for the correct advice concerning the risk of inheritance of severe congenital birth defects, related to holoprosencephaly. Dentists and orthodontists can play an important role in this regard and should therefore be able to recognise the clinical features of this condition and know how to refer a patient for further diagnostic counselling.

Effects of GLP1 receptor analogues in obesity with neurodevelopmental disorder: case report of a patient with holoprosencephaly.

Holoprosencephaly is an anomaly in the division of the prosencephalon into cerebral hemispheres during the second month of gestation. Patients can present with early-onset obesity favoured by the cognitive impairment. We present a case of a 24 year-old woman with holoprosencephaly and class III obesity who was treated by 2.4 mg/week SEMAGLUTIDE. Her body weight decreased from 115.3 to 94.3 kg after one-year (18% of total body weight loss). In addition, she presented a marked reduction in self- and hetero-aggressive behaviour when exposed to the sight of food. The treatment was well tolerated, with the exception of a few vomiting when eating palatable food too quickly. GLP1-RAs may be interesting for obesity treatment in the context of neurodevelopmental disorders. They appear to reduce compulsive eating and aggressive behaviour, particularly in relation to exposure to food, and lead to weight loss similar to that seen in people without neurodevelopmental disorders.

Dual white matter pathology in fetal holoprosencephaly featuring concurrent malformative and destructive features: A case series.

Holoprosencephaly (HPE) is a classic brain malformation involving defective forebrain induction and patterning. Cases of HPE bearing white matter abnormalities have not been well documented, with only rare cases exhibiting hypoxic-ischemic damage. However, neuroradiologic studies of HPE using diffusion tensor imaging have suggested the presence of white matter architectural disarray. Described in this case series are the clinicopathologic features of 8 fetuses with HPE who underwent autopsy at BC Children's Hospital. All 8 cases exhibited subacute to chronic, periventricular leukomalacia (PVL)-like white matter pathology, with 7 of 8 cases also demonstrating aberrant white matter tracts, one of which manifested as a discreet bundle crossing the midline within the ventral aspects of the fused deep gray nuclei. In 6 of these 7 cases, the PVL-like pathology resided within this aberrant white matter tract. Original workup, alongside an additional HPE-focused next-generation sequencing panel identified a likely etiologic cause for the HPE in 4 cases, with an additional 2 cases exhibiting a variant of unknown significance in genes previously suggested to be involved in HPE. Despite our in-depth clinicopathologic and molecular review, no unifying etiology was definitively identified among our series of fetal HPE bearing this unusual pattern of white matter pathology.