The development of the mammalian cerebellum is orchestrated by both cell-autonomous programs and inductive environmental influences. Here, we describe the main processes of cerebellar ontogenesis, highlighting the neurogenic strategies used by developing progenitors, the genetic programs involved in cell fate specification, the progressive changes of structural organization, and some of the better-known abnormalities associated with developmental disorders of the cerebellum.

/pdf/consensus-paper-cerebellar-development-if424wuguo.pdf

Consensus Paper: Cerebellar Development.

https://www.reed.edu/biology/courses/BIO431S05_2015/primary/konopka_etal_2012.pdf

Human-Specific Transcriptional Networks in the Brain

Walker-Warburg syndrome (WWS) is clinically defined as congenital muscular dystrophy that is accompanied by a variety of brain and eye malformations. It represents the most severe clinical phenotype in a spectrum of diseases associated with abnormal post-translational processing of a-dystroglycan that share a defect in laminin-binding glycan synthesis1. Although mutations in six genes have been identified as causes of WWS, only half of all individuals with the disease can currently be diagnosed on this basis2. A cell fusion complementation assay in fibroblasts from undiagnosed individuals with WWS was used to identify five new complementation groups. Further evaluation of one group by linkage analysis and targeted sequencing identified recessive mutations in the ISPD gene (encoding isoprenoid synthase domain containing). The pathogenicity of the identified ISPD mutations was shown by complementation of fibroblasts with wild-type ISPD. Finally, we show that recessive mutations in ISPD abolish the initial step in laminin-binding glycan synthesis by disrupting dystroglycan O-mannosylation. This establishes a new mechanism for WWS pathophysiology.

http://www.physiology.uiowa.edu/campbell/Events/426Willer.pdf

ISPD loss-of-function mutations disrupt dystroglycan O-mannosylation and cause Walker-Warburg syndrome

Congenital muscular dystrophies are a group of rare neuromuscular disorders with a wide spectrum of clinical phenotypes. Recent advances in understanding the molecular pathogenesis of congenital muscular dystrophy have enabled better diagnosis. However, medical care for patients with congenital muscular dystrophy remains very diverse. Advances in many areas of medical technology have not been adopted in clinical practice. The International Standard of Care Committee for Congenital Muscular Dystrophy was established to identify current care issues, review literature for evidence-based practice, and achieve consensus on care recommendations in 7 areas: diagnosis, neurology, pulmonology, orthopedics/rehabilitation, gastroenterology/ nutrition/speech/oral care, cardiology, and palliative care. To achieve consensus on the care recommendations, 2 separate online surveys were conducted to poll opinions from experts in the field and from congenital muscular dystrophy families. The final consensus was achieved in a 3-day workshop conducted in Brussels, Belgium, in November 2009. This consensus statement describes the care recommendations from this committee.

/pdf/consensus-statement-on-standard-of-care-for-congenital-46zlca260o.pdf

Consensus Statement on Standard of Care for Congenital Muscular Dystrophies

Cerebellar hypoplasia (CH) refers to a cerebellum with a reduced volume, and is a common, but non-specific neuroimaging finding. The etiological spectrum of CH is wide and includes both primary (malformative) and secondary (disruptive) conditions. Primary conditions include chromosomal aberrations (e.g., trisomy 13 and 18), metabolic disorders (e.g., molybdenum cofactor deficiency, Smith-Lemli-Opitz syndrome, and adenylosuccinase deficiency), genetic syndromes (e.g., Ritscher-Schinzel, Joubert, and CHARGE syndromes), and brain malformations (primary posterior fossa malformations e.g., Dandy-Walker malformation, pontine tegmental cap dysplasia and rhombencephalosynapsis, or global brain malformations such as tubulinopathies and α-dystroglycanopathies). Secondary (disruptive) conditions include prenatal infections (e.g., cytomegalovirus), exposure to teratogens, and extreme prematurity. The distinction between malformations and disruptions is important for pathogenesis and genetic counseling. Neuroimaging provides key information to categorize CH based on the pattern of involvement: unilateral CH, CH with mainly vermis involvement, global CH with involvement of both vermis and hemispheres, and pontocerebellar hypoplasia. The category of CH, associated neuroimaging findings and clinical features may suggest a specific disorder or help plan further investigations and interpret their results. Over the past decade, advances in neuroimaging and genetic testing have greatly improved clinical diagnosis, diagnostic testing, recurrence risk counseling, and information about prognosis for patients and their families. In the next decade, these advances will be translated into deeper understanding of these disorders and more specific treatments.

Cerebellar hypoplasia: differential diagnosis and diagnostic approach.

A full-term male neonate born of a non-consanguineous marriage presented to us on the first day of life with large head (figure 1) and generalised hypotonia. He had microphthalmia and white reflex in pupillary areas. There was a family history of three neonatal deaths, the parents did not recall any of these babies having had large head.



Figure 1 
Large head.



His creatine kinase (CK) level was very high …

https://casereports.bmj.com/content/casereports/2011/bcr.04.2011.4102.full.pdf

Walker–Warburg syndrome

A 3-day-old, full-term male neonate born by a caearean section for obstructed labour presented with respiratory distress beginning within hours of birth. There was no history of prolonged rupture of membranes or maternal fever.

The baby cried immediately after birth and there was no need for resuscitation.

Antenatal sonography done at the referring centre had detected some abnormality in the posterior cranial …

Dandy-Walker malformation.

During the 3rd week of intrauterine life there is a communication between the intraembryonic gut and the yolk sac. As the development proceeds this communication narrows into a tube known as the vitellointestinal duct (VID). With the establishment of placental nutrition this duct usually becomes obliterated by the end of the 7th week of intrauterine life. In about 2% of humans this duct persists and gives rise to a group of anomalies of which Meckel's diverticulum is the commonest and complete patency of the duct is the rarest.1 We report a case of a 4-month-old infant who presented with umbilical polyp, discharge from the umbilicus, significant dehydration and failure to thrive because of complete patency of the VID.

/pdf/patent-vitellointestinal-duct-2wqhpglugj.pdf

Patent vitellointestinal duct.

A 5-year-old girl presented with abdominal pain, intermittent jaundice and a gall bladder lump. Clinical examination and preoperative imaging suggested the diagnosis of a type I choledochal cyst (CDC). During surgery, this was found to be a hydatid cyst (HC) occupying the head of pancreas causing obstruction to the common bile duct (CBD). A pancreatic HC mimicking a CDC and presenting with CBD obstruction is unusual.

/pdf/hydatid-cyst-of-head-of-pancreas-mimicking-choledochal-cyst-4ys7jqvuk9.pdf

Hydatid cyst of head of pancreas mimicking choledochal cyst.

Neuroregression in infants has varied aetiology and vitamin B12 deficiency is one of the uncommon causes. Infantile vitamin B12 deficiency is encountered in malnourished infants or in offspring of strict vegan mothers. We present two cases, both infants of 10 and 8 months of age, whose mothers had vitamin B12 deficiency. On admission, the patients were apathic, hypotonic and lethargic. Serum vitamin B12 levels were below normal limits. On cranial MRI, T2-weighted images revealed frontoparietal cortical atrophy. Both the infants responded to vitamin B12 treatment.

Sanwar Agrawal

Papers

Walker–Warburg syndrome

Dandy-Walker malformation.

Patent vitellointestinal duct.

Hydatid cyst of head of pancreas mimicking choledochal cyst.

Neuro-regression in vitamin B12 deficiency.