Genes disrupted in human microcephaly (meaning "small brain") define key regulators of neural progenitor proliferation and cell-fate specification. In comparison, genes mutated in human lissencephaly (lissos means smooth and cephalos means brain) highlight critical regulators of neuronal migration. Here, we report two families with extreme microcephaly and grossly simplified cortical gyral structure, a condition referred to as microlissencephaly, and show that they carry homozygous frameshift mutations in NDE1, which encodes a multidomain protein that localizes to the centrosome and mitotic spindle poles. Both human mutations in NDE1 truncate the C-terminal NDE1domains, which are essential for interactions with cytoplasmic dynein and thus for regulation of cytoskeletal dynamics in mitosis and for cell-cycle-dependent phosphorylation of NDE1 by Cdk1. We show that the patient NDE1 proteins are unstable, cannot bind cytoplasmic dynein, and do not localize properly to the centrosome. Additionally, we show that CDK1 phosphorylation at T246, which is within the C-terminal region disrupted by the mutations, is required for cell-cycle progression from the G2 to the M phase. The role of NDE1 in cell-cycle progression probably contributes to the profound neuronal proliferation defects evident in Nde1-null mice and patients with NDE1 mutations, demonstrating the essential role of NDE1 in human cerebral cortical neurogenesis.

Iron deficiency anemia is extremely common, particularly in the developing world, reaching a state of global epidemic. Iron deficiency during pregnancy is one of the leading causes of anemia in infants and young children. Many women go through the entire pregnancy without attaining the minimum required intake of iron. This review aims to determine the impact of maternal iron deficiency and iron deficiency anemia on infants and young children. Extensive literature review revealed that iron deficiency is a global nutritional problem affecting up to 52% of pregnant women. Many of these women are symptomatic. Lack of proper weight gain during pregnancy is an important predictor of iron deficiency.

Cerebral palsy (CP) is a common pediatric disorder occurring in about 2 to 2.5 per 1000 live births. It is a chronic motor disorder resulting from a non-progressive (static) insult to the developing brain. CP is the clinical presentation of a wide variety of cerebral cortical or sub-cortical insults occurring during the first year of life. The commonest cause of CP remains unknown in 50% of the cases; prematurity remains the commonest risk factor. Children with CP suffer from multiple problems and potential disabilities such as mental retardation, epilepsy, feeding difficulties, and ophthalmologic and hearing impairments. Screening for these conditions should be part of the initial assessment. The child with CP is best cared for with an individualized treatment plan that provides a combination of interventions. This requires the provision of a number of family-centered services that make a difference in the lives of these children and their families. Management of spasticity can be challenging with a wide variety of possible therapeutic interventions. The treatment must be goal oriented, such as to assist with mobility, reduce or prevent contractures, improve positioning and hygiene, and provide comfort. Each member of the child’s multidisciplinary team, including the child and both parents, should participate in the serial evaluations and treatment planning.

Cerebral palsy (CP) is a common chronic motor disorder with associated cognitive, communicative, and seizure disorders. Children with CP have a higher risk of dental problems creating significant morbidity that can further affect their wellbeing and negatively impact their quality of life. Screening for dental disease should be part of the initial assessment of any child with CP. The objective of this article is to present an updated overview of dental health issues in children with CP and outline important preventative and practical strategies to the management of this common comorbidity. Providing adequate oral care requires adaptation of special dental skills to help families manage the ongoing health issues that may arise. As oral health is increasingly recognized as a foundation for general wellbeing, caregivers for CP patients should be considered an important component of the oral health team and must become knowledgeable and competent in home oral health practices.

Osteomalacia is an uncommon cause of muscle weakness [1][2][3] . However, myopathy is relatively common in osteomalacia and may be the initial feature in up to 30% of patients 4 . Vitamin D deficiency is the most common cause of osteomalacia. Vitamin D3 (cholecalciferol) is synthesized nonenzymatically in the skin from 7-dehydrocholesterol during exposure to ultraviolet rays in sunlight. Vitamin D deficiency can be caused by unusually low ABSTRACT: Background: Osteomalacia is an uncommon cause of muscle weakness. Our objectives were to describe features of myopathy associated with Vitamin D deficiency and examine the contributing factors leading to osteomalacic myopathy in our region. Methods: Patients identified retrospectively for the six year period ending in December 2006 with the diagnosis of osteomalacia and/or Vitamin D deficiency associated proximal muscle weakness were included. They were followed in three major centers in western Saudi Arabia. Clinical, biochemical, radiological, and electrophysiological findings were collected before and after Vitamin D treatment by chart review. Results: Forty seven female patients aged 13-46 years (mean 23.5, SD 4.5) were included. All were veiled and covered heavily when outside the house for social and cultural reasons. Only eight (17%) had adequate varied diet with daily milk ingestion. All patients presented with progressive proximal muscle weakness lasting 6-24 months (mean 14) prior to our evaluation. The weakness was severe in six (13%) patients leading to wheel chair bound states. Associated musculoskeletal pain involving the back, hips, or lower limbs was common (66%). Osteomalcia was the referral diagnosis in only 11 patients and the remaining 36 (77%) patients were misdiagnosed. All patients had metabolic and radiological profiles suggestive of osteomalacia. Remarkable recovery was documented in all patients following oral cholecalciferol and calcium supplementation. Conclusions: Vitamin D deficiency is an important treatable cause of osteomalacic myopathy in Saudi Arabia. The diagnosis is frequently delayed or missed. Screening for Vitamin D deficiency in patients with acquired myopathy is needed to identify this treatable disorder. Toutes ont consulté pour une faiblesse musculaire proximale progressive présente depuis 6 à 24 mois (moyenne 14 mois) au moment de notre évaluation. La faiblesse était sévère chez 6 patientes (13%), au point que ces femmes étaient confinées à un fauteuil roulant. Des douleurs musculosquelettiques au dos, aux hanches ou aux membres inférieurs étaient présentes chez 66% des patientes. Un diagnostic d'ostéomalacie avait été posé chez seulement 11 patientes au moment où elles avaient été dirigées à un spécialiste et le diagnostic était erroné chez les 36 autres patientes (77%). Toutes les patientes avaient un profil métabolique et radiologique qui suggérait ce diagnostic. Une récupération remarquable a été observée chez toutes les patientes suite à la prise d'un supplément oral de cholécalciférol et de calcium. Conclusions : Un d...