Macrocranium and macrencephaly in neurofibromatosis

Data were collected on 52 patients (30 males and 22 females) with neurofibromatosis. Using the volumetric method of Gordon, it was found that 44% of the patients had cranial capacities above the 95th percentile (70% were above the 50th percentile). The presence of intracranial tumors and/or hydrocephalus did not influence skull size. Four patients above the 95th percentile had normal pneumoencephalograms and cerebral angiograms, indicating that the cause of the macrocranium, in some instances at least, is macrencephaly. Volumetric measurement of the sella turcica in 27 of the 52 patients gave results which strongly suggest that idiopathic enlargement of the sella in neurofibromatosis is uncommon, if not rare. Skull films of 26 patients with tuberous sclerosis did not show an increase in cranial capacity similar to that found in neurofibromatosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46770/1/256_2004_Article_BF00347724.pd

Associations between language development and skin conductance responses to faces and eye gaze in children with autism spectrum disorder

Attention to social stimuli is associated with language development, and arousal is associated with the increased viewing of stimuli. We investigated whether skin conductance responses (SCRs) are associated with language development in ASD: a population that shows abnormalities in both attention to others and language development. A sample of 32 children with ASD (7 y – 15 y; M =9 y) was divided into two groups, based on language onset histories. A typically developing comparison group consisted of 18 age and IQ matched children. SCRs were taken as the participants viewed faces. SCRs differentiated the ASD group based on language onset and were associated with abnormal attention to gaze in infancy and subsequent language development

Holoprosencephaly

Holoprosencephaly (HPE) is a complex brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and the 28th day of gestation and affecting both the forebrain and the face. It is estimated to occur in 1/16,000 live births and 1/250 conceptuses. Three ranges of increasing severity are described: lobar, semi-lobar and alobar HPE. Another milder subtype of HPE called middle interhemispheric variant (MIHF) or syntelencephaly is also reported. In most of the cases, facial anomalies are observed in HPE, like cyclopia, proboscis, median or bilateral cleft lip/palate in severe forms, ocular hypotelorism or solitary median maxillary central incisor in minor forms. These latter midline defects can occur without the cerebral malformations and then are called microforms. Children with HPE have many medical problems: developmental delay and feeding difficulties, epilepsy, instability of temperature, heart rate and respiration. Endocrine disorders like diabetes insipidus, adrenal hypoplasia, hypogonadism, thyroid hypoplasia and growth hormone deficiency are frequent. To date, seven genes have been positively implicated in HPE: Sonic hedgehog (SHH), ZIC2, SIX3, TGIF, PTCH, GLI2 and TDGF1. A molecular diagnosis can be performed by gene sequencing and allele quantification for the four main genes SHH, ZIC2, SIX3 and TGIF. Major rearrangements of the subtelomeres can also be identified by multiplex ligation-dependent probe amplification (MLPA). Nevertheless, in about 70% of cases, the molecular basis of the disease remains unknown, suggesting the existence of several other candidate genes or environmental factors. Consequently, a "multiple-hit hypothesis" of genetic and/or environmental factors (like maternal diabetes) has been proposed to account for the extreme clinical variability. In a practical approach, prenatal diagnosis is based on ultrasound and magnetic resonance imaging (MRI) rather than on molecular diagnosis. Treatment is symptomatic and supportive, and requires a multidisciplinary management. Child outcome depends on the HPE severity and the medical and neurological complications associated. Severely affected children have a very poor prognosis. Mildly affected children may exhibit few symptoms and may live a normal life

Median cleft lip with holoprosencephaly

Australian Paediatric Journal9131-34AUPJ