Francesca Macucci

Magnesium profile in autism.

The aim of the present study was to determine and compare plasma and erythrocyte concentrations of magnesium in 12 autistic children (10 boys, 2 girls), 17 children with other autistic spectrum disorders (14 boys, 3 girls), 5 girls with classic Rett syndrome, and 14 normal children (7 boys, 7 girls) of the same age. No differences in intracellular Mg were found between controls and pathological subjects; however, autistic children and children with other autistic spectrum disorders had significantly lower plasma concentrations of Mg than normal subjects (p=0.013 and p=0.02, respectively). Although our study population was small, we conclude that children with autistic spectrum disorders require special dietary management. If these cases are diagnosed at an early stage, they can be helped through diet.

The FBN1 (R2726W) mutation is not fully penetrant

The R2726W mutation in the fibrillin 1 (FBN1, Marfan syndrome) gene segregates with isolated skeletal features of Marfan syndrome and/or high stature. Here we report a family in which two out of four individuals, an 18‐year‐old son and his mother, a 41‐year‐old woman, had the R2726W mutation of FBN1. Both family members carrying the mutation were of average height. The son had a Marfan‐like phenotype, but his mother did not. The FBN1 R2776W mutation, which is associated with skeletal features of Marfan syndrome, appears incompletely penetrant. Consequently, genetic counselling in the presence of this mutation is difficult.

A child with vestibular neuritis : Is adenovirus implicated?

Vertigo in children is relatively under examined in the literature. Among its causes, vestibular neuritis (VN) represents only 2% of cases, with its etiology remaining unknown. We report for the first time a 4-year-old boy with vestibular neuritis and serological results compatible with adenoviral infection. Serological diagnosis was performed on the basis of a rise and consequent normalization of complement fixation (CF) titers of the plasma antibodies. Although we were not able to detect exactly when the infection started, we were able to detect an increased level of adenovirus antibodies by CF titers, followed by a decrease (i.e. 1/16, then 1/8, then <1/4) during the recovery. This is typical of a resolving infection. Furthermore, that this increase in antibodies was specific to an adenovirus infection was suggested by the observation that we did not detect increases in antibodies to other common viruses (i.e. herpes simplex and zoster viruses, Epstein-Barr virus, cytomegalovirus, influenza and parainfluenza viruses). This allows us to exclude the chance of nonspecific antibody activation. We concluded that, although our data do not formally demonstrate an involvement of adenovirus in VN, they suggest such an involvement. This may be of interest, given that a viral etiology for VN has been proposed but not definitively proven.

Neurocutaneous syndrome with mental delay, autism, blockage in intracellular vescicular trafficking and melanosome defects

We evaluated a 11‐year‐old male patient with mental delay, autism and brownish and whitish skin spots. The former resembled those of neurofibromatosis, the latter those of tuberous sclerosis. The patient received a complete clinical work‐up to exclude neurofibromatosis, tuberous sclerosis, or any other known neurocutaneous disease, with biochemistry, chromosome analysis and analysis of skin specimens. Being all the other tests not significant, two main ultrastructural defects were observed. The first was a blockage in intracellular vescicular trafficking with sparing of the mitochondria; the second an aberrant presence of melanosomes in vacuoles of several cell lines and abnormal transfer of these organelles to keratinocytes. This patient presented with a unique clinical picture distinct from neurofibromatosis or tuberous sclerosis or any other known neurocutaneous disease. The ultrastructural abnormalities suggested a defect in cell trafficking involving several cell lines and compartments.

Hypertelorism, ptosis, and myopia associated with drug‐resistant epilepsy, mental delay, growth deficiency, ectodermal defects, and osteopenia

We report a 30‐year‐old woman with hypertelorism, ptosis, and myopia associated with drug‐resistant epilepsy (DRE, Lennox–Gastaut syndrome), mental delay, growth deficiency, ectodermal defects, and osteopenia. To the best of our knowledge, this patient has an unusual combination of symptoms not previously described, associated with severe central nervous system dysfunction. The ectodermal defects were present in a very intriguing form, were difficult to diagnose, and did not conform to any classification or previous description.

Novel CNS syndrome and ectodermal dysplasia

Ectodermal dysplasia (ED) syndromes, extensively reviewed by Pinheiro and Freire-Maia [1994], are an ever-growing group of complex nosologic conditions whose delineation and classification were first proposed by Freire-Maia [1971, 1977: for more details, see Pinheiro and Freire-Maia, 1994]. We describe a novel CNS syndrome with ectodermal dysplasia. Before the skin biopsy, the diagnosis was delayed for several years. The proband was a 5-year-old child (Fig. 1) who was referred with delayed neurological and psychomotor development and epilepsy due to neonatal hypoxia. The mother and father (not consanguineous) and the younger brother are apparently healthy subjects. After an uneventful pregnancy, at term the child was born weighing 2,850 g (10th centile), length 49 cm (25th centile) and head circumference 34 cm (25th centile). At the delivery, a poorly specified ‘‘newborn hypoxia’’ was reported. Delayed psychomotor development was apparent at an early stage. The boy was referred for seizures at age 16-months old and underwent anticonvulsant drug therapy. His physical growth was normal. In-born errors of metabolism were ruled out. His karyotype was normal: 46,XY. Magnetic resonance imaging (MRI) of his central nervous system, performed using lowresolution thick slices at age 3 and 16 months, showed apparentlynormalbrainmorphology.Notwithstanding, perinatal hypoxic-ischemic encephalopathy was considered the major cause of his problems, although this was doubtful. At the age of 5 years, when he was referred to our clinic (Fig. 1), we noted a tower-like skull, a 30 55-mm lancet-shaped patch of alopecia (i.e., triangular temporal alopecia) in the right lateral scalp, generalized hypotonia, and rare dystonic movements of the four limbs. His hair varied in density, with alternate locks of normal and very thin hairs; the latter are probably vellus hairs (for macroscopic and microscopic/ ultrastructural details, see Fig. 2). His hands and feet showed slight clinodactyly (fifth finger, and third and fourth toes: images not shown).His armsand limbswere normally proportioned with no rhizomelic shortening. The thorax showed a slight asymmetry of themammary areolae (right side greater than the left), and a base of apparent normal mammary tissue was present in the upper right side (confirmed ultrasonically: image not shown). No structural abnormalities of gland structure could be detected, as gland biopsy could not be performed for ethical reasons. Serum prolactin levels were normal. His weight was 13.9 kg (3rd centile), his height was 104 cm (25th centile), and his head circumference was 49.5 cm (10th–25th centile). Neurological examination showed severemental deficiency, andhewasunable towalk.He showedgeneralizedhypotonia, rare dystonic movements of the four limbs, and weak deep tendon reflexes. An ophthalmological examination showed retinal dystrophy (abnormal pigmentation) and slightly pale optic discs bilaterally. An electroencephalogram (EEG) showed paroxysmal discharges (spike and spikewaves) on the bilateral centro-temporal regions, mainly in the right side, and anticonvulsant drugs were still necessary to control his seizures. A brain MRI, performed using a high field-strength magnet (1.5 T) with high resolution thin slices (Fig. 3), showed plagiocephaly, cerebral hemisphere asymmetry (right side> left side), and small symmetric areas of signal hyperintensity corresponding to both thalami, the right lenticular nucleus and the prerolandic areas. These lesions were probably glial tissue areas. There were no apparent areas of cortical dysplasia or periventricular heterotopia. A skin biopsywas performed (Figs. 4 and 5), not in the triangular area of temporal alopecia, but in an apparently normal area of the scalp (the right lower temporo-occipital area). This showed several microscopic skin defects. These included a reduced number of hair follicles, some of which were of the vellus type; sebaceous gland hypoplasia; abnormal position of the eccrine sweat glands, very close to the hair follicles; areas lacking immunostaining for filaggrin, and hyperkeratosis of the hair follicle (Fig. 4). The skin ultrastructure showed signs of degeneration, with aberrant melanosomes and disorganized collagen fiber spirals (Fig. 5). A muscle biopsy was normal. We describe here a novel CNS syndrome with a wide spectrumof physical features: a tower-like skull,mental deficiency, neuromotor delay, cerebral hemispheres asymmetry, retinal dystrophy, hypotonia, dystonia, epilepsy, joint laxity, triangular temporal alopecia, and defective skin, hair and mammalian gland development. In some features, it was similar to the GomezLopez-Hernandez syndrome or cerebellotrigeminal *Correspondence to: R. Zannolli, M.D., Department of Pediatrics, Obstetrics, and Reproductive Medicine, Policlinico Le Scotte, University of Siena, Siena, Italy. E-mail: zannolli@unisi.it

Polydactyly With Ectodermal Defect, Osteopenia, and Mental Delay

Five members from 3 generations, including a 35-year-old woman and her 2 sons, both mentally impaired to a different degree, were studied in a tertiary care hospital. Anamnestic, clinical, neurological, and radiological evaluations were used to describe phenotypes. A and B postaxial polydactyly, transmitted likely as autosomal dominant, was associated with an extensive variability of phenotypic features: (1) cutaneous syndactyly, (2) nail–teeth dysplasia, (3) osteopenia, and (4) mental delay. The likelihood that the constellation of observations we report here is caused by mutation of a single gene that subsequently affects multiple physiological activities, although fascinating, remains to be proven. Instead, we hypothesize that it likely develops as a contiguous gene syndrome.

Familial Robertsonian 13;14 Translocation With Mental Retardation and Epilepsy

Familial reports of a robertsonian translocation in more than two generations are rare. We report three generations (a daughter, the mother, and the mothers father) with a heterozygous, balanced robertsonian translocation t(13;14)(q11;q11). Central nervous system disease was present, but differentially expressed, in generations I and III. The daughter presented with mental delay and epilepsy, and the mother was apparently healthy, whereas the mothers father was again symptomatic, with borderline intelligence. Fluorescent in situ hybridization analysis was performed to exclude a loss or gain of chromosomal material. No uniparental disomy was present. We concluded that genetic counseling in the presence of this rearrangement was extremely difficult, independent of the affected parent being symptomatic or asymptomatic. (J Child Neurol 2006;21:531—533; DOI 10.2310/7010.2006.00098).