Mandibuloacral dysplasia type A in childhood.

Mandibuloacral dysplasia type A (MADA) is characterized by growth retardation, postnatal onset of craniofacial anomalies with mandibular hypoplasia, progressive acral osteolysis, and skin changes including mottled pigmentation, skin atrophy, and lipodystrophy. Owing to its slowly progressive course, the syndrome has been recognized in adults, and pediatric case reports are scarce. We present the clinical case of two children in whom the diagnosis of MADA was made at an unusually early age. A 5-year-old boy presented with ocular proptosis, thin nose, and short and bulbous distal phalanges of fingers. A 4-year-old girl presented with round face and chubby cheeks, thin nose, bulbous fingertips, and type A lipodystrophy. In both, a skeletal survey showed wormian bones, thin clavicles, short distal phalanges of fingers and toes with acro-osteolysis. Both children were found to be homozygous for the recurrent missense mutation, c.1580G>A, (p.R527H) in exon 9 of the LMNA gene. Thus, the phenotype of MADA can be manifest in preschool age; diagnosis may be suggested by short and bulbous fingertips, facial features, and lipodystrophy, supported by the finding of acral osteolysis, and confirmed by mutation analysis.

Massive hemobilia and papillomatosis of the gallbladder in metachromatic leukodystrophy: a life-threatening condition.

Polyposis of the gallbladder is rare during childhood. This condition can be associated with three other conditions: metachromatic leukodystrophy, Peutz-Jeghers' syndrome, and pancreaticobiliary maljunction. We report the case of a child with hemobilia in metachromatic leukodystrophy, which rendered cholecystectomy necessary. Macroscopically, the gallbladder measured 4.6 cm in length and showed an opaque serous surface and focal brown petechiae. Moreover, a yellow polypoid lesion of 2 cm in diameter and a diffuse thickening of the fundus wall were observed. Many reports describe the importance of the association of gallbladder papillomatosis with metachromatic leukodystrophy, but only three cases presented with massive intestinal bleeding, such as our young patient had. It is thus imperative that this life-threatening condition should be well known.

Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus (MPPH): report of a new case.

Megalencephaly (MEG), or enlargement of the brain, can either represent a familial variant with normal cerebral structure, or a rare brain malformation associated with developmental delay and neurological problems. MEG has been split into two subtypes: anatomical and metabolic. The latter features a build-up inside the cells owing to metabolic causes. Anatomical MEG has been detected in many different conditions, including many overgrowth syndromes. In 2004 Mirzaa et al. reported five non-consanguineous patients with a new MCA/MR syndrome characterized by severe congenital MEG with polymicrogyria (PMG), postaxial polydactyly (POLY) and hydrocephalus (HYD). The authors argued that these findings identified a new and distinct malformation syndrome, which they named MPPH. We report on a new case of MPPH, the first to be described after the original series (Mirzaa et al., 2004).

Anophthalmos with limb anomalies (Waardenburg opththalmo-acromelic syndrome): report of a new Italian case with renal anomaly and review.

Anophthalmos with limb anomalies (Waardenburg Opththalmo-Acromelic Syndrome) is a very rare autosomal recessive multiple congenital anomaly syndrome, first described by Waardenburg et al. in 1961 (MIM 206920). It is characterized by mono or more often bilateral anophthalmia/microphthalmia and foot malformations, which can be observed in 91% of the patients. The most common anomaly of the feet is the presence of four toes. The hands are affected bilaterally in 77% of the cases. The most characteristic anomaly is the synostosis of the fourth and fifth metacarpals. To date, 33 cases from 19 families have been reported. We present an Italian case of anophthalmia with limb anomalies and a renal malformation, which has never been described in the literature.

MRI and neurological findings in macrocephaly-cutis marmorata telangiectatica congenita syndrome: report of ten cases and review of the literature.

MRI and neurological findings in macrocephaly-cutis marmorata telangiectatica congenita syndrome: report of ten cases and review of the literature: We describe the clinical history and magnetic resonance imaging (MRI) findings in 10 children with the Macrocephaly-Cutis Marmorata Telangiectatica Congenita syndrome (M-CMTC--MIM 602501). This syndrome has recently been delineated within the general group of patients with Cutis Marmorata Telangiectatica (CMTC) as a distinct and easily recognisable entity. In contrast to most children with CMTC, patients with M-CMTC syndrome have a high risk of neurological abnormalities, such as hydrocephalus, megalencephaly, developmental delay and mental retardation. An MRI scan showed structural cerebral abnormalities in all of our patients, including megalencephaly, asymmetry of the cerebral hemispheres and abnormally increased signal of white matter. Seven patients also had Chiari type I malformation. Reviewing all reported cases, we propose appropriate surveillance for known complications.

Albright's hereditary osteodystrophy (pseudohypoparathyroidism type Ia): clinical case with a novel mutation of GNAS1.

Albright's hereditary osteodystrophy is characterized by ectopic calcification and ossification, round face, short hands and feet with short terminal phalanges, short metacarpals (especially 4th and 5th) and absence of the 4th knuckle (brachydactyly type E). Here we describe a case that recently came to our attention of a girl suffering from seizures caused by hypocalcaemia, in which the clinical diagnosis of Albright's hereditary osteodystrophy and Pseudohypoparathyroidism (PHP) (Pseudohypoparathyroidism Ia) was confirmed by DNA molecular analysis. This analysis revealed a novel mutation of GNAS 1, resulting in the nonsense mutation of exon 13 (CAG-->TAG, codon 384). This result expands the spectrum of GNAS1 mutations associated with this disorder.

Genitourinary anomalies in Mowat-Wilson syndrome with deletion/mutation in the zinc finger homeo box 1B gene (ZFHX1B). Report of three Italian cases with hypospadias and review.

Hypospadias, when the urethra opens on the ventral side of the penis, is a common malformation seen in about 3 per 1,000 male births. It is a complex disorder associated with genetic and environmental factors and can be part of genetic syndromes. Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype, Hirschsprung disease, microcephaly and mental retardation. It is caused by mutations in the zinc finger homeo box 1B gene, ZFHX1B (SIP1). To date, 68 deletion/mutation-positive cases have been reported. Genitourinary anomalies are common in MWS. Here we report that hypospadias is common in males with this syndrome. In 39 patients where this information was available, hypospadias was present in 46% of patients (18/39). In the 3 Italian male cases reported here, hypospadias was always present. MWS should be considered by endocrinologists in patients with hypospadias associated with developmental delays/mental retardation, in particular in the presence of a distinct facial phenotype.

Solitary median maxillary central incisor syndrome: clinical case with a novel mutation of sonic hedgehog.

Solitary median maxillary central incisor (SMMCI) is a rare dental anomaly. It is usually considered as a minor manifestation of holoprosencephaly (HPE). Some reported families had severe cases of HPE in some members and SMMCI in others. Mutations of Sonic Hedgehog (SHH) have been documented in these families. SMMCI has also been found as an isolated finding or together with other anomalies such as microcephaly, short stature, endocrine pathology, and choanal atresia. We describe a patient with SMMCI and a novel SHH mutation: Val332Ala.

Marden-Walker syndrome: case report, nosologic discussion and aspects of counseling.

The Marden-Walker syndrome is characterized by a mask-like face with blepharophimosis, micrognathia, cleft or high-arched palate, low-set ears, congenital joint contractures, decreased muscular mass, failure to thrive and psychomotor retardation. We report a boy with a phenotype mostly resembling the condition named Marden-Walker syndrome, with many of the criteria proposed for diagnosing this particular phenotype. In addition he had hypoplastic corpus callosum, cerebellar vermis hypoplasia, enlarged cisterna magna and vertebral abnormalities. During pregnancy there were reduced fetal movements. In the present patient the fetal hypokinesia sequence, due to central nervous system malformation, is most compatible with the diagnosis of Marden-Walker syndrome. The etiology is probably heterogeneous, but the possibility of autosomal recessive inheritance should be considered in genetic counseling.

[Care recommendations for type 1 neurofibromatosis]. / Raccomandazioni assistenziali per la neurofibromatosi tipo 1.

Neurofibromatosis type 1 (NF1) is a progressive, multisystem disorder affecting about 1:3000 individuals. About one third of patients show serious complications and about one half are mildly affected. Since the original National Institutes of Health Consensus Conference in 1987, that established the clinical criteria for the diagnosis of NF1, there has been significant progress toward a more complete understanding of the molecular bases for NF1, and our knowledge of the natural history and management of the NF1 has significantly improved. Despite these advances, the diagnosis of NF1 is still based largely on clinical criteria and no individual prognostic evaluation or definitive medical therapy are available. The recommendations for the care of NF1 patients and their families are constantly changing: according to the new guidelines, the mainstay of management is anticipatory guidance and surveillance for treatable complications; surveillance usually includes annual follow-up visits, unless symptoms call for more frequent visits or more accurate diagnostic evaluation.

[Genetics of type 1 neurofibromatosis]. / Genetica della neurofibromatosi tipo 1 (NF1).

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterised by cafè au lait spots, multiple neurofibromas and Lisch nodules of the iris, with marked variability of expression. The NF1 gene is located at 17q11.2, spans 350 kb genomic DNA and comprises 60 exons encoding a 11-13 kb transcript (Viskochil et al.). Four alternatively spliced NF1 transcripts have been identified and they show differential expression in various tissues. NF1 gene is a member of the tumor suppressor gene family. The protein encoded by NF1, neurofibromin, has a domain homologous to the GTPase activating protein (GAP) family, and downregulates ras activity. Neurofibromin is involved in the control of cellular growth and differentiation and germline mutation analysis has shown that around 82% of all the fully characterised NF1 specific mutations so far predict severe truncation of neurofibromin. The current demand for molecular diagnosis of NF1 is low. Many couples would probably request a prenatal diagnosis if it could predict disease severity. Molecular prediction of disease severity and prognosis may either be very complicated or even impossible. Presymptomatic DNA diagnosis is probably not going to be in huge demand because the clinical diagnosis of NF1 is usually straightforward, even in early childhood. Further knowledge of the gene function may also lead to the development of new therapy for the disease.

[Use of palivizumab in the prevention of syncytial virus respiratory infection]. / Uso del palivizumab nella prevenzione dell'infezione da virus respiratorio sinciziale.

BACKGROUND: Monthly intramuscular Palivizumab (Synagis, MedImmune, Inc.) is effective in reducing the incidence of RSV-attributable hospitalization by 55% if compared with placebo and seems to be well tolerated. METHODS: Our clinical experience in the use of palivizumab in RSV-prophylaxis is presented. During autumn-winter 1999-2000, a total of 8 newborns (gestational age between 28-34 weeks) in our neonatal intensive care unit (NICU) met the AAP recommendations for RSV-immunoprophylaxis. Palivizumab was monthly administered at a dosage of 15 mg/kg i.m. at discharge from the NICU and during the RSV season. Infants were followed up to 40 days from the last injection for adverse reactions and clinical data. RESULTS: Among eligible newborns, two (28 and 29 weeks respectively) were affected by CLD and required medical therapy at discharge, 4 were born at 29-32 weeks and 2 (both of them born at 34 weeks) had additional risk factors of infection (crowded environment, passive smoking). During RSV season, none of the infants experienced RSV-hospitalization nor lower respiratory tract infection. Mild and transient adverse effects occurred in 2 cases out of 8 (induration in the site of injection and irritability). CONCLUSIONS: In our series of patients, palivizumab resulted safe and effective.

Oculo-auriculo-vertebral spectrum in Klinefelter syndrome.

We report a boy with classical 47,XXY Klinefelter syndrome (KS) and oculo-auriculo-vertebral spectrum (OAV). Two patients with KS and OAV were reported previously. Also, the combination of bilateral aplasia of the mandibular ramus and condyle and KS has been documented. The present observation supports the view that the cause of hemifacial microsomia appears heterogeneous and that OAV may be part of the spectrum of craniofacial anomalies associated with KS.

Double-blind study of nimesulide in divers with inflammatory disorders of the ear, nose and throat.

200 divers of either sex, aged 18 to 54 years, entered a double-blind study to compare the efficacy and tolerability of nimesulide 200 mg/day with those of seaprose S 60 mg/day in the treatment of nonbacterial inflammatory disorders of the ear, nose, and throat. At the end of the 1-week treatment period, both drugs were judged to be effective, with improvements and, in most cases, complete remission of all symptoms observed. Nimesulide showed greater clinical efficacy, and both drugs were well tolerated.