A novel RAD21 mutation in a boy with mild Cornelia de Lange presentation: Further delineation of the phenotype.

Cornelia de Lange syndrome is a rare autosomal dominant or X-linked developmental disorder characterized by characteristic facial dysmorphism, intellectual disability, growth retardation, upper limb and multiorgan anomalies. Causative mutations have been identified in five genes coding for the cohesion complex structure components or regulatory elements. Among them, RAD21 is associated with a milder phenotype. Very few RAD21 intragenic mutations have been identified so far. Thus, any new patient is a valuable tool to delineate the associated phenotype. We discuss a new patient with RAD21 confirmed molecular diagnosis and compare his clinical features to those of previously described patients carrying different RAD21 intragenic mutations.

Biallelic mutations in RTTN are associated with microcephaly, short stature and a wide range of brain malformations.

Biallelic mutations in the RTTN gene have been reported in association with microcephaly, short stature, developmental delay and malformations of cortical development. RTTN mutations have previously shown to link aberrant ciliary function with abnormal development and organization of the human cerebral cortex. We here report three individuals from two unrelated families with novel mutations in the RTTN gene. The phenotype consisted of microcephaly, short stature, pachygyria or polymicrogyria, colpocephaly, hypoplasia of the corpus callosum and superior vermis. These findings provide further confirmation of the phenotype related to pathogenic variants in RTTN.

Hypomyelination and congenital cataract: broadening the clinical phenotype.

OBJECTIVE: To further delineate the clinical spectrum of hypomyelination and congenital cataract (HCC), a rare autosomal recessive white matter disorder due to deficiency of a membrane protein, hyccin, encoded by FAM126A. DESIGN: Case reports and literature review. SETTING: University hospital. PATIENTS: Nine additional patients with HCC. RESULTS: Cataract was congenital in 5 patients; it was found at 4, 5, and 7 months in 3 patients, and only a mild lens opacity was noted at age 3 years in the remaining patient. Neurologic presentation was at birth in 1 child, was characterized by developmental delay at the end of the first year of life in 7 patients, and was characterized by sudden motor regression in the second year of life in the remaining patient. Three patients were able to walk with support only, 5 achieved the ability to walk without support, and the remaining patient was not able to stand at age 2 years. Mental retardation was present in all patients. Peripheral neuropathy was present in the 8 patients who underwent neurophysiological investigations. Brain magnetic resonance imaging showed hypomyelination associated with periventricular white matter abnormalities in all patients and brainstem pyramidal tract involvement in 8. Molecular analysis depicted 3 novel mutations and the previously reported IVS5 + 1G>T mutation. CONCLUSIONS: Our study broadens the clinical spectrum of HCC. The clinical variability ranges from severe early-onset neurologic impairment to a milder phenotype. In contrast to this clinical variability, the peculiar magnetic resonance pattern of hypomyelination combined with increased periventricular white matter water content allows distinction of HCC from other forms of hypomyelinating leukoencephalopathies.

Meningitis with subdural empyema due to non-typhoid Salmonella in a 9-month-old girl.

We report a case of a 9-month-old baby admitted to the hospital because of low-grade fever, focal seizures in a context of watery diarrhea for 14 days' duration. The patient workup revealed a mild neutrophilic pleocytosis on cerebrospinal fluid (46 cells/microl), a positive stool culture for Salmonella pomona sensitive to ceftriaxone and ciprofloxacin, and a subdural empyema (SDE) on the cerebral MRI. The child received an intravenous third-generation cephalosporin for 4 weeks which resulted in cure. This case highlights an unusual extra-intestinal complication of non-typhoid salmonella infection. Involvement of the central nervous system with non-typhoidal salmonellosis is an important complication that can result in significant morbidity if not recognized and treated promptly. A focal intra-cranial infection must be considered in the differential diagnosis of any child presenting with focal seizures and gastroenteritis due to Salmonella. Appropriate diagnostic imaging of the head (cerebral CT scan with contrast and/or MRI) is mandatory to exclude the presence of an intra-cranial complication, even in the presence of negative CSF culture for Salmonella. Subfrontal and subtemporal SDE are sometimes missed on axial CT scans and better appreciated on MRI. Non-surgical treatment of small subdural empyemas with prolonged intravenous antibiotic therapy is a therapeutic option.

Pseudo-Bartter syndrome in a pregnant mother and her fetus.

Pseudo-Bartter syndrome presents the same clinical and biological characteristics as Bartter syndrome but without primary renal tubule abnormalities. We relate the case of a premature baby presenting at birth with severe hypokalemic metabolic alkalosis associated with hyponatremia and hypochloremia. Maternal blood at the time of delivery showed the same electrolyte perturbations. The baby's mother had suffered from anorexia and vomiting during pregnancy. A few weeks after birth the baby's blood abnormalities had almost returned to normal. Chloride depletion is at the origin of both maternal and fetal hypokalemic alkalosis.