Assessment of dysphagia in infants with facial malformations.

In infants with facial malformation, dysphagia is frequent and can lead to respiratory and nutritional complications whatever the phenotype. The aim of our study was to assess the severity and mechanisms of dysphagia in infants with facial malformations in order to guide therapeutic management. Forty-two newborn infants with dysphagia and recognizable malformation patterns other than isolated Pierre Robin sequence had: (1) needle electromyography (EMG) of muscles of the face, tongue, and soft palate; (2) two-channel EMG during bottle feeding; and (3) esophageal manometry (EM). The results were compared by clinical dysphagia-grading groups and by age at cessation of enteral feeding. Although micrognathia (86%) and cleft or high-arched palate (76%) were common, the key clinical finding that correlated with the likelihood of respiratory complications was glossoptosis (p<0.01). EMG signs of denervation correlated with respiratory complications (p<0.05) and the duration of enteral feeding (p<0.01). EMG during bottle feeding showed disturbed motor organization at the pharyngeal level in 27 of 37 patients. The severity of pharyngeal incoordination correlated with the duration of enteral feeding (p<0.025). All 21 patients examined by EM had dysfunction at the esophageal level. Thus, in the assessment of upper digestive tract dysfunction, our clinical grading system, EMG, and EM yield convergent information that is relevant to the management of dysphagic infants with facial malformations. Much of the information is obtainable only from EMG.

22q11.2 duplication syndrome: two new familial cases with some overlapping features with DiGeorge/velocardiofacial syndromes.

Twenty-one patients, including our two cases, with variable clinical phenotype, ranging from mild learning disability to severe congenital malformations or overlapping features with DiGeorge/velocardiofacial syndromes (DG/VCFS), have been shown to have a chromosome duplication 22q11 of the region that is deleted in patients with DG/VCFS. The reported cases have been identified primarily by interphase FISH and could have escaped identification and been missed by routine cytogenetic analysis. Here we report on two inherited cases, referred to us, to rule out 22q11 microdeletion diagnosis of VCFS. The first patient was a 2-month-old girl, who presented with cleft palate, minor dysmorphic features including short palpebral fissures, widely spaced eyes, long fingers, and hearing loss. Her affected mother had mild mental retardation and learning disabilities. The second patient was a 7(1/2)-year-old boy with velopharyngeal insufficiency and mild developmental delay. He had a left preauricular tag, bifida uvula, bilateral fifth finger clinodactyly, and bilateral cryptorchidism. His facial features appeared mildly dysmorphic with hypertelorism, large nose, and micro/retrognathia. The affected father had mild mental retardation and had similar facial features. FISH analysis of interphase cells showed three TUPLE1-probe signals with two chromosome-specific identification probes in each cell. FISH analysis did not show the duplication on the initial testing of metaphase chromosomes. On review, band q11.2 was brighter on one chromosome 22 in some metaphase spreads. The paucity of reported cases of 22q11.2 microduplication likely reflects a combination of phenotypic diversity and the difficulty of diagnosis by FISH analysis on metaphase spreads. These findings illustrate the importance of scanning interphase nuclei when performing FISH analysis for any of the genomic disorders.

X-linked lissencephaly with absent corpus callosum and ambiguous genitalia (XLAG): clinical, magnetic resonance imaging, and neuropathological findings.

X-linked lissencephaly with absent corpus callosum and ambiguous genitalia is a newly recognized syndrome responsible for a severe neurological disorder of neonatal onset in boys. Based on the observations of 3 new cases, we confirm the phenotype in affected boys, describe additional MRI findings, report the neuropathological data, and show that carrier females may exhibit neurological and magnetic resonance imaging abnormalities. In affected boys, consistent clinical features of X-linked lissencephaly with absent corpus callosum and ambiguous genitalia are intractable epilepsy of neonatal onset, severe hypotonia, poor responsiveness, genital abnormalities, and early death. On magnetic resonance imaging, a gyration defect consisting of anterior pachygyria and posterior agyria with a moderately thickened brain cortex, dysplastic basal ganglia and complete agenesis of the corpus callosum are consistently found. Neuropathological examination of the brain shows a trilayered cortex containing exclusively pyramidal neurons, a neuronal migration defect, a disorganization of the basal ganglia, and gliotic and spongy white matter. Finally, females related to affected boys may have mental retardation and epilepsy, and they often display agenesis of the corpus callosum. These findings expand the phenotype of X-linked lissencephaly with absent corpus callosum and ambiguous genitalia, may help in the detection of carrier females in affected families, and give arguments for a semidominant X-linked mode of inheritance.