Trigeminal nerve agenesis with absence of foramina rotunda in Gómez-López-Hernández syndrome.

Gómez-López-Hernández syndrome (GLHS) is a clinical condition traditionally characterized by rhombencephalosynapsis (RS), parieto-occipital alopecia, and trigeminal anesthesia. It is a neurocutaneous disorder with no known etiology. The underlying cause of the trigeminal anesthesia in GLHS has not been examined or reported; it has merely been identified on clinical grounds. In this report, a 10-month-old white female born at 37 weeks gestational age with GLHS underwent a contrast-enhanced CT for the evaluation of craniofacial dysmorphic features. Thin-section bone algorithm images showed absence of bilateral foramina rotunda and trigeminal nerve fibers. The maxillary branch of the trigeminal nerve passes through the foramen rotundum and carries sensory information from the face. This case is unique because trigeminal nerve absence has not been suggested as a possible etiology for trigeminal anesthesia associated with GLHS. It is not known how many cases of GLHS have agenesis of the trigeminal nerve; however, a review of the literature suggests that this patient is the first. The triad of RS, alopecia, and trigeminal anesthesia is specific to GLHS; therefore, early identification of trigeminal nerve agenesis in patients with RS could expedite diagnosis of GLHS, particularly given that the clinical diagnosis of trigeminal anesthesia in neonates is a challenging one. Diagnosing alopecia in newborns is likewise challenging. Early diagnosis could allow for early intervention, especially for ophthalmic complications, which are known to have significant long-term effects. This case illustrates the benefits of CT imaging in the detection of trigeminal nerve and foramina rotunda abnormalities in neonates with suspected GLHS.

Jervell and Lange-Nielsen syndrome in a father and daughter from a large highly inbred family: a 16-year follow-up of 59 living members.

OBJECTIVE: To report the autosomal dominant inheritance of the Jervell and Lange-Nielsen syndrome in a highly inbred family, the initiation of Torsades de Pointes, and the natural history of the syndrome based on a 16-year follow-up of the kindred. METHOD: A family tree was constructed that included 66 blood relatives from three successive generations. Electrocardiograms were obtained from 59 living members including the proband, four members from a nuclear family, and 54 from the extended family. Evoked response audiometry was recorded for the proband and the nuclear family. All 59 family members were followed up regularly for 16 years. RESULTS: A total of 24 living members were affected--QTc: 480-680 ms. The proband had long QTc, bilateral high-tone sensorineural deafness, recurrent syncope, and Torsades de Pointes. The asymptomatic father had long QTc and unilateral high-tone sensorineural deafness that involved specifically the left ear. One asymptomatic sibling of the proband had long QTc and normal hearing. The mother and another sibling were asymptomatic; QTc and hearing were normal in both. A total of 21 affected members from the extended family had only long QTc, and all were asymptomatic. There were three congenitally deaf first cousins who had recurrent syncope and adrenergic-triggered sudden death. In all, seven of 10 parents had consanguineous marriage to a first cousin. Each affected offspring had at least one affected parent. The severely symptomatic proband who received only ß-blocker therapy and the 23 affected members without antiadrenergic therapy, all remained asymptomatic throughout the 16-year follow-up period. CONCLUSION: Jervell and Lange-Nielsen syndrome was inherited as autosomal dominant in this kindred. The majority of the affected members had a mild phenotype. The severity of auditory and cardiac phenotypes corresponded.

ABCA12 is the major harlequin ichthyosis gene.

Harlequin ichthyosis (HI) is the most severe form of autosomal-recessive, congenital ichthyosis. Affected infants have markedly impaired barrier function and are more susceptible to infection. Abnormalities in the localization of epidermal lipids as well as abnormal lamellar granule formation are features of HI skin. Previously, we and others have shown that mutations in the ABCA12 gene encoding an adenosine triphosphate-binding cassette (ABC) transporter underlie the skin disease HI. In this study, we have sequenced the ABCA12 gene in an additional 14 patients and show that all contain mutations, with the majority being either nonsense substitution or frameshift mutations. Eleven HI patients had bi-allelic ABCA12 mutations, whereas in the remaining three HI patients in this study, ABCA12 mutations were detected on only one allele by sequencing. In addition, the one patient from the previous study where no sequence mutations were detected was screened for heterozygous deletions. A combination of oligonucleotide arrays, multiplex PCR analysis and single-nucleotide polymorphism genotyping revealed a heterozygous intragenic deletion in exon 8. These mutation data establish ABCA12 as the major HI gene.