Two new Brazilian patients with Gómez–López‐Hernández syndrome: Reviewing the expanded phenotype with molecular insights

Abstract

Gómez-López-Hernández (GLH) syndrome or cerebello-trigeminal dysplasia is a neurocutaneous syndrome whose etiology is unknown at the present time. We report two additional Brazilian patients, including the oldest one known to date (age 29). Here, we review the expanded phenotype in four patients with new clinical, psychiatric, radiological, and molecular investigations. One patient may have hypomania within the bipolar spectrum disorder with onset in childhood and adolescence. Primary growth hormone (GH) deficiency was ruled out in all patients, although one of them might have developed secondary GH deficiency due to partial hypopituitarism following severe hydrocephalus. Brain magnetic resonance angiography disclosed no azygous anterior cerebral artery (ACA) but only normal variants. Molecular analysis of the lysosomal acid phosphatase gene (ACP2) was performed, but no pathogenic mutations were identified. We present an overview of the phenotypic features of all patients described to date. There are currently 12 unrelated patients reported in the literature, 5 of whom are Brazilian. We discuss new molecular insights and speculate about the pathogenesis of GLH syndrome.

Gómez–López-Hernández syndrome: reappraisal of the diagnostic criteria

“…Parental consanguinity was reported only in one of 27 patients [6]. Males are markedly more likely to be affected than females (19 males, eight females), but in terms of disease severity, we did not found a gender-related difference.…”

Co-occurrence of Gomez-Lopez-Hernandez syndrome and Autism Spectrum Disorder: Case report with review of literature

“…Motor restlessness of the GLHS sufferer under our examination is not a new finding since it is observed in other studies of GLHS (4,10). Authors report on psychiatric problems such as hyperactivity, depression, self-injurious behavior and bipolar disorder in patients with GLHS (3,10,15). Co-occurrence of schizophrenia with GLHS is reported as well (11).…”

“…Similar to some GLHS sufferers (3,4,13,15) and in contrast to some other GLHS patients (3,8,9), J.K. is born to nonconsaguineous parents. At the same time, his parents do not have genetic abnormalities and they do not have witness to a case of marriage between relatives in their ancestors.…”

“…Rhombencephalosynapsis is observed not only in the case of GLHS, but as an isolated phenomenon as well as in combination with other brain malformations (1). Symptoms, concomitant to GLHS triad, are hydrocephalus, craniosynostosis, midfacial hypoplasia and low set ears, as well as bilateral corneal opacities, ocular hypertelorism-telecanthus, strabismus, clinodactyly of fifth fingers, short stature and intellectual impairment (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15).…”

“…To our knowledge, a total of 36 cases of GLHS have been described since the first reports of this clinical condition by Gomez (12) and Lopez-Hernandez (14). Symptomatology of GLHS varies from patient to patient (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) and further case studies are important to complete the clinical description of this disease.…”