Clinical and molecular evaluation of 13 Brazilian patients with Gomez-López-Hernández syndrome

Am J Med Genet A. 2021 Apr;185(4):1047-1058. doi: 10.1002/ajmg.a.62059. Epub 2020 Dec 31.


We aim to characterize patients with Gomez-López-Hernández syndrome (GLHS) clinically and to investigate them molecularly. A clinical protocol, including a morphological and neuropsychological assessment, was applied to 13 patients with GLHS. Single-nucleotide polymorphism (SNP) array and whole-exome sequencing were undertaken; magnetic resonance imaging was performed in 12 patients, including high-resolution, heavily T2-weighted sequences (HRT2) in 6 patients to analyze the trigeminal nerves. All patients presented alopecia; two did not present rhombencephalosynapsis (RES); trigeminal anesthesia was present in 5 of the 11 patients (45.4%); brachycephaly/brachyturricephaly and mid-face retrusion were found in 84.6 and 92.3% of the patients, respectively. One patient had intellectual disability. HRT2 sequences showed trigeminal nerve hypoplasia in four of the six patients; all four had clinical signs of trigeminal anesthesia. No common candidate gene was found to explain GLHS phenotype. RES does not seem to be an obligatory finding in respect of GLHS diagnosis. We propose that a diagnosis of GLHS should be considered in patients with at least two of the following criteria: focal non-scarring alopecia, rhombencephalosynapsis, craniofacial anomalies (brachyturrycephaly, brachycephaly or mid-face retrusion), trigeminal anesthesia or anatomic abnormalities of the trigeminal nerve. Studies focusing on germline whole genome sequencing or DNA and/or RNA sequencing of the alopecia tissue may be the next step for the better understanding of GLHS etiology.

Keywords: Gomez-Lopéz-Hernández; Rhombencephalosynapsis; focal alopecia; trigeminal anesthesia; whole exome sequencing.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / diagnostic imaging
  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / pathology
  • Acid Phosphatase / genetics*
  • Adolescent
  • Adult
  • Alopecia / diagnosis
  • Alopecia / diagnostic imaging
  • Alopecia / genetics*
  • Alopecia / pathology
  • Brazil / epidemiology
  • Cerebellum / abnormalities*
  • Cerebellum / diagnostic imaging
  • Cerebellum / pathology
  • Child
  • Child, Preschool
  • Craniofacial Abnormalities / diagnosis
  • Craniofacial Abnormalities / diagnostic imaging
  • Craniofacial Abnormalities / genetics*
  • Craniofacial Abnormalities / pathology
  • Exome Sequencing*
  • Female
  • Growth Disorders / diagnosis
  • Growth Disorders / diagnostic imaging
  • Growth Disorders / genetics*
  • Growth Disorders / pathology
  • Humans
  • Infant
  • Infant, Newborn
  • Magnetic Resonance Imaging
  • Male
  • Neurocutaneous Syndromes / diagnosis
  • Neurocutaneous Syndromes / diagnostic imaging
  • Neurocutaneous Syndromes / genetics*
  • Neurocutaneous Syndromes / pathology
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • Rhombencephalon / diagnostic imaging
  • Rhombencephalon / pathology
  • Trigeminal Nerve / diagnostic imaging
  • Trigeminal Nerve / metabolism
  • Trigeminal Nerve / pathology
  • Young Adult


  • ACP2 protein, human
  • Acid Phosphatase

Supplementary concepts

  • Gomez Lopez Hernandez syndrome