GATAD2B-associated neurodevelopmental disorder (GAND) syndrome: a case report

*Correspondence: [e-mail].

Abstract

Case Presentation: LFPC, age 5, daughter of non-consanguineous and healthy parents, born at 33 weeks of gestational age, vaginal delivery with polyhydramnios, Apgar score of 3/6. Was born with apnea, hypotonia and bradycardia and admitted to an intensive care unit for invasive ventilatory support for 04 days. Negative blood cultures. No history of seizures, with an unaltered head ultrasound and normal neonatal screenings. Karyotype 46, XX, requested while still in the NICU, as they noticed low implantation of ears and alteration of the cranial conformation since birth. Parents noted global delay in neuropsychomotor development at 6 months old, showing global hypotonia, weight gain difficulties, weak crying and vomiting, initiated with follow-up with a Pediatric Neurologist and therapies, Speech Therapy, Psychology and Occupational Therapy. Started autonomous walk at the age of 2, speaks few words, has good interaction with people, has a good understanding of orders despite a reduced vocabulary. On physical examination, macrocephaly was noted, dolichocephaly, wide font, facial hypomimia, sparse eyebrows, shiper-folded ear with amputation of the left lobe, in addition to clinodactyly of the fifth finger in both hands. Brain MRI showed a slight prominence of the subarachnoid space in the frontal and temporal convexities, suggesting immaturity of the cerebrospinal fluid drainage system. Electroencephalogram noted mild to moderate diffuse disorganization of the basic activity. Evaluation carried out with Geneticist, with genetic microarrays normal. Ultimately, exome sequencing revealed the presence of pathogenic mutation in the GATAD2B gene (NM_020699.4 c.346C>T p. (arg116*). Therefore, the patient presents clinical phenotype, confirmed by molecular examination of GATAD2B-associated neurodevelopmental disorder (GAND) Syndrome.

Discussion: GAND Syndrome includes phenotypes with intellectual disability, global developmental delay with limited speech and language, and characteristic face. Several additional phenotypic features were recently identified, including polyhydramnios, neonatal feeding difficulties, infant hypotonia, delayed motor milestones, long, thin fingers, ocular abnormalities (strabismus). It may also include aortic valve defects, epilepsy (focal and/or primary generalized), abnormal brain MRI, and macrocephaly.

Final Comments: It is essential to keep multidisciplinary follow-up of these patients, in order to stimulate and guarantee the greatest potential for neuropsychomotor development.

Publication History

Article published online:
12 May 2025