De novo pathogenic variants in the GATAD2B gene have been associated with a syndromic neurodevelopmental disorder (GAND) characterized by severe intellectual disability (ID), impaired speech, childhood hypotonia, and dysmorphic features. Since its first description in 2013, nine patients have been reported in case reports and a series of 50 patients was recently published, which is consistent with the relative frequency of GATAD2B pathogenic variants in public databases. We report the detailed phenotype of 19 patients from various ethnic backgrounds with confirmed pathogenic GATAD2B variants including intragenic deletions. All individuals presented developmental delay with a median age of 2.5 years for independent walking and of 3 years for first spoken words. GATAD2B variant carriers showed very little subsequent speech progress, two patients over 30 years of age remaining non-verbal. ID was mostly moderate to severe, with one profound and one mild case, which shows a wider spectrum of disease severity than previously reported. We confirm macrocephaly as a major feature in GAND (53%). Most common dysmorphic features included broad forehead, deeply set eyes, hypertelorism, wide nasal base, and pointed chin. Conversely, prenatal abnormalities, non-cerebral malformations, epilepsy, and autistic behavior were uncommon. Other features included feeding difficulties, behavioral abnormalities, and unspecific abnormalities on brain MRI. Improving our knowledge of the clinical phenotype is essential for correct interpretation of the molecular results and accurate patient management.

GATAD2B基因的从头致病变体已与症状严重的智能障碍（ID），语言障碍，儿童低渗症和畸形特征相关的综合症神经发育障碍（GAND）。自2013年首次描述以来，已在病例报告中报告了9名患者，最近发表了一系列50例患者，这与公共数据库中GATAD2B致病变异的相对频率一致。我们报告了19名来自不同种族背景的患者的详细表型，并确认了致病性GATAD2B变体，包括基因内缺失。所有个体均出现发育迟缓，独立行走的中位年龄为2.5岁，首次说话的中位年龄为3岁。GATAD2B变异携带者随后的言语进展很少，两名年龄超过30岁的患者仍保持非语言能力。内脏疾病多为中度至重度，其中一例为严重病例，一例为轻度病例，显示疾病严重性范围较先前报道的广。我们确认巨头畸形是GAND的主要特征（53％）。最常见的畸形特征包括额头宽大，眼睛深陷，眼前肌过度，鼻基宽和下巴尖。相反，产前异常，非脑畸形，癫痫和自闭症行为并不常见。其他特征包括进食困难，行为异常和脑MRI的非特异性异常。改善我们对临床表型的了解对于正确解释分子结果和准确的患者管理至关重要。