Morison Lottie D, Vogel Adam P, Christodoulou John, Gold Wendy A, Verden Dylan, Chung Wendy K, Braden Ruth, Bredebusch Joanna, Kaur Simranpreet, Scheffer Ingrid E, Morgan Angela T
Speech and Language Team, Murdoch Children's Research Institute, Parkville, VIC, Australia.
Department of Audiology and Speech Pathology, The University of Melbourne, Parkville, VIC, Australia.
Eur J Hum Genet. 2025 May 16. doi: 10.1038/s41431-025-01867-0.
KIF1A-associated neurological disorder (KAND) is a genetic condition characterised by motor, cognitive and ophthalmologic features. The speech and language phenotype have not been systematically analysed. Here, we assess speech and language using observer- and clinician-reported outcomes, and performance outcome measures. 44 individuals (25 female) with KAND (median age 7 years, range 1-60 years) participated. Median age at diagnosis was 4 years (range 0.5-58 years). KIF1A variants were missense (41/44 individuals, 93%), intragenic deletion (2/44, 5%) and splice site (1/44, 2%). Age at first words was delayed (>12 months) in 38/44 (86%) individuals. At assessment, 28/44 (64%) combined words into sentences and all of the 20 individuals assessed had dysarthria. Apraxic speech features and phonological impairments occurred in children aged under 8 years. 36/37 (97%) participants had language impairment, with expressive language skills stronger than receptive (p = 0.02) and written (p = 0.03) language on the Vineland Adaptive Behaviour Scales. 7/32 (22%) caregivers reported speech and language regression. Mild to severe intellectual disability occurred in 31/33 (94%) individuals. 22/44 (50%) participants had used augmentative and alternative communication, such as key word sign or speech generating devices. Individuals had average social motivation skills in contrast to moderately impaired social cognition, communication and awareness on the Social Responsiveness Scale (p < 0.05). 16/44 (36%) had epilepsy and 40/44 (91%) had visual impairment, namely nystagmus (16/44, 36%), optic nerve atrophy and strabismus (both 12/44, 27%). Individuals with KAND frequently have speech and language disorders necessitating early and targeted speech and language interventions.
KIF1A相关神经障碍（KAND）是一种具有运动、认知和眼科特征的遗传性疾病。其言语和语言表型尚未得到系统分析。在此，我们使用观察者和临床医生报告的结果以及表现性结果测量方法来评估言语和语言。44名患有KAND的个体（25名女性）参与了研究（中位年龄7岁，范围1 - 60岁）。诊断时的中位年龄为4岁（范围0.5 - 58岁）。KIF1A变体为错义突变（41/44个体，93%）、基因内缺失（2/44，5%）和剪接位点突变（1/44，2%）。44名个体中有38名（86%）首次说话的年龄延迟（>12个月）。在评估时，44名中有28名（64%）能将单词组合成句子，且接受评估的20名个体均有构音障碍。8岁以下儿童出现失用性言语特征和语音障碍。37名参与者中有36名（97%）有语言障碍，在《韦氏儿童智力量表》上，表达性语言技能强于接受性（p = 0.02）和书面（p = 0.03）语言。32名照料者中有7名（22%）报告有言语和语言退化。33名个体中有31名（94%）有轻度至重度智力残疾。44名参与者中有22名（50%）使用过辅助和替代沟通方式，如关键词手势或言语生成设备。与在《社会反应量表》上中度受损的社会认知、沟通和意识相比，个体的社会动机技能处于平均水平（p < 0.05）。44名中有16名（36%）患有癫痫，44名中有40名（91%）有视力障碍，即眼球震颤（16/44，36%）、视神经萎缩和斜视（均为12/44，27%）。患有KAND的个体经常有言语和语言障碍，需要早期且有针对性的言语和语言干预。
