Title

Clinical Presentation of a Complex Neurodevelopmental Disorder Caused by Mutations in ADNP.

Journal

Biological psychiatry

Volume

85

Issue

None

Pages

287-297

Date

2019-02-15

Authors

Gozes I | Van Dijck A | Kooy RF | ADNP Consortium. | Bernier R | Cappuyns E | Eichler EE | Kleefstra T | Kvarnung M | Küry S | Lindstrand A | Mancini GM | Meuwissen ME | Nordgren A | Romano C | Rosenfeld JA | Tzschach A | Vandeweyer G | Vulto-van Silfhout AT | de Vries BBA | van der Werf IM

Fifty-two percent of the individuals in this cohort present with severe intellectual disability at the age of assessment, 36% have a moderate disability and 12% have a mild disability.

Developmental delay is present in all individuals, with motor delay being one of the key features.

Seventy-eight percent of the children had hypotonia, while hypertonia was present in three children.

Another key feature is speech delay which presents in 98.6% of individuals.

Sixteen percent have seizures, including absence seizures, focal seizures with reduced awareness, epilepsy with Continuous Spike and Waves during Slow Wave Sleep (CSWS), or unclassified seizures.

Ninety-three percent of the individuals present with autistic features (Fig. 3-B). Sixty-seven percent of them have been reported to have a clinical diagnosis of ASD.

Sixty-seven percent have also been diagnosed with sensory processing disorder.

Several present with obsessive compulsive behavior, mood disorder, a high anxiety level, temper tantrums, self-injurious and (verbally) aggressive behavior.

Forty-four percent of the individuals are hyperactive or easily distracted. About one third of them have a diagnosis of Attention Deficit Hyperactivity Disorder (ADHD).

Sleep problems are present in 65.2%.

Fifty-six percent of them appeared to have cerebral abnormalities, including atypical white matter lesions, delayed myelination, cortical dysplasia or atrophy, perinatal hypoxic ischemic encephalopathy, hydrocephalus, and hippocampal hypoplasticity (Fig. 3-C)

Visual problems were present in 73.6% of the individuals, especially hypermetropia (40.3%) and strabismus (49.2%), but also myopia and astigmatism (Fig. 3-E).

Interestingly, individuals with a p.Tyr719* mutation start walking at 3.5 years, significantly later than the 2 years and 2 months of the remainder of the cohort (p<0.0001, One Way Anova).

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