Chromosome 7q11.23 duplication syndrome presenting as neuropsychiatric regression in late adolescence: A new manifestation of a new syndrome?

To the Editor

Chromosome 7q11.23 duplication syndrome (C7DS) was first described in 2005 and is an autistic-like syndrome of speech and language delay, social anxiety, hypotonia, characteristic facies, developmental delay, childhood apraxia, dysarthria, expressive language disorder, attention difficulties and extreme shyness (Morris et al., 2015). Affected persons often have an unusual stance and walking style, enlarged head, chronic constipation, joint laxity and an increased risk of heart defects (Morris et al., 2015). We describe an unusual presentation of functional decline in adolescence leading to a diagnosis of de novo C7DS. As far as we are aware, this is the first reported case of a diagnosis being made due to the development of a regression syndrome, rather than typical early childhood developmental delay.

A 17-year-old adolescent male presented after 18 months of functional decline manifesting as social isolation and school refusal. He had developed subtle gait abnormalities, a stiff and robotic manner, vocal changes, dysarthria, jaw-clenching, grimaces and unusual blinking. He displayed odd behaviours with stereotypies, excessive and repetitive cleaning, ambitendency and obsessional slowness in daily tasks. His memory became impaired, with inability to recall recent autobiographical information. His affect was blunted and he was apathetic, alexithymic and ambivalent. He had severe poverty of speech and thought content, but he denied perceptual disturbances or passivity phenomena on direct questioning. Neuropsychological testing showed executive dysfunction with slow information processing speed, concretism and poor problem solving.

He had no prior medical history or mental health problems, and family history was unremarkable other than one older sibling with Down Syndrome. His was a planned pregnancy, uneventful birth, good attachment and no reported separation anxiety as a child. He was reported as being a ‘very shy child’, but otherwise met normal developmental milestones.

Investigations included standard blood tests for possible first-episode psychosis, as well as anti-NMDA and anti-VGKC antibodies, serum/urine amino acids and copper which were all normal. Brain magnetic resonance imaging (MRI), electroencephalography (EEG), lumbar puncture, echocardiography and sleep studies were normal. Yale–Brown Obsessive Compulsive Scale (Y-BOCS) showed some mild to moderate checking and cleaning compulsions, but no obsessional aspects, and below threshold for obsessive–compulsive disorder (OCD). Catatonia rating scales were non-diagnostic, and he showed no response to lorazepam challenge. Chromosomal microarray results returned a diagnosis of C7DS. His parents were tested and did not carry the duplication.

Treatment consisted of a combination of olanzapine 5 mg and escitalopram 30 mg which resulted in improved affect and reactivity, with a marked reduction in slowness and repetition of tasks. His memory and speech improved; however, he never returned to premorbid function.

In hindsight, the patient displayed many of the physical and psychological features of this syndrome; however his case was unusual in that his symptoms developed after previous normal functioning, without obvious developmental delays in early childhood. The cause of his regression in late adolescence is unclear. Puberty or some other psychological stressors may have ‘unmasked’ previously unnoticed symptoms, or his presentation maybe either a variant of the catatonic regression syndrome seen in adolescents with Down Syndrome (Mircher et al., 2017) or a form of prodromal or atypical psychosis/schizophrenia, for which there is an increased risk with this disorder (Mulle et al., 2014).