Motor, Postural, and Communicative Phenotype in SHQ1-Related Neurodevelopmental Disorder with Dystonia and Seizures:...

Background: Biallelic variants in SHQ1 (SHQ1 homolog; H/ACA small nucleolar ribonucleoprotein assembly factor) cause neurodevelopmental disorder with dystonia and seizures (NEDDS), but descriptions of spontaneous motor organization, functional communication, and rehabilitation-relevant abilities remain limited. Case: We present a boy with infantile-onset epileptic encephalopathy, dystonia, cerebellar atrophy, and asymmetric spasticity in whom trio WES identified two heterozygous SHQ1 variants in trans: the maternally inherited c.5T>C (p.Leu2Pro) variant and the paternally inherited c.828_831del (p.Asp277SerfsTer27) variant. Both SHQ1 variants remain classified as variants of uncertain significance (VUS) under ACMG criteria. Based on the available genetic evidence, including segregation in trans, and the close phenotypic concordance, SHQ1-related NEDDS is considered the most likely clinical diagnosis; however, the molecular findings do not independently establish the diagnosis. At 5 years and 4 months, assessment combined neurological and physiotherapeutic examination, Vojta-derived Locomotion Stages, and an adapted, descriptive item-level Bayley-4 assessment conducted outside the normative age range. The child independently expressed LS 3 creeping, brief ineffective homologous lower-limb attempts, supported kneeling with goal-directed upward reaching, and intentional tablet-based augmentative and alternative communication despite severe expressive and motor limitations. Observed task performance during the adapted Bayley-4 assessment was heterogeneous and was interpreted solely descriptively because chronological age exceeded the normative range and administration required accommodations. After adjunctive cannabidiol was introduced, prolonged nocturnal tonic seizures requiring rescue medication became less frequent and subsequently ceased, whereas focal seizures persisted during wakefulness and overall daily seizure frequency did not show a comparable reduction. Because this was a single, unblinded observation with concomitant antiseizure-medication changes and no prospectively predefined, directly comparable observation windows, no quantitative or causal treatment effect can be inferred. The available rehabilitation exposure was reconstructed retrospectively from parental report; detailed treatment progression and standardized longitudinal outcomes were not recorded prospectively. Conclusions: The present case broadens the functional phenotype of SHQ1-related NEDDS and shows that standardized developmental testing alone may underestimate communicative intentionality and functionally expressed abilities when motor output is severely constrained. Integrated functional assessment can refine phenotyping and identify individualized rehabilitation and assistive mobility targets. The assessment-informed physiotherapy framework is clinical and hypothesis-generating; it was not prospectively evaluated and should not be interpreted as evidence of treatment efficacy.