Clinical phenotype of FOXP1 syndrome: parent-reported medical signs and symptoms in 40 individuals.

BACKGROUND: The first studies on patients with forkhead-box protein P1 (FOXP1) syndrome reported associated global neurodevelopmental delay, autism symptomatology, dysmorphic features and cardiac and urogenital malformations. The aim of this study was to assess the prevalence of congenital abnormalities in an unbiased cohort of patients with FOXP1 syndrome and to document rare complications. METHODS: Patients with FOXP1 syndrome were included, mostly diagnosed via whole-exome sequencing for neurodevelopmental delay. A parent-report questionnaire was used to assess medical signs and symptoms, including questions about features rated as most burdensome by patients and their family. RESULTS: Forty individuals were included, 20 females and 20 males. The mean age at assessment was 13.2 years (median 8.5 years; range 2-54 years; ≥18 years n = 7). Seven adults were included. All patients had developmental problems, including cognitive, communication, social-emotional and motor delays. The most prevalent medical signs and symptoms include delayed bladder control, sleeping problems, hypermetropia, strabismus, sacral dimple, undescended testes, abnormal muscle tone and airway infections. The most burdensome complaints for patients with FOXP1 syndrome, as perceived by parents, include intellectual disability, impaired communication, behaviour problems, lack of age-appropriate self-reliance, attention problems and anxiety. According to parents, patients have quite similar reported symptoms, although incontinence, obsessions and a complex sensory profile have a higher ranking. CONCLUSION: The results of this study may be used to further guide medical management and identify patient priorities for future research targeted on those features of FOXP1 syndrome that most impair quality of life of patients and their families.

A standardised mini pig model for in vivo investigations of anticholinergic effects on bladder function and salivation.

PURPOSE: The objective was to validate an in vivo model for evaluation of pharmacological effects on bladder function taking the most predominant anticholinergic side effect (hyposalivation) into account. Therefore, two anticholinergic properties (propiverine hydrochloride and tolterodine-L(+)-tartrate) were used to test the in vivo model. Sacral anterior root stimulation (SARS) was performed to induce reproducible and standardized bladder contractions. To evaluate hyposalivation standardised salivavary flow measurements by stimulating the lingual nerve was performed in addition to SARS. MATERIALS AND METHODS: 10 male mini pigs were anaesthetised. The carotid artery was cannulated for blood pressure measurement and the jugular vein for administration of propiverine 0.4 mg kg(-1) b.w. and tolterodine 0.06 mg kg(-1) b.w. For stimulation-induced salivary flow measurements both lingual nerves were exposed and a cuff electrode was placed around the nerves. The bladder was exposed and a cystostomy catheter was inserted to performed cystometrographic measurements during SARS. RESULTS: In all experiments, for each animal reproducible intravesical pressure values (pves) and salivary flow rates were elicited during electrostimulation before administration of the drug. Bladder pressure: After administration of propiverine, neurostimulation-induced rise in pves had fallen by 60% from the initial value. After administration of tolterodine pves had fallen by about 50%. After additional administration of atropine pves decreased to about 15% of the initial value for both drugs. Salivation: After propiverine salivary flow had fallen by 61%. Inhibition of salivary flow under tolterodine was about 56%. Additional administration of atropine led in both drugs to a nearly complete blockade of salivation. Heart rate (HR) and blood pressure (BP): Directly following intravenous administration of both drugs, a short-term and reversible period of mild but significant fluctuations in HR was observed. There was also a slight but non-significant rise in blood pressure. CONCLUSIONS: This model allows comparative investigations of various drugs with bladder inhibitory properties in terms of acute efficacy and side effects.