Dual Diagnosis of Trichohepatoenteric Syndrome and Lipoid Proteinosis in a Turkish Child.

Introduction: Trichohepatoenteric syndrome (THES) is caused by pathogenic mutations in TTC37 and SKIV2L genes and characterized by intractable diarrhea, facial dysmorphism, hair abnormality, immunodeficiency, and skin abnormalities. Lipoid proteinosis is caused by pathogenic mutations in ECM1 gene and characterized by deposition of hyaline-like material in various tissues resulting in heterogenous clinical findings. Case Presentation: Four years after the diagnosis and management of THES, due to new clinical findings, another reason for underlying features of the patient was considered. WES was performed and a homozygous c.507delT (p.Arg171GlyfsTer7) mutation in the ECM1 gene was detected. Conclusion: This case provides an example of co-existence of multiple genetic defects in a single patient born to consanguineous parents.

Retinal detachment in a child with Frank-ter Haar syndrome.

BACKGROUND: To present a rare case of ocular involvement in a child with Frank-ter Haar syndrome (FTHS) presenting retinal detachment. MATERIALS AND METHODS: Detailed ophthalmological evaluation including examination under general anesthesia, ocular ultrasound, and visual evoked potential testing was completed. Photographic documentation of the physical findings was obtained. RESULTS: A 3-year-old female patient with FTHS was referred to evaluate for possible ophthalmic involvement. The patient presented with the classical dysmorphic abnormalities of the syndrome. Ophthalmologic evaluation revealed a high, against-the-rule corneal astigmatism in the right eye. In the left eye, the red reflex was absent with a suspicious membrane behind the lens, and a sensory exotropia was present. Ultrasonography confirmed retinal detachment with no history of previous trauma. Due to poor visual evoked potentials, no surgery was planned. Astigmatic refractive error was corrected with routine follow-up. CONCLUSIONS: FTHS is associated with multiple ocular involvement such as megalocornea, congenital glaucoma, or colobomas. This case report is the first to describe a high, against-the-rule astigmatism and retinal detachment in a female child with FTHS and demonstrates that an early and detailed ophthalmological examination is essential for these patients.

The utility of reverse phenotyping: a case of lysinuric protein intolerance presented with childhood osteoporosis.

OBJECTIVES: Childhood osteoporosis is often a consequence of a chronic disease or its treatment. Lysinuric protein intolerance (LPI), a rare secondary cause of the osteoporosis, is an autosomal recessive disorder with clinical features ranging from minimal protein intolerance to severe multisystemic involvement. We report a case diagnosed to have LPI using a Next Generation Sequencing (NGS) panel and evaluate the utility of reverse phenotyping. CASE PRESENTATION: A fifteen-year-old-boy with an initial diagnosis of osteogenesis imperfecta, was referred due to a number of atypical findings accompanying to osteoporosis such as splenomegaly and bicytopenia. A NGS panel (TruSight One Sequencing Panel) was performed and a novel homozygous mutation of c.257G>A (p.Gly86Glu) in the SLC7A7 gene (NM_001126106.2), responsible for LPI, was detected. The diagnosis was confirmed via reverse phenotyping. CONCLUSIONS: Reverse phenotyping using a multigene panel shortens the diagnostic process.

A New Cause of Obesity Syndrome Associated with a Mutation in the Carboxypeptidase Gene Detected in Three Siblings with Obesity, Intellectual Disability and Hypogonadotropic Hypogonadism

Objective: Carboxypeptidase E (CPE) plays a critical role in the biosynthesis of peptide hormones and neuropeptides in the endocrine system and central nervous system. CPE knockout mice models exhibit disorders such as diabetes, hyperproinsulinaemia, low bone mineral density and neurodevelopmental disorders. Only one patient is described with morbid obesity, intellectual disability, abnormal glucose homeostasis and hypogonadotropic hypogonadism, which was associated with a homozygous frameshift deletion in CPE. Methods: Herein are described three siblings with obesity, intellectual disability and hypogonadotropic hypogonadism. Whole exome sequencing (WES) was performed in the index case. Candidate variants were prioritised and segregation of the variant, consistent with the phenotype of the index case, was assessed by Sanger sequencing in affected siblings and parents. Results: WES analysis revealed a homozygous nonsense c.405C>A (p.Y135*) mutation in CPE. Validation and segregation analysis confirmed the homozygous mutation in the index case and his affected siblings. The parents were phenotypically normal heterozygous mutation carriers. Conclusion: This study provides additional evidence of the association between a homozygous nonsense mutation in CPE and a clinical phenotype consisting of obesity, intellectual disability and hypogonadotropic hypogonadism, which may be considered as a new monogenic obesity syndrome.

Clinical and Molecular Spectrum of Four Patients Diagnosed with Mowat-Wilson Syndrome.

Mowat-Wilson syndrome (MWS) is a rare autosomal dominant syndrome characterized by distinctive facial features, congenital heart defects, Hirschsprung disease, genitourinary anomalies, various structural brain anomalies, and intellectual disability. Pathogenic mutations that result in haploinsufficiency in the ZEB2 gene cause MWS. In this study, we aimed to evaluate the clinical features and molecular analysis results of 4 MWS patients. All patients were examined by an expert clinical geneticist. Dysmorphological abnormalities were recorded. Data including demographic, clinical, and laboratory findings were obtained from hospital records. ZEB2 gene analysis was performed using a Sanger sequencing method. All patients had typical facial features of MWS such as widely spaced eyes, broad eyebrows with a medial flare, low-hanging columella, prominent or pointed chin, open-mouth expression, and uplifted earlobes. Four different heterozygous mutations were identified; 2 mutations were frameshift (c.246_247delGGinsC, c.980_980delG), 1 was nonsense (c.2083C>T), and 1 was splice site (c.808-2A>G). Two of them (c.246_247delGGinsC, c.980_980delG) have not been previously reported in the literature. By defining 2 novel mutations, this study contributes to the molecular spectrum of MWS, while also providing a further insight for genetic counseling. It also demonstrates the importance of dysmorphological examination in clinical diagnosis.

Asthma control test and pediatric asthma quality of life questionnaire association in children with poor asthma control.

The aim of this study was to evaluate the association between Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and Asthma Control Test (ACT) in patients with poor asthma control. Children between 7-17 years of age with diagnosis of persistent asthma who are not on daily inhaler corticosteroid therapy were involved. At enrollment, sociodemographic and asthmatic characteristics were investigated and pulmonary function test (PFT), ACT and PAQLQ were administered. Patients were reevaluated following six week regular inhaler therapy and ACT, PAQLQ and PFT were performed. Out of 77 patients, 35 (45%) were female. The mean age was 11.62 ± 2.35 years. Following 6 weeks daily inhaler therapy, the scores of ACT, all the parameters of PAQLQ and all the parameters of PFT except FEV1/FVC were significantly increased (p < 0.05). There was a significant correlation between ACT and PAQLQ scores (r < 0.5, p=0.001). In conclusion, there is a correlation between ACT and PAQLQ.