Achondroplasia (ACH; MIM #100,800), caused by a heterozygous gain of function pathogenic variant in the fibroblast growth factor receptor 3 gene (FGFR3; MIM*134,934), is the most prevalent and most readily identifiable cause of disproportionate short stature that is compatible with life. In addition, individuals with achondroplasia face significant medical, functional, and psychosocial challenges throughout their lives. This study assessed associated morbidities in patients with achondroplasia at a single center in Turkey. In this study, the clinical findings and associated morbidities of a group of patients with achondroplasia (n = 68) with clinical multidisciplinary follow-up at a single center between the years 2005–2023 are evaluated retrospectively. A total of 68 patients, 30 male (44.1%) and 38 female (55.9%), were evaluated. In the majority (84.2%) of patients, shortness of extremities was detected in the prenatal period at an average of 28.7 gestational weeks (± 3.6 SDS) with the aid of ultrasonography. More than half (n = 34/63, 54%) of the patients had a father of advanced paternal age (≥ 35 years). Among the complications, respiratory system manifestations, including obstructive sleep apnea (70%), ear-nose-throat manifestations including adenoid hypertrophy (56.6%) and otitis media (54.7%), neurological manifestations due to foramen magnum stenosis (53.2%), and skeletal manifestations including scoliosis (28.8%), are represented among the most common. The mortality rate was 7.3% (n = 5/68).Conclusion: This study not only represents the first retrospective analysis of the associated morbidities of patients with achondroplasia from a single center in Turkey but also will provide a reference point for future studies.

TP63-related disdorders broadly involve varying combinations of ectodermal dysplasia (sparse hair, hypohydrosis, tooth abnormalities, nail dysplasia), cleft lip/palate, acromelic malformation, split-hand/foot malformation/syndactyly, ankyloblepharon filiforme adnatum, lacrimal duct obstruction, hypopigmentation, and hypoplastic breasts and/or nipples. TP63-related disorders are associated with heterozygous pathogenic variants in TP63 and include seven overlapping phenotypes; Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC), Ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome 3 (EEC3), Limb-mammary syndrome (LMS), Acro-dermo-ungual-lacrimal-tooth syndrome (ADULT), Rapp-Hodgkin syndrome (RHS), Split-hand/foot malformation 4 (SHFM4), and Orofacial cleft 8. We report on five unrelated families with 8 affected individuals in which the probands presented with varying combinations of ectodermal dysplasia, cleft lip/palate, split-hand/foot malformation, lacrimal duct obstruction, and ankyloblepharon filiforme adnatum. The clinical diagnosis involved AEC syndrome (2 patients), EEC3 syndrome (2 patients), and a yet hitherto unclassified TP63-related disorder. Sanger sequence analysis of the TP63 gene was performed revealing five different variants among which four were novel and three were de novo. The identificated TP63 variants co-segregated with the other affected individuals in the families. The abnormalities of ectoderm derived structures including hair, nails, sweat glands, and teeth should alert the physician to the possibility of TP63-related disorders particularly in the presence of orofacial clefting.

ADPRHL2 is involved in posttranslational modification and is known to have a role in physiological functions such as cell signaling, DNA repair, gene control, cell death, and response to stress. Recently, a group of neurological disorders due to ADPRHL2 variants is described, characterized by childhood-onset, stress-induced variable movement disorders, neuropathy, seizures, and neurodegenerative course. We present the diagnostic pathway of two pediatric patients with episodic dystonia and ataxia, who later had a neurodegenerative course complicated by central hypoventilation syndrome due to the same homozygous ADPRHL2 variant. We conducted a systematic literature search and data extraction procedure following the Preferred Reporting Items for Systematic Review and Meta-Analysis 2020 statement in terms of patients with ADPRHL2 variants, from 2018 up to 3 February, 2023. In total, 12 articles describing 47 patients were included in the final analysis. Median age at symptom onset was 2 (0.7–25) years, with the most common presenting symptoms being gait problems (n = 19, 40.4%), seizures (n = 16, 34%), ataxia (n = 13, 27.6%), and weakness (n = 10, 21.2%). Triggering factors (28/47; 59.5%) and regression (28/43; 60.4%), axonal polyneuropathy (9/23; 39.1%), and cerebral and cerebellar atrophy with white matter changes (28/36; 77.7%) were the other clues. The fatality rate and median age of death were 44.6% (n = 21) and 7 (2–34) years, respectively. ADPRHL2 variants should be considered in the context of episodic, stress-induced pediatric and adult-onset movement disorders and seizures.

Introduction: Jaberi-Elahi syndrome is a rare autosomal recessive neurodevelopmental disorder caused by biallelic loss-of-function variants in GTPBP2, a gene involved in ribosome-associated quality control. The condition shows marked phenotypic heterogeneity, including microcephaly, hypotonia or spasticity, developmental delay, intellectual disability, movement disorders, epilepsy, and variable neuroimaging findings. Case Presentation: We report a 4-month-old female infant born to consanguineous parents, presenting with severe microcephaly, developmental delay, hypotonia, and craniofacial features. Additional findings included left-sided pes equinovarus, secundum atrial septal defect, and periventricular white matter abnormalities on brain magnetic resonance imaging. No overt ectodermal abnormalities were observed. Ophthalmological examination revealed no structural anomalies; however, detailed retinal evaluation and electroretinography could not be performed. During follow-up, the patient developed early-onset seizures requiring antiepileptic treatment. Clinic exome sequencing identified a novel homozygous frameshift variant in GTPBP2 (c.1165_1166del; p.(Leu389GlufsTer26)), classified as likely pathogenic. This homozygous variant was absent in population databases, and segregation analysis confirmed parental heterozygosity. This represents the first reported case with Jaberi-Elahi syndrome from Türkiye. Conclusion: Jaberi-Elahi syndrome should be considered in infants with severe congenital microcephaly, developmental delay, seizures, and craniofacial features, particularly in the context of consanguinity and abnormal brain magnetic resonance imaging. This report expands the molecular and clinical spectrum of Jaberi-Elahi syndrome.