ABSTRACT
In recent years, a rare form of autosomal recessive brachyolmia associated with amelogenesis imperfecta (AI) has been described as a novel nosologic entity. This disorder is characterized by skeletal dysplasia (e.g., platyspondyly, short trunk, scoliosis, broad ilia, elongated femoral necks with coxa valga) and severe enamel and dental anomalies. Pathogenic variants in the latent transforming growth factor-ß binding protein 3 (LTBP3) gene have been found implicated in the pathogenesis of this disorder. So far, biallelic pathogenic LTBP3 variants have been identified in less than 10 families. We here report a young boy born from consanguineous parents with a complex phenotype including skeletal dysplasia associated with aortic stenosis, hypertrophic cardiomyopathy, hypodontia and amelogenesis imperfecta caused by a previously unreported homozygous LTBP3 splice site variant. We also compare the genotypes and phenotypes of patients reported to date. This work provides further evidence that brachyolmia with amelogenesis imperfecta is a distinct nosologic entity and that variations in LTBP3 are involved in its pathogenesis.
Subject(s)
Amelogenesis Imperfecta/genetics , Latent TGF-beta Binding Proteins/genetics , Osteochondrodysplasias/genetics , Adolescent , Amelogenesis Imperfecta/complications , Amelogenesis Imperfecta/diagnosis , Consanguinity , Humans , Male , Osteochondrodysplasias/complications , Osteochondrodysplasias/diagnosis , Pedigree , Peru , Phenotype , Rare Diseases , Exome SequencingABSTRACT
OBJECTIVE: To describe the electroclinical features and the long-term outcomes of epilepsy in a large cohort of males and females with Down syndrome who developed epilepsy in childhood. STUDY DESIGN: Subjects with Down syndrome and cryptogenic epilepsy with onset in childhood were identified retrospectively from the databases of 16 Italian epilepsy centers over a 40-year period. For each subject, age at onset of seizures, seizure semiology and frequency, electroencephalography characteristics, treatment with antiepileptic drugs, and long-term clinical and electroencephalography outcomes were analyzed. RESULTS: A total of 104 subjects (64 males [61.5%], 40 females [38.5%]) were identified. Seizure onset occurred within 1 year of birth in 54 subjects (51.9%), between 1 and 12 years in 42 subjects (40.4%), and after 12 years in 8 subjects (7.7%). Males had a younger age of seizure onset than females. Of the 104 subjects, 51 (49.0%) had infantile spasms (IS), 35 (33.7%) had partial seizures (PS), and 18 (17.3%) had generalized seizures (GS). Febrile seizures were recorded in 5 (4.8%) subjects. Intractable seizures were observed in 23 (22.1%) subjects, including 5 (9.8%) with IS, 8 (44.4%) with PS, and 10 (31.3%) with GS. CONCLUSION: Cryptogenic epilepsy in Down syndrome may develop during the first year of life in the form of IS or, successively, as PS or GS. Electroclinical features of IS resemble those of idiopathic West syndrome, with a favorable response to treatment with adrenocorticotropic hormone seen. Patients experiencing PS and GS may be resistant to therapy with antiepileptic drugs.
Subject(s)
Down Syndrome/complications , Epilepsy/complications , Epilepsy/physiopathology , Adolescent , Anticonvulsants/therapeutic use , Child , Child, Preschool , Electroencephalography , Epilepsy/drug therapy , Female , Humans , Infant , Male , Retrospective Studies , Time FactorsABSTRACT
The phenotypical characteristics in 20 children with achondroplasia were examined in relation to the occurrence of polyhydramnios. A history of polyhydramnios (9 of 20 cases) was associated with a lower height (SD) (P <.05), more severe shortening of the lower segment and upper limbs (P =.0001), and higher frequency of left-handedness (P =.0081).