Agrin, encoded by AGRN, plays a vital role in the acetylcholine receptor clustering pathway, and any defects in this pathway are known to cause congenital myasthenic syndrome (CMS) 8 in early childhood with variable fatigable muscle weakness. The most severe or lethal form of CMS manifests as a fetal akinesia deformation sequence (FADS). To date, only one family has been reported with an association of null variants in AGRN and a lethal FADS.

Kohlschütter-Tönz (KTS) is a rare autosomal recessive, genetically heterogeneous disorder characterized by a triad of early-onset seizures, global developmental delay or regression, and amelogenesis imperfecta of both temporary and permanent teeth. To date, 66 cases have been reported in the literature, of which 44 with genetic confirmation.

This study aimed to elucidate the fetal ultrasound characteristics, pathology, and molecular genetic etiology of autosomal recessive tubular dysplasia.

Spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMD-JL1) is an extremely rare skeletal dysplasia belonging to a group of disorders called linkeropathies. It is characterized by skeletal and connective tissue abnormalities. Biallelic variants in genes encoding enzymes that synthesize the tetrasaccharide linker region of glycosaminoglycans lead to linkeropathies, which exhibit clinical and phenotypic features that overlap with each other. SEMD-JL1 results in impaired growth and short stature, along with increased joint flexibility leading to limb joint dislocations and progressive spinal deformity.

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome (MIM# 208250) is a rare monogenic disorder, characterized by early onset of camptodactyly, progressive coxa vara, bilateral arthropathy and constrictive pericarditis. The syndrome is caused by biallelic loss-of-function variants in PRG4 . Deficiency of PRG4 results in progressive worsening of joint deformity with age. Thirteen individuals with CACP syndrome from eight consanguineous Indian families were evaluated. We used exome sequencing to elucidate disease-causing variants in all the probands. These variants were further validated and segregated by Sanger sequencing, confirming the diagnosis of CACP syndrome in them. Seven females and six males aged 2-23 years were studied. Camptodactyly (13/13), coxa vara (11/13), short femoral neck (11/13) and arthritis in large joints (12/13) [wrists (11/13), ankle (11/13), elbow (10/13) and knee (10/13)] were observed commonly. Five novel disease-causing variants (c.3636G>T, c.1935del, c.1134dup, c.1699del and c.962T>A) and two previously reported variants (c.1910_1911del and c.2816_2817del) were identified in homozygous state in PRG4 . We describe the phenotype and mutations in one of the large cohorts of patients with CACP syndrome, from India.

Prader-Willi syndrome (PWS) is a rare and complex genetic disorder caused by the loss of expression of the paternal copy of the imprinted genes on chromosome 15q11-q13. A variety of findings have been reported on the phenotypic differences between the genetic subtypes of PWS. This article compares the clinical findings of 57 PWS patients by genetic subtype and explores possible associations in this context.

Biallelic variants in thiamine pyrophosphokinase 1 ( TPK1 ) are known to cause thiamine metabolism dysfunction syndrome 5 (THMD5). This disorder is characterized by neuroregression, ataxia and dystonia with basal ganglia abnormalities on neuroimaging. To date, 27 families have been reported with THMD5 due to variants in TPK1 .

Neurodevelopmental disorders (NDDs) comprise conditions that emerge during the child's development and contribute significantly to global health and economic burdens. De novo variants in CNOT3 have been linked to NDDs and understanding the genotype-phenotype relationship between CNOT3 and NDDs will aid in improving diagnosis and management.