A Biomechanical Investigation of Children with Type 1 Diabetes Mellitus: Are Children's Feet a Precursor to Adulthood Foot Complications?

BACKGROUND: There is limited evidence on the biomechanical effects of type 1 diabetes mellitus (T1DM) on children's feet. This study aimed to determine whether children living with T1DM aged 10 to 16 years have altered foot structure and gait parameters compared with same-aged children without medical conditions. METHODS: A nonexperimental, case-control study was conducted. Thirty-four healthy children and children living with T1DM were recruited. Participants underwent a clinical biomechanical examination followed by instrumented gait analysis using the Oxford Foot Model to investigate foot segment motion. RESULTS: Children with T1DM demonstrated more dermatologic lesions and structural foot abnormalities, including claw toes (33.3%), hammertoes (22.2%), and hallux abducto valgus (11.1%), than their healthy counterparts. Gait analysis results indicate a significant difference between the two groups at the hindfoot-to-tibia angle at heel strike and toe-off, suggesting limited ankle joint motion. CONCLUSIONS: Children with T1DM demonstrated a higher frequency of structural foot pathologies than did healthy children possibly associated with limited ankle sagittal plane movement. Screening is warranted to identify and manage these conditions early to reduce their risk of more significant foot problems associated with DM in adulthood.

A recessive PRDM13 mutation results in congenital hypogonadotropic hypogonadism and cerebellar hypoplasia.

The positive regulatory (PR) domain containing 13 (PRDM13) putative chromatin modifier and transcriptional regulator functions downstream of the transcription factor PTF1A, which controls GABAergic fate in the spinal cord and neurogenesis in the hypothalamus. Here, we report a recessive syndrome associated with PRDM13 mutation. Patients exhibited intellectual disability, ataxia with cerebellar hypoplasia, scoliosis, and delayed puberty with congenital hypogonadotropic hypogonadism (CHH). Expression studies revealed Prdm13/PRDM13 transcripts in the developing hypothalamus and cerebellum in mouse and human. An analysis of hypothalamus and cerebellum development in mice homozygous for a Prdm13 mutant allele revealed a significant reduction in the number of Kisspeptin (Kiss1) neurons in the hypothalamus and PAX2+ progenitors emerging from the cerebellar ventricular zone. The latter was accompanied by ectopic expression of the glutamatergic lineage marker TLX3. Prdm13-deficient mice displayed cerebellar hypoplasia and normal gonadal structure, but delayed pubertal onset. Together, these findings identify PRDM13 as a critical regulator of GABAergic cell fate in the cerebellum and of hypothalamic kisspeptin neuron development, providing a mechanistic explanation for the cooccurrence of CHH and cerebellar hypoplasia in this syndrome. To our knowledge, this is the first evidence linking disrupted PRDM13-mediated regulation of Kiss1 neurons to CHH in humans.