Comorbidities in children with cerebral palsy: a single-centre cross-sectional hospital-based study from India.

OBJECTIVE: To describe the comorbidities in children with cerebral palsy (CP) and determine the characteristics associated with different impairments. DESIGN: Cross-sectional study. SETTING: Tertiary care referral centre in India. PATIENTS: Between April 2018 and May 2022, all children aged 2-18 years with a confirmed diagnosis of CP were enrolled by systematic random sampling. Data on antenatal, birth and postnatal risk factors, clinical evaluation and investigations (neuroimaging and genetic/metabolic workup) were recorded. MAIN OUTCOME MEASURES: Prevalence of the co-occurring impairments was determined using clinical evaluation or investigations as indicated. RESULTS: Of the 436 children screened, 384 participated (spastic CP=214 (55.7%) (spastic hemiplegic=52 (13.5%); spastic diplegia=70 (18.2%); spastic quadriplegia=92 (24%)), dyskinetic CP=58 (15.1%) and mixed CP=110 (28.6%)). A primary antenatal/perinatal/neonatal and postneonatal risk factor was identified in 32 (8.3%), 320 (83.3%) and 26 (6.8%) patients, respectively. Prevalent comorbidities (the test used) included visual impairment (clinical assessment and visual evoked potential)=357/383(93.2%), hearing impairment (brainstem-evoked response audiometry)=113 (30%), no understanding of any communication (MacArthur Communicative Development Inventory)=137 (36%), cognitive impairment (Vineland scale of social maturity)=341 (88.8%), severe gastrointestinal dysfunction (clinical evaluation/interview)=90 (23%), significant pain (non-communicating children's pain checklist)=230 (60%), epilepsy=245 (64%), drug-resistant epilepsy=163 (42.4%), sleep impairment (Children's Sleep Habits Questionnaire)=176/290(60.7%) and behavioural abnormalities (Childhood behaviour checklist)=165 (43%). Overall, hemiparetic and diplegic CP and Gross Motor Function Classification System ≤3 were predictive of lesser co-occurring impairment. CONCLUSION: CP children have a high burden of comorbidities, which increase with increasing functional impairment. This calls for urgent actions to prioritise opportunities to prevent risk factors associated with CP and organise existing resources to identify and manage co-occurring impairments. TRIAL REGISTRATION NUMBER: CTRI/2018/07/014819.

Clinical and molecular spectrum associated with Polymerase-γ related disorders.

BACKGROUND: POLG pathogenic variants are the commonest single-gene cause of inherited mitochondrial disease. However, the data on clinicogenetic associations in POLG-related disorders are sparse. This study maps the clinicogenetic spectrum of POLG-related disorders in the pediatric population. METHODS: Individuals were recruited across 6 centers in India. Children diagnosed between January 2015 and August 2020 with pathogenic or likely pathogenic POLG variants and age of onset <15 years were eligible. Phenotypically, patients were categorized into Alpers-Huttenlocher syndrome; myocerebrohepatopathy syndrome; myoclonic epilepsy, myopathy, and sensory ataxia; ataxia-neuropathy spectrum; Leigh disease; and autosomal dominant / recessive progressive external ophthalmoplegia. RESULTS: A total of 3729 genetic reports and 4256 hospital records were screened. Twenty-two patients with pathogenic variants were included. Phenotypically, patients were classifiable into Alpers-Huttenlocher syndrome (8/22; 36.4%), progressive external ophthalmoplegia (8/22; 36.4%), Leigh disease (2/22; 9.1%), ataxia-neuropathy spectrum (2/22; 9.1%), and unclassified (2/22; 9.1%). The prominent clinical manifestations included developmental delay (n = 14; 63.7%), neuroregression (n = 14; 63.7%), encephalopathy (n = 11; 50%), epilepsy (n = 11; 50%), ophthalmoplegia (n = 8; 36.4%), and liver dysfunction (n = 8; 36.4%). Forty-four pathogenic variants were identified at 13 loci, and these were clustered at exonuclease (18/44; 40.9%), linker (13/44; 29.5%), polymerase (10/44; 22.7%), and N-terminal domains (3/44; 6.8%). Genotype-phenotype analysis suggested that serious outcomes including neuroregression (odds ratio [OR] 11, 95% CI 2.5, 41), epilepsy (OR 9, 95% CI 2.4, 39), encephalopathy (OR 5.7, 95% CI 1.4, 19), and hepatic dysfunction (OR 4.6, 95% CI 21.3, 15) were associated with at least 1 variant involving linker or polymerase domain. CONCLUSIONS: We describe the clinical subgroups and their associations with different POLG domains. These can aid in the development of follow-up and management strategies of presymptomatic individuals.

Acute lymphoblastic leukemia with treatment--naive Fanconi anemia.

Fanconi anemia is known to have a predisposition to cancer, mostly associated with acute myeloid leukemia. We report an eight year old girl with treatment and naive FA who developed acute lymphoblastic leukemia. She was initiated on chemotherapy but she failed to respond to treatment and died during induction phase of chemotherapy. While this association may be coincidental but possibility of transition of Fanconi anemia to ALL should be considered in view of high predisposition to cancer in this disorder.

A case of 9p deletion syndrome with Duane retraction syndrome.

The chromosome 9p deletion syndrome is a rare but specific clinical event. The clinical manifestations include dysmorphic facial features (trigonocephaly, midface hypoplasia, upward slanting palpebral fissures, and a long philtrum) and psychomotor retardation. Here we report a child with chromosome 9p deletion with Duane retraction syndrome, which has never been reported in the literature before.