NUDT2 is an enzyme important for maintaining the intracellular level of the diadenosine tetraphosphate (Ap4A). Bi-allelic loss of function variants in NUDT2 has recently been reported as a rare cause of intellectual disability (ID). Herein, we describe a Chinese girl with ID, attention deficit hyperactivity disorder (ADHD), and motor delays with abnormal walking posture and difficulty climbing stairs, who bears compound heterozygous variants c.34 C > T (p.R12*) and c.194T > G (p.I65R) in NUDT2. Homozygous variants c.34 C > T (p.R12*) or c.186del (p.A63Qfs*3) in NUDT2 were previously reported to cause ID. This is the first patient with ID due to compound heterozygous variants in NUDT2 and p.I65R is a novel missense variant. This study enriched the genotype and phenotype of NUDT2-related ID and supported the critical developmental involvement of NUDT2.

Xia-Gibbs syndrome (XGS) is a recently discovered genetic disorder. It is characterized by global developmental delay, intellectual impairment, hypotonia, and sleep abnormalities. While the current literature emphasizes on the genotype and phenotype of this rare condition, it does not provide any description of the physiotherapy management of patients with XGS. We report a case of a 27-month-old Indian male diagnosed with XGS, who presented with difficulty in sitting without support. He had dysmorphic facies, hypotonia, hyperextensible joints, mild kyphoscoliosis, and global developmental delay. His parents and an elder female sibling were clinically asymptomatic. The physiotherapy intervention was based on the principles of neurodevelopmental treatment (NDT) and sensory integration (SI). The management included facilitation of transitions, weight-bearing exercises, wheelbarrow walking, joint compressions, rib cage mobilization, multidirectional reaching, and pushing-pulling activities along with the use of equipment like Swiss ball, balance board, stability disc, trampoline, swing system, walker (rollator), and walking harness. Also, stabilizing pressure input orthosis (SPIO) for the trunk and ankle-foot orthosis (AFO) followed by supramalleolar orthosis (SMO) were used for support. Thereafter, the child was able to stand and walk without support at the age of 36 months, and walk on uneven terrain at the age of 42 months. In addition, he could negotiate stairs using handrails with mild assistance. His gross motor function measure-88 (GMFM-88) total score improved from 21% at the presentation to 66.6% following the treatment. It was observed that the NDT and SI approaches along with the use of appropriate orthoses accelerated the achievement of motor milestones in this case. To the best of our knowledge, this is the first case report of a child with XGS that emphasizes on the course of physiotherapy management for the associated motor delay.

Cutis laxa is a set of genetically heterogeneous conditions with phenotypes ranging from progeria-like appearance, corneal clouding, clenched fingers with marked retardation of growth both pre and postnatal growth to very mild phenotypes with skin laxity becoming evident in 2nd or 3rd decade. A child who presents with predominant motor delay is written off with a clinical diagnosis of rickets in the absence of any clinical sign of lax skin. Here, we report a 2-year-old child who presented with motor delay and joint hyperlaxity. Mutation analysis demonstrated a heterozygous mutationc.G1867A in the exon 15 of ALDH18A1 gene known to cause autosomal dominant cutis laxa.