Abstract 42: A case of skeletal dysplasia

Introduction: Dyggve-Melchior-Clausen syndrome (DMC) is a rare, progressive genetic disorder characterized by abnormal skeletal development, microcephaly and intellectual disability. It involves mutation of Dymeclin (DYM) gene on chromosome 18q12.1 that encodes for DYM protein which is expressed in cartilage, bone, and brain. Case Discussion: Child aged 9 years with complains of failure to gain height-since infancy with intellectual disability. Child developed generalized joint pains since-4 years. Born as the first child to a second-degree consanguineous marriage. Oligohydramnios was diagnosed in second trimester and was delivered at 34 weeks by LSCS due to PPROM. Birth weight was 2 kg and APGAR was 9. Developmental milestones were delayed. Child has impaired speech and behavioral abnormalities like aggressive behavior, self harming tendencies, hyperactivity, poor attention span and temper tantrums. Younger sibling expired at the age of 3 months due to recurrent vomiting and seizures. Anthropometry showed height of117 cm (Ht SDS -2.09) and weight of 24 kg (25-50 percentile). US/LSratio-1.02, Arm span-119.5 cm, Head circumference-48.8 cm (-2SDS), Mid-parental height unable to assess as father is abroad. There was short forehead, flat occiput, large ears, poor dental hygiene, deformities of hands, widened wrists, short broad fingers, knock knees and widened ankle joint. Spinal examination showed kyphosis in upper back, exaggerated lordosis in lower back. Gait was of waddling nature. Laboratory evaluation showed hemogram was within normal limits. Calcium-9.9 mg/dl. Phosphorus-4.9 mg/dl, Alkaline phosphatase-299 IU. Creatinine-0.34 mg/dl.TT3-1.70 ng/ml, TT4-4.7 m/dl, TSH-1.56 mIU/ml. VIT D—29.12 ng/ml, S.PTH—38.2 pg/ml. C spine Xray suggestive of atlantoaxial dislocation. Thoraco-lumbo-sacral spine showed decreased vertebral body height, central notching and beaking of superior and inferior end plates. Hand x ray showed small metacarpals and enlarged epiphysis of distal radius and ulna. Pelvic Xray showed bilateral small iliac wing, lacy appearance of iliac crests, multiple small translucent areas in pelvic rami, symmetric enlargement of femoral heads on lateral aspect and displaced laterally. Leg Xray showed enlarged medial epiphysis of distal femur, tibia and irregularities of metaphyses. Karyotyping-46XY. Genetic analyses revealed homozygous mutation of DYM gene on exon7 of chromosome 18–autosomal recessive suggestive of DYGGVE MELCHIOR CLAUSEN DISEASE. Mother had a pericentric inversion of chromosome 9. Conclusion: This is a rare case of Dyggve Melchior-Clausen syndrome with typical features of skeletal dysplasias and intellectual disability. Patient is being planned for atlanto-axial stabilisation surgery. Genetic counselling given to parents.