Full Term male transferred to Nicklaus Children’s Hospital’s neonatal intensive care unit (NICU) at one week of age for concerns of an underlying genetic etiology given dysmorphic features, respiratory insufficiency and feeding difficulties. He was born via C-section from a pregnancy complicated by intrauterine growth restriction (IUGR) and clubfeet identified on second trimester ultrasound. At birth, he was noted to be small for gestational age (SGA) (birth weight near 2^nd percentile) and to have a wide posterior fontanelle, down slanting palpebral fissures, micrognathia with limited mouth opening; bilateral cryptorchidism; arthrogryposis multiplex congenita (flexion deformity of wrists and proximal metacarpophalangeal joints and bilateral talipes equinovarus); bilateral club feet; Mongolian spot on the right buttock; hypertonia of upper and lower extremities; weak suck and gag reflexes and; absent rooting and Moro reflexes. Perinatal course was complicated by feeding difficulties with nasogastric tube (NG tube) dependence, respiratory distress requiring invasive respiratory support, apneic episodes and hypoglycemia requiring treatment with dioxide.

Chest and abdominal x-rays, abdominal ultrasound, and echocardiogram were reported as normal. Bone survey demonstrated findings consistent with arthrogryposis, bilateral clubfeet, and eleven ribs. CT scan of the face revealed a hypoplastic mandible, flattening of the condylar heads, and bilaterally shallow temporomandibular joint glenoid fossa.

Botox injection was performed to help manage oral secretions at 1 month of age. Subperiosteal release of the mouth floor was performed at 1 month of age to help with oral feeding and respiration. The patient failed extubation after the release of the mouth floor. Due to high risk for aspiration and continued respiratory issues, gastrostomy tube (G-tube) with fundoplication and tracheostomy were performed at 6 weeks of life.

In addition to the feeding and respiratory issues, there was suspicion of partial diabetes insipidus due to persistent hypernatremia and low urine osmolarityand specific gravity. Brain MRI showed suspicion of ectopic neurohypophysis but was otherwise normal. The patient also had episodes of hypoglycemia requiring continuous feeds and treatment with diazoxide. Insulin, growth hormone, free fatty acids, cortisol, and β-hydroxybutyrate random levels were unremarkable, although a critical sample was unable to be collected during hypoglycemic events.

Initial genetic work-up included normal chromosome analysis, chromosome microarray, spinal muscular atrophy analysis, and Fragile X testing. The patient and both of his parents were then enrolled in the protocol for rapid whole genome sequencing (rWGS).