Faculty Bibliography

Pontocerebellar hypoplasia type 9 (PCH9) is an autosomal recessive neurodevelopmental disorder caused by pathogenic variants in the AMPD2 gene. We evaluated the son of a consanguineous couple who presented with profound hypotonia and global developmental delay. Other features included sensorineural hearing loss, asymmetric astigmatism, and high myopia. Clinical whole-exome sequence analysis identified a homozygous missense variant in AMPD2 (NM_001257360.1:c.2201C > T, p.[Pro734Leu]) that has not been previously reported. Given the strong phenotypic overlap with PCH9, including the identification of the typical "Figure 8" appearance of the brainstem on neuroimaging, we suspect this variant was causative of the neurodevelopmental disability in this individual. An additional homozygous nonsense variant in COL11A1 (NM_001854.4:c.1168G > T, p.[Glu390Ter]) was identified. Variants in this alternatively spliced region of COL11A1 have been identified to cause an autosomal recessive form of Stickler syndrome type 2 characterized by sensorineural hearing loss and eye abnormalities, but without musculoskeletal abnormalities. The COL11A1 variant likely also contributed to the individual's phenotype, suggesting two potentially relevant genetic findings. This challenging case highlights the importance of detailed phenotypic characterization when interpreting whole exome data.

BACKGROUND: Children with medical complexity have a high prevalence of sleep disorders. However, outpatient polysomnography to evaluate for these conditions may be difficult to perform because of lack of skilled nursing care. The aim of this study was to explore polysomnography indications in hospitalized children and assess its impact on patient care. METHODS: Data from 85 inpatient polysomnographies of 70 children hospitalized between March and December 2014 were retrospectively collected. RESULTS: Sixty percent of patients were boys with ages 6.5 +/- 6 years. Chronic respiratory failure was present in 33.8%, airway obstruction due to defects of the tracheobronchial tree or craniofacial abnormalities in 54.3%, neurological complications of the perinatal period in 22.9%, genetic syndromes and neurodegenerative disorders in 31.4%, congenital myopathies in 5.7%, metabolic diseases in 4.3% and congenital cyanotic heart defects in 4.3%. Indications for polysomnography included assessment of chronic pulmonary disease (60%), ventilator requirements (41.2%), apnea/desaturation (23.5%), and acute life-threatening events (1.2%). Abnormal results were found in 89.4%. The observed diagnosis was obstructive sleep apnea in 64.7%, signs of chronic lung disease in 34.1%, hypoventilation in 9.4%, periodic breathing in 3.5%, and periodic limb movement of sleep in 4.7%. The following interventions were performed: adjustment of ventilator parameters (45.8%), positive airway pressure initiation (24.7%), otorhinolaryngology referral (30.6%), supraglottoplasty (2.4%), tracheostomy decannulation (2.4%), and tracheostomy placement (3.5%). Nine patients had available follow-up polysomnograms, all showing improvement in sleep variables after adherence to recommended interventions. CONCLUSIONS: In patients with medical complexity, inpatient polysomnographies give invaluable information to guide immediate medical decision making and should be strongly considered if resources allow this.

While inguinal hernia is common in the primary care office, the differential diagnosis is extensive and includes infectious, inflammatory and neoplastic processes. Varicocele is another frequent, generally benign condition which occasionally reflects serious disease entities. Left-sided or bilateral varicoceles account for the overwhelming majority of varicoceles because the left gonadal vein drains into the left renal vein in contrast to the right gonadal vein, which drains directly into the inferior vena cava, thus making left-sided or bilateral venous congestion more likely. Presence of an uncommon unilateral right-sided varicocele thus warrants further radiological workup, in particular CT abdomen and pelvis, to evaluate for retroperitoneal pathology. We describe a case in which appropriate use of a variety of imaging modalities including testicular ultrasound and CT led to an important diagnosis of a large, well-differentiated liposarcoma in the right retroperitoneum of a patient with a right-sided groin mass.