ESPE Abstracts

Background: Schaaf-Yang syndrome is caused by heterozygous mutation in the MAGEL2 gene (605283) on chromosome 15q11. Schaaf-Yang Syndrome is an autosomal dominant multisystem disorder characterized by psychomotor and mental retardation, hypotension, and behavioral abnormalities. Additional signs include joint contractures, feeding difficulties and various dysmorphic features. The severity of the disorder varies greatly: some patients may live with moderate disability. Individual lesions occur only if the mutation occurs in the paternal allele, since MAGEL2 is a gene imprinted on the mother. Here we report a case of Schaaf-Yang Syndrome with endocrine features.

Case report. Manifestation was at birth. A boy appeared to have disproportionately small hands and feet, dysmorphic facial features, esotropia and micrognathia. The patient was lethargic with no interest in feedings and poor suck/gag reflex. He was placed on feeds through a nasogastric tube. His laboratory workup was significant for hypoglycemia and hypocalcemia. On the first day of life, an MRI showed Grade I intraventricular hemorrhage bilaterally and a hemorrhage within the pituitary gland. His EEG showed bitemporal sharps and complexes concerning for subclinical seizures. At the age of 3 months boy had feeding difficulties with poor suck, muscle hypotonia, vomiting, failure to thrive, spasticity, generalized seizures, encephalopathy, optic atrophy, pachygyria, bulbar syndrome, congenital malformations of the osteoarticular system, camptodactyly, abnormal urinary system and external genitalia, hypogonadism.

His parents are non-consanguineous and asymptomatic. They have no further affected child. Laboratory; hypoglycemia: serum glucose 2.3 – 2.9 mmol/l, C-peptide 0.41 – 0.44 ng/ml (0.7 – 1.9). HbA1c - 4.6% insulin – 7,02 mcU/ml (2,0 – 25,0). TSH – 3.27 mIU/L, FT4 – 16.67 pmol/L, FT3 – 4.77 pmol/L, IGF-1/IGF-BP3 - normal, PTH – 38.58 pg/ml (15-68). screening for other endocrine dysfunctions was negative. Blood calcium – 2.48, ionized calcium – 1.21, phosphorus – 1.84 mmol/l. Total VitD (D2+D3) – 48,84 ng/ml (sufficient level 30 – 80). Total protein – 63 g/l. Ammoniak – 23.0 mol/l (15-70). Uric acid – increase. IgA anti-tissue transglutaminase antibodies – normal level, gliadin - 0.10 kU/L, kasein DPC – 0.31 kU/I. Zink – 15.3 mcmol/L (9.8 – 16.8), iron – 13.81 mcmol/L, magnesium – 1.0 mmol/L, copper level – 11.3 mcmol/l (10-22). Folic acid – 45.4 nmol/L (10.4 – 42.4). The genetic diagnosis of Schaaf-Yang syndrome is confirmed: MAGEL2 (NM-019066.4, sequencing, heterozygous variant c.1996dup p.(Gln666Profs*47).

Conclusion: Given the seriousness of the results, we strive to describe the early abnormalities in the endocrine status of a child with the unique phenotypic features of the MAGEL2 mutation, which determine clinical suspicion and early intervention to manage its complex manifestation.