Case report of rare neurodevelopmental Menke–Hennekam Syndrome

Abstract

Background: Menke–Hennekam Syndrome (MHS) is rare genetic multiple congenital anomalies/dysmorphic disorder characterized by variable intellectual disability, developmental delay, autistic behaviour, short stature, and microcephaly. MHS type 1 is caused by missense variants of CREBBP gene, located in exons 30 or 31 and it is allelic disorder for Rubinstein–Taybi syndrome. Methods: The proband is 7-year-old female who was born at 39 weeks of gestation from normal pregnancy, birth weight 2495 g (<3‰), birth hight 48 cm. Her mother received growth hormone during adolescence. Global developmental delay was noticed in the first year of life. At 5 years of age, she was assessed by scale of Diagnostic inventory for screening children, 1984 (DISC). Test value was 38-61%. Later, she had learning disabilities and special school needs. Paediatric endocrinologist assessed her for short stature multiple times and growth hormone deficiency diagnosis was rejected. At 4 years of age sleep EEG showed bilateral frontotemporal epileptic activity and epilepsy diagnosis was made. Dysmorphic facial features were noticed: strabismus, short and upslanted palpebral fissures, telecantus, depressed nasal ridge, short nose, anteverted nares, short columella, and long philtrum. Result: Whole exome sequencing (WES) showed likely pathogenic missense variant in CREBBP (NM_004380.3) gene c.5128T>C (p.Cys1710Arg) (PP3 strong, PM1 moderate, PM2 moderate, PP2 supporting) in the 30th exon. Only the mother was available for genetic testing and she was negative for the variant. Conclusions: The proband’s phenotype and genotype was compatible with diagnosis of rare neurodevelopmental Menke–Hennekam Syndrome. Appropriate genetic counselling was provided.