1 - Serviço de Genética Médica, Hospital Dona Estefânia – Centro Hospitalar Lisboa Central, Lisboa, Portugal
2 - Consulta de Genética Médica, Hospital dos Lusíadas, Lisboa, Portugal
- Comunicação oral - EuroDysmorpho, 33rd Annual Meeting of European Dysmorphology, 13-16 de setembro 2023, Lisboa
A 19-years-old male was first referred to our outpatient genetic department at the age of 16-month-old with global development delay, epilepsy and hypotonia. He is the only child of non-consanguineous parents with no relevant family history. Pregnancy was unremarkable. The patient was born at 40 weeks of gestation without complications and with adequate birthweight, length and cephalic perimeter for gestational age. He had an unremarkable neonatal period. At 6-months-old, he presented with epilepsy, hypotonia and motor development delay. Brain magnetic resonance imaging identified ventriculomegaly and electroencephalography irregular activity. Subsequently, at our observation, he showed broad forehead, strabismus, epicantus, long philtrum, joint laxity and cryptorchidism. In the first 3 years of age, he had several hospital admissions as result of decompensation of epilepsy and upper respiratory infections. From the age of 3-years-old, he remained epilepsy-free. In addition, he revealed a progressive global developmental delay with moderate cognitive impairment (global IQ of 43). At 13-years-old, he presented with pulmonary hypertension. A patent foramen ovale was the only finding in the echocardiogram. A transcatheter closure was performed, targeted medical treatment was initiated and since then the patient remains asymptomatic. Throughout the years, he showed progressive coarse facial features. At last evaluation by the age of 19 years, facial dysmorphims became more evident such as long face, bitemporal narrowing, pear-shaped nose, open mouth, thick inferior lip, prominent incisors, small hypothenar eminence with tapering fingers, lumbar hyperlordosis, and bilateral sandal gap. The patient’s neurologic condition remains stable. Extensive metabolic investigation, karyotype, FRAXA study, and MS-MLPA assay for the 15q11-q13 region were normal. Chromosomal microarray identified a heterozygous deletion encompassing NRXN1 classified as likely pathogenic, inherited from a healthy father. However, this finding does not seem to fully explain our patient’s phenotype. Due to the patient’s phenotype, we suspected of a BAFopathy but clinical exome was inconclusive, without any variant of interest in these genes. This case remains without a conclusive molecular diagnosis that could offer an appropriated genetic counselling and a better surveillance to this patient and family. By presenting this case, we hope that this discussion can bring us one-step closer to a possible molecular diagnosis.
Palavras Chave: Developmental delay, epilepsy, unknown diagnosis