Clinical Presentation and Diagnosis of Smith-Lemli-Opitz Syndrome: First Case Report from Sudan

Abstract

Background: Smith-Lemli-Opitz syndrome (SLOS) is a congenital autosomal recessive disorder characterized by defective cholesterol metabolism, attributable to a deficiency of the enzyme 7-dehydrocholesterol reductase (DHCR7) caused by mutations in the DHCR7 gene maps to chromosome 11q13. SLOS is linked to a wide variety of congenital anomalies, failure to thrive, dysmorphological features, and intellectual disabilities caused by cholesterol metabolic abnormalities. Case Report: A 58-day-old Sudanese infant, the third offspring of parents in a consanguineous marriage, was brought to the hospital due to failure to thrive and delayed growth. Clinical examination revealed stunted growth, hypotonia, microcephaly, distinctive facial dysmorphism characterized by a broad nasal tip with anteverted nostrils and micrognathia, post-axial polydactyly in both upper and lower extremities, and ambiguous genitalia. A biochemical analysis revealed decreased plasma cholesterol levels alongside an increase in 7-dehydrocholesterol (7-DHC) concentration. The echocardiographic evaluation confirmed the presence of an atrial septal defect (ASD) while karyotyping demonstrated a normal male chromosomal pattern (46, XY). Based on these findings, a diagnosis of SLOS was made. Following thorough genetic counseling with the parents, the patient was referred to a pediatric tertiary care center for advanced management and continuous monitoring. Conclusion: Clinical presentation of SLOS cases can widely vary, from minor dysmorphic features to severe congenital and mental anomalies which may lead to miscarriage, so a high index of suspicion is required to expedite referral and diagnosis using available, affordable, specific biochemical, genetic testing, especially in limited health resources areas, where expensive molecular investigations are not available. Early diagnosis and effective genetic counseling may help to minimize comorbidity and enhance the quality of life for the whole family.

Keywords

• Smith-Lemli-Opitz syndrome
• SLOS
• ambiguous genitalia
• chromosomal analysis