Homozygous Pathogenic Variant in Elongation Factor-Like 1 (EFL1) as a Causal Factor in Shwachman-Diamond Syndrome 2...

Shwachman-Diamond syndrome type 2 (SDS2) is a rare ribosomopathy caused by biallelic mutations in the EFL1 gene. This condition presents with features similar to classic SDS1 such as pancreatic insufficiency and haematologic abnormalities.

We report a Palestinian female infant admitted to the NICU at H-Clinic Hospital, Ramallah, in January 2023, with a homozygous mutation in the EFL1 gene (c.3284G>A; p.Arg1095Gln), identified through whole exome sequencing and confirmed by Sanger sequencing. In addition to typical SDS2 features-pancytopenia, pancreatic insufficiency and growth failure-the patient exhibited unique manifestations, including ROP-like retinal changes, infantile esotropia with inferior oblique overaction, and elevated ACTH and 17-hydroxyprogesterone levels, indicating adrenal dysfunction.

These findings expand the SDS2 phenotype to include novel ocular and endocrine involvement. No other pathogenic variants were identified by bioinformatic analysis. The recurrence of this variant in unrelated Palestinian families suggests a possible founder effect.

This case underscores the importance of extended genetic testing and multidisciplinary evaluation in rare syndromes. It highlights the need for broader awareness of SDS2 among endocrinologists and ophthalmologists due to the novel clinical manifestations observed.