Ichthyosis and erythrokeratoderma

Gene: MPDU1

Green List (high evidence)

Comment on list classification: There are more than 3 unrelated individuals reported in literature with biallelic MPDU1 variants and syndromic ichthyosis / erythrokeratoderma. Hence, this gene should be promoted to Green at the next update, with MOI set to BIALLELIC, autosomal or pseudoautosomal.

Created: 26 Mar 2026, 3:26 p.m. | Last Modified: 26 Mar 2026, 3:26 p.m.

Panel Version: 4.10

PMID: 11733564 Schenk et al., 2001
Patient L admitted to hospital at the age of 5 months for attacks of hypertonia, a congenital disabling ichthyosis-like skin disorder and psychomotor retardation. Skin biopsy showed unspecific changes. At 16yo, she had severe dwarfism, psychomotor retardation (developmental level of 1 year), and unchanged skin disease. She was compound het for MPDU1 variants: c.2T>C, p.Met1Thr & c.356T>C, Leu119Pro.

PMID: 29721919 Thiel et al., 2018
Turkish girl with a homozygous MPDU1 variant c.218G>A, p.Gly73Glu. Method: exome + Sanger seq. She presented with hypotonia, facial dysmorphism, microcephaly, severe ichthyosis, and developmental delay. She also had severe non-compaction cardiomyopathy. Older brother similarly affected.

PMID: 35279850 Abu Bakar et al., 2022
2 patients homozygous for c.69del, p.(Tyr23*) and 2 homozygous for c.532_534del, p.(His178del). All 4 patients had seizures, ID, hypotonia. Skin wise, 2 patients had infiltrated and dry skin, universal hirsutism, one had seborrhoea on scalp.

PMID: 36755425 Darouich et al., 2023
Female infant with novel homozygous missense variant NM_004870.4(MPDU1):c.503G>A/p.Gly168Glu. She presented with symmetric growth restriction, facial dysmorphism, ichthyosis, hepatomegaly with severe duct plate malformation, renal cortical tubular and glomerular cysts, moderate cerebral tetraventricular dilatation, and severe pontocerebellar hypoplasia.

PMID: 38831602 Wei et al., 2025
10 yo boy, presented with erythrokeratodermia variabilis at birth (mostly hands and feet affected). He also exhibited seizures, ID and esotropia. No abnormalities of hair, teeth of nails noted. He was compound het for c.262G>A, p.Gly88Arg & c.660_662del, p.Ser221del.

Created: 26 Mar 2026, 3:24 p.m. | Last Modified: 26 Mar 2026, 3:24 p.m.

Panel Version: 4.9

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital disorder of glycosylation, type If, OMIM:609180

Publications

• 11733564
• 29721919
• 35279850
• 36755425
• 38831602

Green List (high evidence)

Sources: Literature

Created: 10 Mar 2026, 9:15 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ichthyosis

Publications

• 11733556