Dubowitz syndrome Q87.0

Probable autosomal recessive inheritance.

Overall, the DubS-like clinical phenotype is associated with a large heterogeneity of gene loci. Genome-wide sequencing, filtering of rare variants, and computational and Mendelian genomic analysis resulted in a tentative molecular diagnosis in 13/27 (48%) families studied. The molecular diagnoses included:

• biallelic variants in the SKIV2L, SLC35C1, BRCA1, NSUN2 genes;
• de novo variants in the genes ARID1B, ARID1A, CREBBP, POGZ, TAF1, HDAC8
• and copy number variations in ARID1A (1p36.11), VPS13B (1p36.11), HDAC8 (Xp22 and Xq13 ) genes.

Only one gene, HDAC8, could explain the phenotype in more than one family (N = 2). (Dyment DA et al. 2021).

By 2021, just over 200 people had been diagnosed with Dubowitz syndrome or a "Dubowitz-like" condition.

Integument: Atopic dermatitis, dermatitic changes on the face and over the extensor surfaces of the large joints, usually improvement at the latest from the age of 4.

In isolated cases, a tendency to spontaceloids has been demonstrated (Paradisi M et al. 1994).

Extracutaneous manifestations: short stature, pre- and postnatal; delayed bone maturation, mental retardation (not obligate) and microcephaly, chronic rhinitis/otitis; in childhood, chronic diarrhea.

Rare: immunodeficiency, aplastic anemia, malignant lymphoma, acute lymphoblastic leukemia. Ptosis of upper eyelids, rarefaction of lateral eyebrows, hypertelorism, delayed eruption of teeth, susceptibility to caries, high palate, thinning hair, cleft palate, hypospadias, cryptorchidism, congenital heart defects, bifid thumb endphalanx, syndactyly between 2nd and 3rd toes.

Comprehensive allergological clarification, regular physical examinations and laboratory checks. Early diagnosis is important to recognize and treat rare life-threatening complications (e.g. aplastic anemia) in time.

Symptomatic therapy of eczematous skin lesions, e.g. prednicarbate in O/W as well as emulsions of type W/O several times a day, additionally 2 times/week refatting oil baths (e.g. Balneum Hermal, Linola fat oil bath).

Rhinoconjuctivitis allergica: Levocabastine (e.g. Livocab) eye drops or nasal spray.

1. Dubowitz V (1965) Familial low birthweigt dwarfism with an unusual facies and a skin eruption. J Med Genet 2: 12-17
2. Dyment DA et al (2021) Alternative genomic diagnoses for individuals with a clinical diagnosis of Dubowitz syndrome. Am J Med Genet A 185: 119-133.
3. Hansen KE et al (1995) Dubowitz syndrome - long-term follow-up of an original patient. Am J Med Genet 55: 161-164.
4. Lyonnet S, Schwartz G, Gatin G et al (1992) Blepharophimosis, eczema, and growth and developmental delay in a young adult: late features of Dubowitz syndrome? J Med Genet 29: 68-69
5. Oguz KK et al (2003) Cranial midline abnormalities in Dubowitz syndrome: MR imaging findings. Eur Radiol 13: 1056-1057
6. Opitz JM, Pfeiffer RA, Hermann JPR, Kushnick T (1973) Studies of malformation syndromes of man. XXIX B: The Dubowitz syndrome. Further observations. Z Kinderheilkd 116: 1-12
7. Paradisi M et al (1994) Dubowitz syndrome with keloidal lesions. Clin Exp Dermatol 19:425-427.
8. Vieluf D et al (1990) Dubowitz syndrome: atopic dermatitis, low birth weight, dwarfism and facial dysmorhism. Dermatologica 180: 247-249