Generenetics

Dysmorphism: clue to metabolic disorders

Unveiling the molecular mechanisms responsible for disorders will lead to dysmorphic syndromes being understood as biochemical irregularities. An overview will be provided on how to recognize and classify dysmorphic features

Dysmorphic characteristics might not be noticeable at birth but could emerge gradually with age at different rates, seen in conditions like lysosomal storage disorders (mucopolysaccharidoses, oligosaccharidoses) or congenital disorders of glycosylation. However in certain metabolic defects, dysmorphic features can be noticed in new-born also for example Peroxisomal disorders (Zellweger syndrome), pyruvate dehydrogenase deficiency, cholesterol biosynthesis disorders (Smith-Lemli-Opitz syndrome), and multiple acyl-CoA dehydrogenase deficiency (glutaric aciduria type II)

PEROXISOMAL BIOGENESIS DISORDERS

peroxisomal biogenesis disorders are the continuum from severe Zellweger syndrome to milder phenotypes

     Zellweger syndrome.                Neonatal Adrenoleukodystrophy.               Infantile Refsum  disease

Zellweger syndrome:

features:Large fontanelles, Flat occiput Macrocephal, Posteriorly rotated ears, Upward slanting palpebral fissures Hypertelorism, High arched palate, Protruding tongue, Redundant skin folds of neck

 https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/zellweger-syndrome

 

https://www.healtheuropa.com/zellweger-spectrum-disorders/88667/

CHOLESTEROL SYNTHESIS DEFECTS:

Ex: Smith-lemli- Opitz syndrome (SLOS), Antley Bixler syndrome, Child syndrome

Smith-lemli- Opitz syndrome (SLOS),

Characteristic facial features includes narrow forehead, epicanthal folds, ptosis, short mandible with preservation of jaw width, short nose, anteverted nares, and low-set ears. 2-3 syndactyly of the toes, Microcephaly, Hypospadias in males, Cleft palate, Postaxial polydactyly

MUCOPOLYSACCHROIDOSIS

EX- Hurler syndrome, Hunter syndrome

Coarse features are diagnostic

Features that make face look coarse:

• Thick nasal tip and nostrils

• Prominent supraorbital ridges

• Frontal bossing

• Macrocephaly

• Hirsuitism

Nodular skin lesions are characteristics of MPSII

 https://doi.org/10.4103/2229-5178.198772 

https://www.researchgate.net/publication/5607595_Recognition_and_Diagnosis_of_Mucopolysaccharidosis_II_Hunter_Syndrome

CONGENITAL DISORDERS OF GLYCOSYLATION (CDG)

Not very specific phenotypes but they have broad forehead, strabismus, upslanted eyes, long fingers, lipodystrophy, wide mouth, inverted nipples, long philtrum and joint laxity

https://doi.org/10.1136/jmedgenet-2018-105588

 EYE FINDINGS: galactosemia (cataract), cystinosis (photophobia) Lowe syndrome (cong. Cataract & Glaucoma), and homocystinuria (subluxated lens)

KINKY HAIR : in Menkes disease.

SKIN FINDINGS: Fabry disease (Hypohidrosis, Angiokeratoma), Hunter syndrome (Pebbly skin lesions  ), steroid sulphatase deficiency (icthyosis)