IllnessFrontonasal dysplasia + Opitz GBBB syndrome, differential diagnosis

NGS +

(Cranio)frontonasal dysplasia exhibits at least two of the following features: Hypertelorism, broad nose, nasal cleft(s) without nasal tip, facial cleft formation involving the nose, upper lip or palate or an anterior cranium bifidum occultum. Other features may include additional facial malformations, absence or malformed corpus callosum and intellectual deficit. At least three types of frontonasal dysplasia are distinguished by genetics and symptomatology. Frontonasal dysplasia 1 typically shows a long philtrum and ptosis. Frontonasal dysplasia 2 may have alopecia and enlarged parietal foramina, and boys with this form often have genital abnormalities. Frontonasal dysplasia 3 includes anophthalmia/ microphthalmia and low-set, retroverted ears as well as other most severe facial malformations. Life expectancy depends on the severity of the malformations.

Opitz G/BBB syndrome also shows abnormalities along the midline of the body. The two forms of Opitz G/BBB syndrome differ in their genetic causes. The common symptoms include hypertelorism, ENT and genital abnormalities, mild intellectual disability and developmental delay (50%), cleft lip with or without cleft palate, and special facial features that vary even within the same family. All classical hereditary patterns occur in the gene group to be differentially diagnosed, and the diagnostic yield by molecular genetics has not yet been more precisely determined.

Reference: https://rarediseases.org/rare-diseases/craniofrontonasal-dysplasia/

https://www.ncbi.nlm.nih.gov/books/NBK1327/

• Alias: Oblique facial clefting-1
• DD: DiGeorge or chromosome 22q11.2 deletion syndrome
• DD: Shprinzen or velocardiofacial syndrome
• Alias: Acromelic frontonasal dysostosis
• Alias: Craniofrontonasal dysplasia (as subgroup of Median cleft face syndrome)
• Allelic: Cardiac valvular dysplasia, XL (FLNA)
• Allelic: Congenital short bowel syndrome (FLNA)
• Allelic: Heterotopia, periventricular, 1 (FLNA)
• Allelic: Intestinal pseudoobstruction, neuronal (FLNA)
• Allelic: Mental retardation, with/-out nystagmus (CASK)
• Allelic: Terminal osseous dysplasia ((FFLNA)
• FG syndrome 2 (FLNA)
• FG syndrome 4 (CASK)
• Facial clefting, oblique, 1 (SPECC1L)
• Frontometaphyseal dysplasia 1 (FLNA)
• Frontonasal dysplasia 1 (ALX3)
• Frontonasal dysplasia 2 (ALX4)
• Frontonasal dysplasia 3 (ALX1)
• Hypertelorism, Teebi type (SPECC1L)
• Lujan-Fryns syndrome (MED12)
• Melnick-Needles syndrome (FLNA)
• Mental retardation + microcephaly with pontine + cerebellar hypoplasia (CASK)
• Ohdo syndrome, XL (MED12)
• Opitz GBBB syndrome, type I; Hypertelorism-hypospadias syndrome (MID1)
• Opitz GBBB syndrome, type II (SPECC1L)
• Opitz-Kaveggia syndrome (MED12)
• Otopalatodigital syndrome, type I (FLNA)
• Otopalatodigital syndrome, type II (FLNA)