IllnessUNC80 deficiency: Hypotonia-absent speech-cognitive developmental deleay; differential diagnosis

NGS +

UNC80 deficiency is a severe disorder characterized by disturbances of the nervous system and development from birth or early infancy. The patients have marked mental retardation, muscular hypotonia with hypertonia in the arms and legs. Speech is often absent, while seizures, nystagmus, strabismus and high-pitched screaming may occur. Affected individuals are of normal size at birth but grow slowly in infancy and childhood. Striking facial features vary in affected individuals with brachycephaly, triangular face shape with bar forehead, ptosis, epicanthus, outward down ward slanting palpebral fissures, short philtrum, open mouth and low-set ears. In addition, a short neck, scoliosis, contractures and clubfeet are observed. UNC80 deficiency is inherited in an autosomal recessive manner and results in impaired sodium transport with impaired generation and transmission of electrical signals. UNC80 not only forms part of the structure of the NALCN channelosome, but also stabilizes it in the neuronal membrane. The NALCN channelosome is critical for the excitability of neurons. The DNA diagnostic yield is unknown for this extremely rare disorder.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK453434/

• Alias: Hypotonia-speech impairment-severe cognitive delay syndrome (UNC80)
• Alias: Infantile Hypotonie mit psychomotorischer Retardierung + charakteristischem Gesicht (UNC80)
• Alias: Infantile hypotonia-psychomotor retardation-characteristic facies syndrome (UNC80)
• Alias: UNC80 deficiency
• Allelic: Autism susceptibility, XL 3 (UNC80)
• Allelic: Rett syndrome, preserved speech variant (MECP2)
• Allelic: Schizophrenia 15 (SHANK3)
• Angelman syndrome (UBE3A)
• Congenital contractures of the limbs + face, hypotonia + developmental delay (NALCN)
• Encephalopathy, neonatal severe (MECP2)
• Glass syndrome: ID, dysmorphic face, microgn., downsl. palp. fiss., cleft palate, many teeth (SATB2)
• Hypotonia, infantile, with psychomotor retardation + characteristic facies 1 (NALCN)
• Hypotonia, infantile, with psychomotor retardation + characteristic facies 2 (UNC80)
• Hypotonia, infantile, with psychomotor retardation, characteristic facies 3 (TBCK)
• Intellectual developmental disorder, XL syndromic, Lubs type (MECP2)
• Intellectual developmental disorder, XL, syndromic 13 (MECP2)
• Phelan-McDermid syndrome (SHANK3)
• Rett syndrome (MECP2)
• Rett syndrome, atypical (MECP2)