Adducted thumb syndrome

Adducted thumb syndrome recessive form, also known as Christian syndrome or Craniostenosis arthrogryposis cleft palate, is a rare disease affecting multiple systems causing malformations of the palate, thumbs, and upper limbs. The name Christian syndrome derives from Joe. C. Christian the first person to describe the condition. Christian-Andrews-Conneally-Muller syndrome is another term, named after the other authors (P. A. Andrews, P. M. Conneally and Jans Muller) of the original publication.^[1][2] It is an autosomal recessive connective tissue disorder characterized by congenital malformations, contractures of the thumb and feet, a typical facial appearance, and normal cognitive development. This is caused by mutation in the CHST14 (CARBOHYDRATE SULFOTRANSFERASE 14) gene^[3]

Medical description

This is an extremely rare syndrome of brain and respiratory tract malformations incompatible with life beyond a few months. Infants have microcephaly with craniostenosis and dysmyelination of the brain. The thumbs are adducted and do not extend during the Moro reflex. There may be generalized hypotonia, cleft palate (or at least a high arch), arthrogryposis, swallowing and breathing difficulties from respiratory tract malformations, hypertrichosis, and a myopathic stiff face.

Sample Cases

• Male and female cousins, the offspring of consanguineous Turkish parents, have been affected by a hitherto unreported combination of problems comprising moderate to severe psychomotor developmental delay, ocular anterior chamber abnormality, facial dysmorphisms (broad, bossed forehead, late-closing fontanelle, telecanthus, downslanting palpebral fissures, posteriorly rotated ears, downturned angles of mouth), arachnodactyly and distal arthrogryposis with severely adducted thumbs and club feet. This striking phenotype has some similarities with the multiple pterygium syndrome (Escobar syndrome), but it most likely represents a distinct condition caused by an autosomal recessive gene defect.^[4]
• A female newborn baby with a "myopathic" stiff face, open mouth, high-arched palate, microgenia, generalized muscular hypotonia, limited extension of elbows, wrists and knees, flexed adducted thumbs, velopharyngeal insufficiency, and hypertrichosis. Death occurred at 3 months due to respiratory insufficiency. Muscular biopsy revealed myopathic abnormalities.

Genetics

The disease was documented in 1971 by Dr. Joe Christian and three associates after examining three Amish siblings.^[5] Evidence for autosomal recessive inheritance comes from three Amish sibships whose parents all shared a common ancestor. No genomic studies have been done on these families. The relationship of this disorder to the X-linked MASA syndrome (#303350), another adducted thumb disorder, is unknown. Respiratory disease and CNS dysmyelination are not part of the MASA syndrome which seems to be a form of spastic paraplegia with less severe neurological signs than found in the Amish cases.^[6]

Adducted thumb syndrome has an autosomal recessive pattern of inheritance.

All six parents shared a common ancestral couple, making this a possible issue with consanguinity.^[7] Inheritance is believed to be autosomal recessive,^[7] caused by mutation in the CHST14 (carbohydrate sulfotransferase 14) gene.^[8]

Signs and symptoms

This syndrome is characterized by typical facial appearance, slight build, thin and translucent skin, severely adducted thumbs, Arachnodactyly (a condition in which the fingers are long and slender and curved. It appears as spider legs), clubfeet, joint instability, facial clefting, and bleeding disorders, as well as heart, kidney, or intestinal defects. Severe psychomotor and developmental delay and decreased muscle tone may also be present during infancy. Cognitive development during childhood is normal.^[9]

Diagnosis

This syndrome is associated with microcephaly, arthrogryposis, and cleft palate and various craniofacial, respiratory, neurological, and limb abnormalities, including bone and joint defects of the upper limbs, adducted thumbs, camptodactyly, and talipes equinovarus or calcaneovalgus. Patients with the disease are considered intellectual disability, and most die in childhood. Patients often suffer from respiratory difficulties, such as pneumonia, and from seizures due to dysmyelination in the white matter.^[10] It has been hypothesized that the Moro reflex (startle reflex in infants) may be a tool in detecting the congenital clapsed thumb early in infancy.^[11] The thumb will normally extend as a result of this reflex.

Recessive form

• Symptoms

Small head, Premature fusion of skull bones, Arthryogryposis, Cleft palate, Craniofacial abnormalities

• Diagnosis

This syndrome is associated with microcephaly, arthrogryposis, and cleft palate and various craniofacial, respiratory, neurological, and limb abnormalities, including bone and joint defects of the upper limbs, adducted thumbs, camptodactyly, and talipes equinovarus or calcaneovalgus. Patients with the disease are considered intellectual disability, and most die in childhood. Patients often suffer from respiratory difficulties, such as pneumonia, and from seizures due to dysmyelination in the white matter.It has been hypothesized that the Moro reflex (startle reflex in infants) may be a tool in detecting the congenital clapsed thumb early in infancy. The thumb will normally extend as a result of this reflex.^[12]

Specialist and specialty centers

• Neurologist
• Pulmonologist
• Pediatrician

Relations

• BACKGROUND:

MASA syndrome is the acronym for Intellectual disability, Aphasia, Shuffling gait and Adducted thumbs. Linkage studies have shown linkage to markers in the Xq28 band.

• CASE REPORTS:

Case no. 1: Mickaël was examined at the age of 3 yr 4 mo. He was intellectual disability (IQ = 40), aphasic, and had spastic gait, moderate facial dysmorphy and adducted thumbs. His parents were normal, except that his mother had similar facial dysmorphy. His brain CT scan was normal. Case no. 2: Philippe was the elder brother of Mickaël. When examined at the age of 5 years, he had the same features as his brother. His IQ was 40. His brain-CT scan was also normal. DNA analysis with markers for the Xq28 area showed that the brothers had received different X chromosomes from their mother.

• CONCLUSION:

DNA studies suggest that the MASA syndrome is heterogeneous^[13]

See also

• Tetrasomy 18p

References

External links

• Whonamedit.com entry on Christian syndrome