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Birk-Barel syndrome(BIBARS)

MedGen UID:
393583
Concept ID:
C2676770
Disease or Syndrome
Synonyms: Birk Barel mental retardation dysmorphism syndrome; Mental retardation with hypotonia and facial dysmorphism
SNOMED CT: Intellectual disability, hypotonia, facial dysmorphism syndrome (764861005); Intellectual disability Birk-Barel type (764861005); Birk Barel mental retardation dysmorphism syndrome (764861005); KCNK9 (potassium two pore domain channel subfamily K member 9) imprinting syndrome (764861005)
 
Gene (location): KCNK9 (8q24.3)
 
Monarch Initiative: MONDO:0012856
OMIM®: 612292
Orphanet: ORPHA166108

Disease characteristics

Excerpted from the GeneReview: KCNK9 Imprinting Syndrome
KCNK9 imprinting syndrome is characterized by congenital central hypotonia (manifest as decreased movement, lethargy, and weak cry), severe feeding difficulties (resulting from facial weakness and poor suck), delayed development/intellectual disability, and dysmorphic manifestations. Poor feeding can cause failure to thrive during infancy unless managed appropriately. Significant dysphagia of solid foods typically persists until puberty. Intellectual disability can be severe. To date 19 individuals with a molecularly confirmed diagnosis have been reported. [from GeneReviews]
Authors:
Neda Zadeh  |  John M Graham   view full author information

Additional descriptions

From OMIM
Birk-Barel syndrome (BIBARS) is a paternally imprinted, autosomal dominant disorder characterized by motor and speech delay, impaired intellectual development, early feeding difficulties, muscular hypotonia, and behavioral abnormalities, including hyperactivity and aggression (summary by Cousin et al., 2022).  http://www.omim.org/entry/612292
From MedlinePlus Genetics
KCNK9 imprinting syndrome is a rare condition characterized by weak muscle tone (hypotonia) from birth. As a result, affected infants have a lack of energy (lethargy), a weak cry, and they move less than normal. Facial weakness and a poor ability to suck cause feeding difficulties, which can lead to an inability to grow and gain weight (failure to thrive). Difficulty swallowing (dysphagia) often lasts into adolescence. While muscle tone may improve over time, affected individuals usually have some weakness into adulthood. The weakness can lead to permanently bent joints (contractures) and abnormal curvature of the spine (scoliosis).

KCNK9 imprinting syndrome is also characterized by intellectual disability and delayed development of speech and motor skills, such as sitting and walking. Many affected individuals have limited speech throughout life.

This condition is associated with unusual facial features, including an elongated face that narrows at the temples; an upper lip that points outward (called a tented lip); a short, broad space between the lip and the nose (philtrum); a small lower jaw (micrognathia); and abnormally shaped eyebrows. Some affected individuals have an opening in the roof of the mouth (cleft palate). In addition to unusual facial features, some people with KCNK9 imprinting syndrome have a long neck, a narrow chest, and tapered fingers.  https://medlineplus.gov/genetics/condition/kcnk9-imprinting-syndrome

Clinical features

From HPO
Single transverse palmar crease
MedGen UID:
96108
Concept ID:
C0424731
Finding
The distal and proximal transverse palmar creases are merged into a single transverse palmar crease.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Microretrognathia
MedGen UID:
326907
Concept ID:
C1839546
Finding
A form of developmental hypoplasia of the mandible in which the mandible is mislocalised posteriorly.
Reduced subcutaneous adipose tissue
MedGen UID:
387876
Concept ID:
C1857657
Finding
A reduced amount of fat tissue in the lowest layer of the integument. This feature can be appreciated by a reduced skinfold thickness.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Long face
MedGen UID:
324419
Concept ID:
C1836047
Finding
Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective).
Narrow forehead
MedGen UID:
326956
Concept ID:
C1839758
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective).
Tented upper lip vermilion
MedGen UID:
326574
Concept ID:
C1839767
Finding
Triangular appearance of the oral aperture with the apex in the midpoint of the upper vermilion and the lower vermilion forming the base.
Short philtrum
MedGen UID:
350006
Concept ID:
C1861324
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD below the mean. Alternatively, an apparently decreased distance between nasal base and midline upper lip vermilion border.
Highly arched eyebrow
MedGen UID:
358357
Concept ID:
C1868571
Finding
Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape.
Submucous cleft soft palate
MedGen UID:
868770
Concept ID:
C4023175
Congenital Abnormality
A cleft of the muscular (soft) portion of the palate that is covered by mucous membrane. Soft-palate submucous clefts are characterized by a midline deficiency or lack of muscle tissue.
Bifid uvula
MedGen UID:
1646931
Concept ID:
C4551488
Congenital Abnormality
Uvula separated into two parts most easily seen at the tip.
Sacral dimple
MedGen UID:
98428
Concept ID:
C0426848
Finding
A cutaneous indentation resulting from tethering of the skin to underlying structures (bone) of the intergluteal cleft.
Long eyelashes
MedGen UID:
342955
Concept ID:
C1853738
Finding
Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective).

Recent clinical studies

Etiology

Hamilton MJ, Suri M
Adv Genet 2020;105:137-174. Epub 2020 May 26 doi: 10.1016/bs.adgen.2020.03.002. PMID: 32560786

Diagnosis

Yamada M, Suzuki H, Watanabe A, Uehara T, Takenouchi T, Mizuno S, Kosaki K
Congenit Anom (Kyoto) 2021 May;61(3):76-81. Epub 2020 Nov 24 doi: 10.1111/cga.12400. PMID: 33118233
Hamilton MJ, Suri M
Adv Genet 2020;105:137-174. Epub 2020 May 26 doi: 10.1016/bs.adgen.2020.03.002. PMID: 32560786
Graham JM Jr, Zadeh N, Kelley M, Tan ES, Liew W, Tan V, Deardorff MA, Wilson GN, Sagi-Dain L, Shalev SA
Am J Med Genet A 2016 Oct;170(10):2632-7. Epub 2016 May 6 doi: 10.1002/ajmg.a.37740. PMID: 27151206
Veale EL, Hassan M, Walsh Y, Al-Moubarak E, Mathie A
Mol Pharmacol 2014 Mar;85(3):397-407. Epub 2013 Dec 16 doi: 10.1124/mol.113.090530. PMID: 24342771

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