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. 2021 Dec 23;13(1):29.
doi: 10.3390/genes13010029.

Clinical and Genetic Findings in a Series of Eight Families with Arthrogryposis

Marzia Pollazzon  1 , Stefano Giuseppe Caraffi  1 , Silvia Faccioli  2   3 , Simonetta Rosato  1 , Heidi Fodstad  4 , Belinda Campos-Xavier  4 , Emanuele Soncini  5 , Giuseppina Comitini  6 , Daniele Frattini  7 , Teresa Grimaldi  8 , Maria Marinelli  1 , Davide Martorana  9 , Antonio Percesepe  9 , Silvia Sassi  2 , Carlo Fusco  7 , Giancarlo Gargano  10 , Andrea Superti-Furga  4 , Livia Garavelli  1
Affiliations

Clinical and Genetic Findings in a Series of Eight Families with Arthrogryposis

Marzia Pollazzon et al. Genes (Basel). .

Abstract

The term "arthrogryposis" is used to indicate multiple congenital contractures affecting two or more areas of the body. Arthrogryposis is the consequence of an impairment of embryofetal neuromuscular function and development. The causes of arthrogryposis are multiple, and in newborns, it is difficult to predict the molecular defect as well as the clinical evolution just based on clinical findings. We studied a consecutive series of 13 participants who had amyoplasia, distal arthrogryposis (DA), or syndromic forms of arthrogryposis with normal intellectual development and other motor abilities. The underlying pathogenic variants were identified in 11 out of 13 participants. Correlating the genotype with the clinical features indicated that prenatal findings were specific for DA; this was helpful to identify familial cases, but features were non-specific for the involved gene. Perinatal clinical findings were similar among the participants, except for amyoplasia. Dilatation of the aortic root led to the diagnosis of Loeys-Dietz syndrome (LDS) in one case. The phenotype of DA type 5D (DA5D) and Escobar syndrome became more characteristic at later ages due to more pronounced pterygia. Follow-up indicated that DA type 1 (DA1)/DA type 2B (DA2B) spectrum and LDS had a more favorable course than the other forms. Hand clenching and talipes equinovarus/rocker bottom foot showed an improvement in all participants, and adducted thumb resolved in all forms except in amyoplasia. The combination of clinical evaluation with Next Generation Sequencing (NGS) analysis in the newborn may allow for an early diagnosis and, particularly in the DAs, suggests a favorable prognosis.

Keywords: Escobar syndrome; amyoplasia; arthrogryposis; differential diagnosis; distal arthrogryposis; genetic testing; multiple pterygium syndrome (MPS); prognosis.

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Conflict of interest statement

All authors declare that there are no conflict of interest concerning this work.

Figures

Figure 1
Figure 1
Phenotypic characteristics of the participants. Family 1 (Red background: 1A–E pt 1; 2A–E pt 2; 3A–C pt 3). (1A) At birth. (1B–E) At 3 years and 8 months of age. (2A) In the neonatal period. (2B–E) At 24 years of age. (3A–C) At 48 years of age. Family 2 (Blue background: 4A–J pt 4; 5A–D pt 5; 6A–E pt 6). (4A–E) At birth. (4F–I) At 26 years of age. (5A–D) At 1 month of life. (6A–E) At 1 month of life. Family 3 (Yellow background: 7A–C pt 7; 8A–D pt 8). (7A–C) At 1 month of life. (8A–D) At 27 years of age. Family 4 (Green backgorund: 9A–K pt 9). (9A,B) In the neonatal period. (9C–G) At 7 years of age. (9H–K) At 12 years and 1 month. Family 5 (Magenta background: 10A–E pt 10). (10A) At birth. (10B–E) At 4 years and 9 months of age. Family 6 (Violet background: 11A–F pt 11). (11A,B) At birth. (11C–F) At 1 year and 7 months. Family 7 (Orange background: pt 12). (12A): Hands at 25 years of age. Family 8 (Cyan backgroun: 13A–F pt 13). (13A) In childhood. (13B–F) At 35 years of age.
Figure 1
Figure 1
Phenotypic characteristics of the participants. Family 1 (Red background: 1A–E pt 1; 2A–E pt 2; 3A–C pt 3). (1A) At birth. (1B–E) At 3 years and 8 months of age. (2A) In the neonatal period. (2B–E) At 24 years of age. (3A–C) At 48 years of age. Family 2 (Blue background: 4A–J pt 4; 5A–D pt 5; 6A–E pt 6). (4A–E) At birth. (4F–I) At 26 years of age. (5A–D) At 1 month of life. (6A–E) At 1 month of life. Family 3 (Yellow background: 7A–C pt 7; 8A–D pt 8). (7A–C) At 1 month of life. (8A–D) At 27 years of age. Family 4 (Green backgorund: 9A–K pt 9). (9A,B) In the neonatal period. (9C–G) At 7 years of age. (9H–K) At 12 years and 1 month. Family 5 (Magenta background: 10A–E pt 10). (10A) At birth. (10B–E) At 4 years and 9 months of age. Family 6 (Violet background: 11A–F pt 11). (11A,B) At birth. (11C–F) At 1 year and 7 months. Family 7 (Orange background: pt 12). (12A): Hands at 25 years of age. Family 8 (Cyan backgroun: 13A–F pt 13). (13A) In childhood. (13B–F) At 35 years of age.
Figure 1
Figure 1
Phenotypic characteristics of the participants. Family 1 (Red background: 1A–E pt 1; 2A–E pt 2; 3A–C pt 3). (1A) At birth. (1B–E) At 3 years and 8 months of age. (2A) In the neonatal period. (2B–E) At 24 years of age. (3A–C) At 48 years of age. Family 2 (Blue background: 4A–J pt 4; 5A–D pt 5; 6A–E pt 6). (4A–E) At birth. (4F–I) At 26 years of age. (5A–D) At 1 month of life. (6A–E) At 1 month of life. Family 3 (Yellow background: 7A–C pt 7; 8A–D pt 8). (7A–C) At 1 month of life. (8A–D) At 27 years of age. Family 4 (Green backgorund: 9A–K pt 9). (9A,B) In the neonatal period. (9C–G) At 7 years of age. (9H–K) At 12 years and 1 month. Family 5 (Magenta background: 10A–E pt 10). (10A) At birth. (10B–E) At 4 years and 9 months of age. Family 6 (Violet background: 11A–F pt 11). (11A,B) At birth. (11C–F) At 1 year and 7 months. Family 7 (Orange background: pt 12). (12A): Hands at 25 years of age. Family 8 (Cyan backgroun: 13A–F pt 13). (13A) In childhood. (13B–F) At 35 years of age.
Figure 2
Figure 2
Pedigrees of the reported families. Pt = participants. V = variant. wt = wild-type. TOP = Termination Of Pregnancy. CK = creatine kinase. The arrow indicates the index case in each family.
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